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Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types ( χ 2 =12.524, P =0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P <0.05). Among them, while in the patients with CNH type, the pathological grade was G 3 , the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P <0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P <0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis ( OR =5.884, 95% CI =0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis ( P =0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis ( OR =29.010, 95% CI : 2.067-407.173; P= 0.012). In the patients with CNL, myometrium infiltration depth≥1/2 ( OR =4.995, 95% CI : 1.225-20.376; P =0.025), lymphatic vascular space infiltration ( OR =14.577, 95% CI : 3.603-58.968; P <0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma ( OR =7.451, 95% CI : 1.127-49.281; P =0.037), cervical interstitial infiltration ( OR =22.938, 95% CI : 1.207-436.012; P =0.037), lymphatic vascular space infiltration ( OR =9.404, 95% CI : 1.609-54.969; P POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.

Objective: To investigate the molecular classification of endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) treated with fertility-sparing therapy, and to analyze its relationship with clinicopathological factors and treatment efficacy. Methods: A total of 46 EC and AEH patients who received fertility-sparing therapy and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2021, were retrospectively collected. The relationships between molecular classification and clinicopathological factors and treatment outcomes were analyzed. Results: (1) Of the 46 patients, including 40 EC and 6 AEH patients, 32 cases (71%, 32/45) had complete response (CR) after treatment, with median CR time of 8 months, 6 cases (13%, 6/45) had partial response, and 8 cases (25%, 8/32) had recurrence. (2) The cases were distributed as no specific molecular profile (NSMP) 34 cases (74%, 34/46) subtype mainly, high microsatellite instability (MSI-H) 7 cases (15%, 7/46), POLE ultra-mutated 3 cases (7%, 3/46), and copy number high (CNH) 2 cases (4%, 2/46). Patients with CNH had the hightest serum cancer antigen 125 (CA 125 ) level [(34.3±35.2) kU/L]. MSI-H subtype had more family history of tumors (6/7), more with loss of mismatch repair (MMR) protein expression by immunohistochemical (7/7), and higher nuclear antigen associated with cell proliferation (Ki-67) expression level (3/3). (3) Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6; P =0.019), and survival analysis showed that they were less likely to achieve CR than those with NSMP subtype ( P =0.022). Subgroup analysis of patients with NSMP showed that age ≥30 years related with longer treatment time to CR ( P =0.010). In addition, CR was obtained after treatment in 2/3 POLE ultra-mutated cases and 2/2 CNH, respectively. Conclusions: Molecular classification relates with the treatment response in patients with EC and AEH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy, and patients with NSMP need to be further studied and predict treatment benefit. However, there are few cases in POLE ultra-mutated and CNH subtypes, which need further clinical research.

Objective: To investigate the clinical and immunological characteristics of overlap myositis (OM) patients., Methods: The data of 368 patients with idiopathic inflammatory myopathies (IIMs) admitted to Peking University People's Hospital from January 2004 to August 2020 were analyzed retrospectively, including demographic characteristics, clinical characteristics (including fever, Gottron' s sign/papules, Heliotrope rash, V-sign, Shawl sign, Mechanic' s hands, skin ulceration, periungual erythema, subcutaneous calcinosis, dysphagia, myalgia, myasthenia, arthritis, Raynaud' s phenomenon, interstitial lung disease, pulmonary hypertension and myocardial involvement), laboratory characteristics, immunological characteristics [including antinuclear antibodies, rheumatoid factors, myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs)] and survival. The clinical and immunological characteristics and prognostic differences of OM and non-OM were compared. The Kaplan-Meier and Log Rank methods were used to analyze the survival., Results: A total of 368 patients were included. 23.9% (88/368) of IIMs patients were OM patients. Among the 88 OM patients, 85.2% (75/88) of them were female, and the median interval between disease onset and diagnosis was 13.5 months. The incidence of overlapped connective tissue diseases in the OM patients was dermatomyositis (DM) in 60.2%, polymyositis (PM) in 3.4%, immune-mediated necrotizing myopathy (IMNM) in 2.3% and anti-synthetase syndrome (ASS) in 34.1%. Compared with the non-OM patients, the proportion of the females in the OM patients was higher (85.2% vs. 72.1%, P =0.016), the OM patients had longer disease duration [13.5(4.5, 48.0) months vs . 4.0(2.0, 12.0) months, P < 0.001]. As for clinical characteristics, compared with the non-OM patients, the incidence of V-sign (25.0% vs . 44.6%, P =0.001) and periungual erythema (8.0% vs . 19.6%, P =0.013) were lower; the incidence of Raynaud's phenomenon (14.8% vs . 1.8%, P < 0.001), interstitial pneumonia (88.6% vs . 72.1%, P =0.001), pulmonary hypertension (22.7% vs . 7.5%, P < 0.001) and myocardial involvement (18.2% vs . 9.3%, P =0.033) were higher. As for immunological characteristics, compared with the non-OM patients, the incidence of elevated aspartate aminotransferase (AST) (31.8% vs . 45.0%, P =0.035) was lower and elevated C-reactive protein (CRP) (58.0% vs . 44.6%, P =0.037) was higher; the positive rates of antinuclear antibodies (ANA) (85.1% vs . 63.4%, P =0.001) and rheumatoid factors (RF) (40.2% vs . 17.8%, P < 0.001) and anti-Ro-52 (71.6% vs. 56.1%, P =0.038) in serum were higher. There was no significant difference in the survival between the OM patients and non-OM patients., Conclusion: Pulmonary hypertension and myocardial involvement were frequently observed in OM.

Objective: To investigate the clinicopathological, immunohistochemical and molecular features of small round cell sarcoma (SRCS) of the bone and soft tissue, and to compare the diagnostic value of different techniques. Methods: Seventy-two cases of SRCS of the bone and soft tissue diagnosed at People's Hospital, Peking University from January 2016 to March 2020 were recruited and retrospectively analyzed for pathological morphology, immunophenotype and fluorescence in situ hybridization (FISH) data. Next generation sequencing (NGS) was performed on 13 difficult cases. Results: In the study cohort, the patients ranged in age from 4-55 years, with a male predominance. The most Ewing's sarcomas and osteosarcomas occurred in the bone, while CIC-rearranged sarcomas, BCOR-rearranged sarcoma, synovial sarcoma, extraskeletal myxoid chondrosarcoma and FUS-NFATc2 rearranged sarcoma occurred in soft tissue. Histologically, all cases were composed predominantly of small round cells. Most cases were positive for vimentin and CD99, and showed a variable reactivity for neurogenic markers. Muscle marker and epithelial marker were negative for most cases. Combined with clinical features, histopathologic findings, immunophenotype, FISH and NGS, we diagnosed 46 Ewing sarcomas, 14 osteosarcomas, 3 CIC-rearranged sarcomas, 1 BCOR-rearranged sarcoma, 1 synovial sarcoma, 1 clear cell soft tissue sarcoma, 1 extraskeletal myxoid chondrosarcoma, 1 FUS-NFATc2 rearranged sarcoma, and 4 undifferentiated small round cell sarcomas. Conclusions: SRCS of bone and soft tissue is a group of malignant mesenchymal tumors based on morphological features. Most cases can be diagnosed with a combination of clinical characteristics, morphological features and immunohistochemical phenotype, while some cases require such further tests as FISH and NGS technologies, and NGS can be useful in diagnosing and categorizing SRCS.

Objectives: To investigate the value of histopathological growth patterns (HGP) in predicting the 3-year progression free survival (PFS) after resection the liver metastasis from patients with colorectal cancer. Methods: The clinicopathological data of the 111 patients with liver metastasis of colorectal cancer diagnosed at Peking University People's Hospital, Beijing, China from January 2007 to January 2017 were analyzed. After excluding the patients who did not meet the inclusion criteria, a total of 80 patients were analyzed. According to the international expert consensus on HGP, the HGP types of liver metastasis were evaluated. The correlation between HGP and other clinicopathological factors was analyzed using χ 2 or Fisher test. Kaplan-Meier survival curve was used to examine 3-year PFS in the patients with liver metastasis of colorectal cancer by HGP. The independent risk factors of 3-year post-resection PFS were determined using univariable and multivariable analyses. Results: A total of 80 cases were analyzed, including 43 cases of desmoplastic type (54%), 32 cases of replacement type (40%), 3 cases of pushing type (4%), and 2 cases of mixed type (2%). There was no correlation of HGP with age, gender, time of metastasis, tumor burden, histological grade, mucous differentiation or microsatellite instability. The 3-year post-resection PFS of the patients with desmoplastic type was significantly longer than that of patients with replacement type. The univariable and multivariable analyses showed that HGP was an independent prognostic factor. Conclusions: The HGP of colorectal cancer metastases to the liver mainly present as desmoplastic and replacement types. HGP is an independent prognostic factor for the patients with liver metastasis of colorectal cancer after resection of the metastasis. Therefore, HGP should be clearly indicated in the pathological report to help guide clinical treatments.

Objective: To investigate the efficacy and pregnancy outcome of fertility-preserving treatment for patients with stage Ⅰa, grade 2 endometrial cancer (EC). Methods: Clinical data was retrospectively collected for EC or atypical endometrial hyperplasia (AEH) patients treated in Peking University People's Hospital, Foshan First People's Hospital of Guangdong Province and First Affiliated Hospital of Sun Yat-sen University, from 2010 to 2019. Inclusion criteria for fertility-preserving treatment included: (1) Age ≤45 years. (2) EC with histological differentiation of G(1), G(2) or endometrial AEH. (3) EC disease should be stage Ⅰa, confined to the endometrium without myometrial invasion, lymph node or extrauterine metastasis. Treatment regimen: patients were given oral progestin therapy and endometrial pathology was evaluated every three months. Patients were divided into three groups as G(2) EC group, G(1) EC group and AEH group based on the histological differentiation. Oncological and pregnancy outcomes were compared among them. Results: (1) Totally 57 eligible patients were included in this study, including 11 cases with G(2) EC, 22 cases with G(1) EC, and 24 cases with AEH. (2) Oncological outcome: among the three groups of G(2) EC, G(1) EC and AH, the complete remission rates (9/11, 91% and 96%, respectively) and recurrence rates (3/9, 30% and 22%, respectively) were not significantly different (all P >0.05). Median remission time was significantly longer in the G(2) EC group than those in the other two groups (8, 6 and 4 months; P =0.046). Among 9 G(2) EC patients who recurred after complete remission, three patients relapsed at 7, 18 and 53 months, respectively. All 3 patients chose fertility-sparing treatment again, and all achieved complete remission after retreatment. (3) Pregnancy outcome: among the three groups, the assisted reproduction technology rates (4/8, 5/18 and 36%, respectively) and pregnancy rates (6/8, 5/18 and 36%, respectively) had no significant difference ( P >0.05). However, time interval to pregnancy was shorter in G(2) EC patientsthan the other two groups (4, 9 and 22 months, respectively; P =0.006). Conclusions: Fertility-preserving treatment for patients with stageⅠa, G(2) endometrial cancer, may obtain a relatively high remission rate and an acceptable pregnancy rate. However, further exploration is needed due to the limited number of cases.

Objective: To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC). Methods: A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People's Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC. Results: The peak patients' age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group ( P< 0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion ( P< 0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without ( P< 0.05). There was no significant correlation between lymph node metastasis of PTMC and patients' gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion: As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.

Objective: To study the clinicopathological features, diagnosis and differential diagnosis of myeloid sarcoma of the breast. Methods: Ten cases of myeloid sarcoma (MS) and 19 cases of diffuse large B cell lymphoma (DLBCL) of the breast were selected from Peking University People's Hospital from February 2005 to September 2019. The cases were evaluated by microscopy and immunohistochemistry basing on WHO classification (2008 and 2017). Results: For the 10 cases of MS, the mean and median age was 33.8 and 31 years (range 23 to 47 years) respectively. All patients presented with breast masses; six presented with B symptoms (6/10); and LDH level was elevated in four patients. The largest tumor dimension was 1.0 to 5.3 cm (mean 2.7 cm). All 10 patients had history of acute myeloid leukemia (AML), and in one patient, the AML occurred after chemotherapy for hydatidiform mole. One case was classified as M0, four were M2, two were M4 and three were M5. For the AML, all patients received chemotherapy and nine were treated by allogeneic hematopoietic stem cell transplant (allo-HSCT) and the breast masses occurred4 months to 2 years post-transplant. Using Ann Arbor staging, five cases were stage Ⅰ, three were stage Ⅱ, and 2 were stage Ⅳ. The MS was found in the left breast (two cases); right breast (three cases) and both breasts (five cases). Lymphocyte in peripheral blood, B symptom and site of lesion had statistical significance between myeloid sarcoma and DLBCL( P <0.05). The tumor cells were primitive, expressing MPO, CD43, CD117, etc. All ten patients had follow-up information, and the median survival period was 14.4 months (range 1 to 50 months). Seven patients died. The prognosis of patients with MS was worse than DLBCL( P =0.002). Conclusions: The clinical history, pathologic morphology, immunophenotyping and molecular studies are very important for diagnosing MS tumors in the breast, and MS may occur after allo-HSCT for AML. Tumor resection, chemotherapy, radiotherapy and donor lymphocyte infusion are recommended for treatment. The prognosis is poor.

Objective: To summarize the clinical characteristics of patients misdiagnosed with IgG4-related disease, to analyze the reasons of misdiagnosis and to improve the clinical recognition of the disease., Methods: The general data, clinical manifestations, laboratory examination results and pathological features of 17 patients with IgG4-related diseases misdiagnosed outside the hospital were retrospectively analyzed., Results: Among the 17 patients, there were 9 males and 8 females with a median age of 45 years, and the median time from onset to diagnosis was 12 months. Most patients' initial admission department was not rheumatology or immunology department. Six of the 17 patients were eventually diagnosed with lymphoproliferative disease, 4 with autoimmune disease, and 2 with infectious disease, Rosai Doffman disease, desmofibromatosis, highly differentiated mucoepidermoid carcinoma of the bottom of the mouth, hypereosinophilic syndrome, asthma and allergic rhinitis in 1 case each. The typical sites of IgG4-related disease were involved in 14 patients, including 6 cases of parotid gland, 2 cases of submandibular gland, 3 cases of pancreas and 2 cases of retroperitoneal lesions. Serum IgG4 was elevated in 10 patients, serum IgG4/IgG value was higher than 10% in 7 patients, serum IgE was increased in 7 patients, complement was decreased in 4 patients, and eosinophilic granulocytes were increased in 3 patients. Pathological biopsy was performed in 15 patients, and infiltration of lymphocyte was observed in 10 patients, IgG4+ plasma cells were present in 5 patients, the ratio of IgG4+ plasma cells to IgG+ plasma cells was less than 40% in 4 patients and greater than 40% in 1 patient. However, none of the 15 patients had the storiform pattern of fibrosis and obliterative phlebitis., Conclusion: A variety of diseases can perform as IgG4-related disease witih typical sites involved, elevated serum IgG4, even can be characterized by pathological IgG4+ plasma cells infiltration. Physicians should pay attention to the differential diagnosis and comprehensively evaluate the patient's clinical manifestations, and laboratory results. Timely and even repeated pathological biopsy is also needed for definite diagnosis.

Objective: To investigate the clinicopathological characteristics and significance of solid, endometrioid and transitional (SET) ovarian high-grade serous carcinoma (HGSC). Methods: A total of 408 cases of ovarian HGSC admitted to Peking University People's Hospital from January 2011 to September 2016 were collected. (1) According to the proportion of tumors with SET form in all tumors, they were divided into three groups: HGSC-classic group (<25%), HGSC-SET Ⅰ (25%-50%) and HGSC-SET Ⅱ (>50%) group. The clinical and pathological characteristics of three groups of ovarian HGSC patients were compared respectively. (2) According to the growth pattern, that was, the proportion of pushing/expanding invasive tumors in the whole pelvic disseminated tumors of pelvic disseminated tumors, the three groups were divided into four subgroups: group A (0-25%), group B (26%-50%), group C (51%-75%) and group D (>75%). Differences in progression-free survival (PFS) among the four subgroups in each group were compared respectively. Results: The median age of 408 cases with ovarian HGSC was 63.3 years (47-78 years), including 152 cases premenopausal and 256 cases postmenopausal. Among 408 cases of ovarian HGSC, 290 cases were in HGSC-classic group, 91 cases in HGSC-SET Ⅰ and 27 cases in HGSC-SET Ⅱ group. (1) There were significant differences in age, proportion of menopausal patients, tumor necrosis (including map necrosis or acne necrosis), response rate to primary chemotherapy, 5-year mortality rate and PFS between HGSC-SET Ⅰ and HGSC-SET Ⅱ ( P <0.05). There was no significant difference among the above indexes between HGSC-SET Ⅰ and HGSC-SET Ⅱ ( P >0.05). In HGSC-classic group, HGSC-SET Ⅰ and HGSC-SET Ⅱ, the proportion of family members or patients with history of epithelial ovarian cancer or breast cancer increased in turn, and the detection rate of serous tutal intraepithelial carcinoma (STIC) in fallopian tube tissue decreased in turn. There were significant differences between the two groups ( P <0.05). (2) In HGSC-classic group, there were 147 cases in group A, 124 cases in group B and 19 cases in group C (0 case in group D), with median PFS of 17.4, 17.7 and 16.5 months respectively ( P <0.05); 10, 6, 29 and 46 cases in group A, B, C and D in HGSC-SET Ⅰ, with median PFS of 9.6, 12.7, 30.1 months and 39.0 months respectively, which there were significant difference among group A and C and D (all P <0.05); among group B, C and D group in HGSC-SET Ⅱ, there were respectively 3, 12 and 12 cases (0 case in group A), and the median PFS was 13.5, 34.2 and 47.8 months ( P <0.05). PFS was positively correlated with the increase of push/expansive infiltration ratio. Conclusions: The detection rate of STIC in ovarian HGSC patients with SET is higher, the effect of primary chemotherapy is better, and PFS is prolonged. PFS was significantly prolonged in patients with pelvic disseminated tumors of HGSC-SET, the infiltration of which were predominated by pushing or expanding boarder.

Objective: To investigate the expression of immunomarkers CK7, CK20, CK17, CDX2, MUC1 and MUC2 in primary adenocarcinoma of the ampulla of Vater, to explore the role of these markers in the histopathologic subclassification of ampullary carcinoma; and to provide biologic basis for precision treatment of patients with different types of ampullary carcinoma. Methods: Forty-two cases of primary ampullary carcinoma were collected at Peking University People's Hospital, from 2012 to 2018 year. There were 22 males and 20 females. Aged range 42 to 88 years old, with mean aged (62±11) years. Among the patients, 6 was high differentiation, 19 median differentiation, and 17 low differentiation. Immunohistochemical studies on the expression of CK7, CK20, CK17, CDX2, MUC1 and MUC2 were performed in 42 cases of primary ampullary carcinoma. The relationship between different ampullary carcinoma subtypes and clinicopathologic survival data was analyzed using SPSS 16.0 statistical software. Results: Three histopathologic subtypes were observed. Among 42 cases, 8(19.0%)were classified as intestinal subtype, which showed a positive expression rate of 8/8 for both CK20 and CDX2, and 5/8 for MUC2. Both CK7 and CK17 were weakly expressed in one case (1/8). No expression was observed for MUC1 in this subtype. Twenty-two (52.4%,22/42) cases were classified as pancreaticobiliary subtype, which showed a positive expression rate of 100.0%(22/22) for both CK7 and MUC1, and 90.9% (20/22) for CK17. No expression was observed for CK20, CDX2 and MUC2.The remaining 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns. The expression frequencies of these 6 immunomarkers in different subtypes of ampullary carcinoma did not correlate with various clinicopathologic factors such as patient gender and age, tumor size, histologic differentiation, pancreatic and bile duct invasion, or the depth of duodenal invasion. However, stage Ⅲ+Ⅳ diseases were more commonly seen in pancreaticobiliary type (63.6%,14/22) than intestinal type (2/8) and mixed type (3/9; χ(2)=6.508, P= 0.039). Follow-up data showed a trend of better survival rate for patients with intestinal subtype than those with mixed and pancreaticobiliary subtypes. Conclusions: Ampullary carcinoma can be subclassified into three different subtypes using a panel of six immunomarkers, especially for the identification of subtypes of poorly differentiated carcinoma. CK7, CK17 and MUC1 are major markers of pancreaticobiliary subtype, whereas CK20, CDX2 and MUC2 are useful markers for intestinal subtype. The mixed subtype variably expresses these markers. The prognosis of patients with intestinal subtype appears better than that of pancreaticobiliary and mixed subtypes. Accurate subtyping of ampullary carcinoma is clinically important to patient management and prognosis assessment.

Objective: To assess the clinical value for the clinicopathological features of microcystic elongated and fragmented (MELF) invasion in endometrial carcinoma (EEC) . Methods: The clinicopathological data of 108 cases of endometrial carcinoma with total hysterectomy, bilateral adnexectomy, and pelvic dissection were retrospectively analysis in Peking University People's Hospital from April 2015 to October 2016. Twenty-five patients with endometrial carcinoma showing MELF invasion pattern were collected. We analyzed retrospectively the association of MELF pattern invasion with clinical pathology data and prognosis of the patients, partial immunohistochemical staining was implemented. MELF invasion was a special invasion pattern and characterized by microcystic, elongated, fragmented (composed of cluster cells) gland in muscular layer. Results: The incidence rate was 23.1% (25/108). These patients mean age was (59.3±10.9) years old. Four cases were premenopausal, and 21 were postmenopausal. Abnormal vaginal bleeding was the main clinical presentation. The lesions tend to appear adjacent to the tumor body. Sometimes, it may be appears away from the tumor body in the deep muscle layer.Lymph node metastasis were present in 5 cases (20%, 5/25). Thirteen cases (52%, 13/25) of them demonstrated lymph vascular space involvement (LVSI). The immunohischemical expression of ER,PR, Ki-67 and galectin-3 showing MELF invasion pattern were weaker than no showing MELF invasion pattern endometrial carcinoma, cktokeratin (CK) was showed diffuse strong positive expression, E-cadherin was moderately positive expression. All 25 cases were followed up for (23.2±5.9) months (14-33 months) after the therapy with no recurrence on metastasis. Conclusions: MELF invasion pattern is a special invasion pattern in low-grade EEC. The incidence of LVSI and lymph node metastasis rate in endometrial carcinoma with MELF invasion are significantly increased. The prognosis of MELF invasion pattern may be poor.

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of tumors of haematopoietic and lymphoid tissue in the female productive tract. Methods: Eleven cases of myeloid sarcoma and leukemia, 9 of non Hodgkin lymphoma (NHL) , 13 of cervical lymphoma-like lesions were selected from Peking University People's Hospital from January 2006 to August 2017. According to WHO classification of tumors of haematopoietic and lymphoid tissues (2008) and updated classification(2016), the cases were studied by microscopy, immunohistochemistry and in situ hybridization. Results: In 20 cases of tumors of haematopoietic and lymphoid tissue, the mean and median age was 48.5 and 56 years old (range: 16-77 years old) . In cases of lymphoma-like lesion of uterine cervix, the mean and median age was 45.9 and 48 years old (range: 23-62 years old) . The patients with neoplasm present as fever, fatigue, hypogastralgia, colporrhagia and mass etc. Eight cases had history of acute myeloid leukemia, and 3 had myeloid leukemia while pregnancy. One case of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) had history of ovary small cell carcinoma and high grade serous carcinoma resected with chemotherapy. One case of diffuse large B cell lymphoma (DLBCL) had history of renal transplantation. Lactic dehydrogenase (LDH) was elevated in 9 cases (9/18) . The cases of lymphoma-like lesion present as contact bleeding in most cases and all located in cervix. Four cases of neoplasm located in vulva, 1 in vagina, 4 in cervix, 4 in uterine corpus, 8 in ovary and 2 in placenta. Clinical staging of NHL: 4 case was stageⅠ, 1 case of stageⅢ, and 4 cases of stage Ⅳ. Pathological morphology: 9 cases were myeloid sarcoma, 2 cases were placenta invaded by myeloid leukemia. Six cases were DLBCL, and 1 case was CLL/SLL, 1 case was mucosa associated lymphoid tissuse lymphoma (MALToma) , and 1 case was anaplastic large cell lymphoma. Resected mass, chemotherapy was performed in tumors of haematopoietic and lymphoid tissue. Five cases of myeloid sarcoma and 2 of NHL died. In 13 cases of lymphoma-like lesion of uterine cervix, the general condition was good as following up. Conclusions: The clinical history, pathological morphology and immunohistochemistry are very important for diagnosing tumors of haematopoietic and lymphoid tissue in the female productive tract. Resection with chemotherapy is recommended in treatment. The prognosis of lymphoma-like lesion of uterine cervix is good, and should be differentiated from lymphoma.

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of the tumors of lymphoidand hematopoietic tissue of the spleen(TLTS). Methods: Fifty-three cases of TLTS were selected from the pathologic files from Peking University People's Hospital from April 2002 to April 2017. According to WHO classification of tumors of hematopoietic and lymphoid tissues (2008) and its updated classification (2016), the cases were studied by microscopy, immunohistochemistry and in situ hybridization, combined with the bone marrow biopsy and clinical examination. Results: In 53 cases of TLTS, the male to female ratio was 3.4∶1.0; the mean age was 55.4 years (range 21-76 years), and all patients presented with variable degree of splenomegaly. Laboratory examination showed increased percentage of lymphocyte in peripheral blood in 22 cases, and elevated serum LDH level in 24 cases. Abnormal blood counts were seen in 26 cases pre-operatively, in which 22 cases showed complete or partial correction of these abnormalities post-operatively (84.6%, 22/26). The clinical symptoms included abdominal pain or distension, fatigue, fever, and weight loss, etc. Seventeen cases presented with lymphadenopathy of abdomen or other sites. Bone marrow biopsy was performed in 30 cases, and 19 cases were involved by tumor (63.3%). Of all 53 cases, 43 were diagnosed as primary splenic lymphoma (PSL), and the remaining 10 cases as secondary TLTS. According to Ann Arbor staging, 14 cases were stages Ⅰ or Ⅱ, 6 were stage Ⅲ and 28 were stage Ⅳ. By histopathologic classification, 43 cases of PSL were splenic B-cell marginal zone lymphoma (SMZL; 48.8%, 21/43), diffuse large B cell lymphoma (DLBCL; 23.3%, 10/43), splenic diffuse red pulp small B-cell lymphoma (11.6%, 5/43), mantle cell lymphoma (9.3%, 4/43), follicular lymphoma (4.7%, 2/43), and composite lymphoma (CL, DLBCL and classical Hodgkin lymphoma; 2.3%, 1/43). The remaining 10 cases were chronic lymphocytic leukaemia/small lymphocytic lymphoma (4 cases), hairy cell leukaemia (1 case), hepatosplenic T-cell lymphoma (HSTL; 5 cases), with lesions in other sites. Of the 53 cases of TLTS, 47 were B cell neoplasm (88.7%, 47/53), and the T cell neoplasms were all HSTL(5 cases, 9.4%, 5/53), 1 case was composite lymphoma. In 11 cases of TLTS, EBER in situ hybridization was performed and all cases were negative. Forty eight cases had follow-up data, and the median survival period was 17.0 months(range: 1-96 months). The survival of patients with SMZL and DLBCL were 25.7 and 18.6 months respectively. Thirteen patients died (27.1%, 13/48). The prognosis of those with elevated LDH level, high clinical stage, B symptoms and older than 60 years of age was worse. And the prognosis of DLBCL was worse than that of SMZL. There was no statistically significant difference between these factors and prognosis ( P >0.05). Conclusions: Most TLTS cases present with splenomegaly and abnormal blood counts, and complete or partial remission of blood counts isseen after splenectomy. The most common pathologic types of TLTS are SMZL and DLBCL. Definite diagnosis of TLTS could be made by combining clinical features, histopathology, immunophenotype, genetics, bone marrow biopsy and laboratory examination.

Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) combined with bronchial brushing cytology for detecting lung cancer. Methods: Centromeric enumeration probes (CEPs) for chromosomes 7, 8 and 17 were used in FISH assay. The combination of FISH and cytology was analyzed in 69 bronchial brushing specimens. Results: The positive rates of CEP7, CEP8 and CEP17 in malignant cases diagnosed by cytology were 50.0%, 80.8% and 65.4%, respectively. CEP8 probe showed significantly higher positive rate than CEP7 ( P =0.015). In the samples of suspicious of malignancy, the positive rates of CEP7, CEP8 and CEP17 were 46.6%, 66.7% and 58.8%, respectively. While in atypical cases, the positive rates of these three probes were 20.0%, 33.3% and 25.0%, respectively. There was no statistical difference between suspicious of malignancy and atypical cases ( P >0.05) as well as between malignant and suspicious of malignancy ( P >0.05). No chromosome aberrations were found in normal cases diagnosed by cytology. The positive rates of these three probes in adenocarcinoma (ADC) were slightly higher than those in squamous cell carcinoma and small cell lung cancer. However, only CEP8 probe showed statistically difference between ADC and small cell lung cancer ( P =0.044). The combination of cytology and FISH using any one of the three-probe set (CEP7, CEP8 and CEP17) showed the sensitivity and specificity of 80.3% and 100.0%, while those of cytology were 54.1% and 100.0%, respectively. Conclusions: FISH combined with cytomorphology assisted the cytology diagnosis of suspicious of malignancy and atypical cases. Therefore, it significantly improved the diagnostic sensitivity for lung cancer without sacrificing specificity.

Aims: To evaluate the sampling adequacy and diagnostic accuracy of the endometrial SAP-l sampling device in detecting endometrial lesions based on histopathological examination., Materials and Methods: In total, 182 patients who required an endometrial biopsy were enrolled in this study. All of the patients underwent endometrial biopsies with the SAP-l sampler prior to hysteroscopy (169/182) or dilatation and curettage (D&C) (13/182). Endometrial tissues were obtained at biopsy for histopathological examination., Results: Ad- equate endometrial specimens were obtained in 148 of 182 patients (81.32%). Menopause (p = 0.000), endometrial thickness (p = 0.004), and the types of endometrial diseases (p = 0.009) differed significantly between the two groups. Among the 169 patients who underwent hysteroscopy, sampling scratches were observed in the uterine cavity in 147 cases (86.98%). Compared to traditional methods, such as hysteroscopy and D&C, the sampling diagnostic sensitivity, specificity, and positive and negative predictive values were 82.35%, 100%, 100% , and 97.76% for endometrial carcinoma (n=17) and 37.5%, 100%, 100% and 97.76% for endometrial atypical hyperplasia (n=8), respectively. Those that were misdiagnosed occurred because the lesions were focal or localized in a small part of the uterine cavity. The sampling diagnostic sensitivity for polyps (n=32) was 12.5%. Two patients with submucosal leiomyoma went undiagnosed based on the sample specimens., Conclusion: Endometrial sampling using the SAP-l sampler is a minimally invasive altemative technique for obtaining adequate endometrial specimens for histopathological examination. The SAP-l sampler was useful in detecting endometrial carcinoma and atypical hyperplasia cases that were not highly suspected to be localized; however, this method was not useful in detecting endometrial polyps and submucosal leiomyomas.

Objective: To assess the changing trends in Gleason score (GS) of Chinese prostate carcinoma (PCa) from January 1995 to December 2014., Methods: In the study, 875 patients admitted to hospital from January 1995 to December 2004 (1995-2004) and from January 2005 to December 2014 (2005-2014) were divided into two groups. The mean levels and proportions of GS, primary and secondary grades were studied. The patients were divided into four groups according to age: <60, 60-69, 70-79 and ≥80 years. Types of specimen included needle biopsy (NB), transurethral resection of the prostate (TURP) and radical prostatectomy (RP). Histological types were made up by acinar carcinoma and other types (including atrophic, pseudohyperplastic, foam, signet ring cell and ductal carcinoma, and so on). The total prostate-specific antigen (tPSA) involved groups of <20.0 μg/L and ≥20.0 μg/L. We observed the mean levels and proportions of GS in age, types of specimen, histological types and total prostate-specific antigen in different periods, and used SPSS 17.0 software for statistical analysis., Results: Compared with 1995-2004, the mean levels of GS, primary and secondary grades decreased 0.32 (P=0.003), 0.19 (P=0.001) and 0.12 (P=0.016) in 2005-2014, respectively. The proportions of ≤6 in GS increased 10.9% (P=0.003), and ≥8 decreased 14.0% (P<0.001). The difference of GS 7 was not statistically significant. In the primary grade, the ratio of grades≤3 increased 12.8% (P=0.001), and grade 4 decreased 7.4% (P=0.037), grade 5 decreased 5.5% (P=0.007). The ratio of secondary grades ≤3 increased 7.6% (P=0.037). The difference of grades 4 and 5 was not statistically significant., Conclusion: GS in Chinese patients with PCa showed a downward trend, which is one of the notable features in the past 20 years in China. The types of specimen and age are important factors in GS, while the histological types and tPSA have less impact on the GS.

Pheochromocytoma is rare in pregn'ancy. Clinical features of a case of pheochromocytoma during pregnancy in the Peking University People's Hospital was investigated and the literature reviewed to discuss the diagnosis and treatment of this disease. The patient manifested with hypertension and proteinuria, who was easily misdiagnosed with gestational hypertension disease. When she was transferred to our hospital, the symptoms such as, paroxysmal palpitation, dizziness, vomiting were noticed, and the possibility of pheochromocytoma was considered due to the accompanying abdominal mass. An emergent cesarean section was performed successfully due to preterm labor during the treatment of the disease. After the delivery the drug preparation continued. And the laparoscopic resection of pheochromocytoma proceeded when the blood pressure was steady. The patient recovered fully after the surgery. The final diagnosis of pheochromocytoma was confirmed with the pathology. Its diagnosis and treatment experiences could improve our understanding and treatment of secondary hypertension due to pheochromocytoma in pregnancy.

Objective: To evaluate the potential benefits of systemic pelvic and para-aortic lymphadenectomy in endometrioid uterine cancer patients., Methods: We conducted a retrospective study on 244 cases of endometrioid uterine cancer that involved surgery in the Center of Gynecologic Oncology, Peking University People's Hospital, Beijing, from January 2000 to May 2008. We conducted staging for each case to ensure accordance with FIGO 2009 surgical staging criteria. Clinical data, including histology, age at diagnosis, surgical procedure, adjuvant therapy, date of death or last follow-up, and date and sites of recurrence were collected for each patient., Results: Among 244 endometrioid uterine cancer patients, 207 cases (84.8%) underwent systemic pelvic lymphadenectomy. Among these cases, pelvic lymph nodes in 17 cases (8.2%) exhibited tumor metastasis. Systemic aortic lymphadenectomy was performed in 127 cases (52.0%) among 244 total patients. Five cases (3.9%) exhibited positive aortic lymph nodes, of which four exhibited positive pelvic lymph nodes. We investigated the impact of positive retroperitoneal lymph nodes on staging: 4 (4/161, 2.5%), 6 (6/29, 20.7%), 6 (6/35, 17.1%), 1 (1/8) and 1 (1/6) case changed to stage IIIc from stage Ia, Ib, II, IIIa, and IIIb, respectively. Tumor-free and overall survival did not differ between patients who underwent pelvic lymphadenectomy or not (P > 0.05). Tumor-free survival improved in stage Ib pelvic lymphadenectomy patients (P = 0.040); para-aortic lymphadenectomy did not improve patient survival in all stages (P > 0.05)., Conclusion: Systemic lymphadenectomy is not warranted in stage Ia endometrioid uterine cancer., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

To study the effects of excision repair cross-complementing 1 (ERCC1) on the pathophysiological process of brain ischemia, we examined the changes in ERCC1 expression, as well as the functional significance of ERCC1 in the rat brain following middle cerebral artery occlusion (MCAO). The results were as follows: (1) ERCC1 immunopositive cells were widely distributed in various brain regions. ERCC1 expression was localized to the nuclei of neurons and astrocytes. (2) ERCC1 expression, as determined by western blot, increased at 3 days, remaining until 14 days, in the ipsilateral cortex and striatum following MCAO. Immunohistochemical analysis demonstrated that ischemia induced increased ERCC1 expression within the periinfarct core, with increasingly less expression toward the core. (3) Knockdown of ERCC1 expression by intraventricular injection of antisense plasmids increased DNA damage and infarct volume in the ischemic brain. (4) ERCC1 overproduction, by injection of expression plasmids, significantly reduced infarct volume and the accumulation of DNA-damaged neurons. Taken together, these results indicate that both endogenous ERCC1 and exogenous ERCC1 have an important neuroprotective function in the brain. In addition, administration of ERCC1 to the brain could prove to be a successful strategy for neuronal protection against ischemic injury.

Aims: To investigate p63 expression in ovarian neoplasms., Methods and Results: Immunohistochemistry using an antibody that detects all p63 isoforms was performed on 103 primary ovarian neoplasms of different histological types. Diffuse nuclear immunoreactivity of p63 was demonstrated in the 17 benign and five borderline Brenner tumours. Only one of the six malignant Brenner tumours displayed p63 expression. p63 immunoreactivity was absent in all the ovarian transitional cell carcinomas (TCC), but was demonstrated extensively in TCCs of the urinary bladder. Besides focal p63 expression in epidermal basal cells of immature and mature teratomas, all other ovarian lesions were devoid of p63 expression. p63 expression was also demonstrated in cervical transitional cell metaplasia and Walthard cell nests of fallopian tubes., Conclusions: Expression of p63 protein is apparently cell lineage specific and in ovarian neoplasms is confined to benign and borderline Brenner tumours. The loss of expression in malignant Benner tumours suggests a role for p63 in Brenner carcinogenesis. The distinct patterns of p63 expression in TCCs in the ovary and urinary bladder may help in their differential diagnosis.

The sodium iodide symporter (NIS) mediates iodide uptake into thyrocytes and is the molecular basis of thyroid radioiodine therapy. We previously have shown that NIS gene transfer into the F98 rat gliomas facilitated tumor imaging and increased survival by radioiodine. In this study, we show that: (1) the therapeutic effectiveness of (131)I in prolonging the survival time of rats bearing F98/hNIS gliomas is dose- and treatment-time-dependent; (2) the number of remaining NIS-expressing tumor cells decreased greatly in RG2/hNIS gliomas post (131)I treatment and was inversely related to survival time; (3) 8 mCi each of (125)I/(131)I is as effective as 16 mCi (131)I alone, despite a smaller tumor absorbed dose; (4) (188)ReO(4), a potent beta(-) emitter, is more efficient than (131)I to enhance the survival of rats bearing F98/hNIS gliomas. These studies demonstrate the importance of radiopharmaceutical selection, dose, and timing of treatment to optimize the therapeutic effectiveness of NIS-targeted radionuclide therapy following gene transfer into gliomas.

In the present study, whole-cell patch-clamp recording was used to study whether vascular endothelial growth factor (VEGF) had a regulatory effect on the potassium-channel currents. The outward delayed-rectifier potassium currents (I(K)) were recorded in acutely isolated hippocampal neurons from 14-day-old rat brains. A local application of VEGF at the concentrations from 50 ng/ml to 200 ng/ml dose-dependently inhibited I(K). Administration of VEGF (100 ng/ml) to the neurons only for seconds could significantly reduce I(K) in 26 of 39 recorded cells. The currents could recover to 82.8+/-3.7% of the control level at 60 s after removing VEGF in the buffer. In the I-V curve analysis, VEGF negatively shifted the I-V curve of I(K); the inhibition was gradually enhanced as the membrane potential increased from -40 mV to 50 mV in 13 cells. Thus, the results reveal that VEGF inhibits I(K) in acute, reversible and voltage-dependent manners. Double staining combined with confocal laser scanning microscopy was used to simultaneously detect the distribution of VEGF receptors (flt-1 and flk-1) in the hippocampal section and isolated neuron. Results showed that flt-1-positive staining, but not flk-1, could be observed on the membrane of the hippocampal neuron in both preparations, suggesting the presence of neuronal membrane VEGF flt-1 receptors in the hippocampus. To investigate if the inhibition by VEGF on I(K) is related to the presence of flt-1 receptors, we further did flt-1-receptor immunostaining for the recorded neurons, which was labeled with Lucifer Yellow during the recording. Among nine recorded cells, five showing the inhibition by VEGF had detectable signals for flt-1 receptors on their membrane, whereas the other four showing no inhibition had no flt-1 receptors either. The results suggest that VEGF can acutely inhibit I(K) in the hippocampal neurons probably related to the presence of membrane flt-1 receptors in the neurons.

Radioactive iodide uptake (RAIU) in thyroid follicular epithelial cells, mediated by the sodium iodide symporter (NIS), is the first rate-limiting step in iodide accumulation which provides a mechanism for effective radioiodide treatment for patients with thyroid cancer. We hypothesize that NIS gene transfer to non-thyroid tumor cells will enhance intracellular radioiodide accumulation and result in better tumor control. Here, we performed non-invasive tumor imaging and (131)I therapy studies using rats bearing intracerebral F98 gliomas that have been retrovirally transduced with human NIS. Our results show that: (1) NIS is expressed in the intracerebral F98/NIS gliomas; (2) F98/NIS gliomas can be imaged by (99m)TcO(4) (whose uptake is also mediated by NIS) and (123)I scintigraphy; (3) significant amounts of radioiodide were retained in the tumors at 24 h after (123)I injection; (4) RAIU and NIS expression in the thyroid gland can be reduced by feeding a thyroxine-supplemented diet; and (5) survival time was increased in rats bearing F98/hNIS tumors by (131)I treatment. These studies warrant further investigating tumor imaging and therapeutic strategies based on NIS gene transfer followed by radioiodide administration in a variety of human cancers.

Previous mutational analysis for BRCA gene mutations in sporadic ovarian cancer occurring in Chinese patients in Hong Kong identified six germline BRCA1 mutations and one germline BRCA2 mutation, six of which were novel (Khoo et al., 2000). Knowledge of BRCA gene mutations in the Chinese population is relatively scant. In this study, we focussed on whether any of these mutations could be recurrent in our Chinese population, making use of archival paraffin embedded tissue. A consecutive series of 214 ovarian cancer cases, half of Southern Chinese origin from Hong Kong whilst the other half of Northern Chinese origin from Beijing were used for the study. We identified one further novel mutation, 1081delG, in BRCA1. This was found to occur in two unrelated individuals with shared haplotype as revealed by allelotype analysis, thus demonstrating founder effect. Two other recurrent mutations were also identified, the 2371-2372delTG mutation in BRCA1 and the 3337C>T mutation in BRCA2 recurring in two and three unrelated individuals respectively, giving an overall prevalence 4.7% of recurrent BRCA mutations in ovarian cancer in the Southern Chinese population. Most importantly, all our recurrent mutation carriers were identified from Southern Chinese patients from Hong Kong whilst such mutations were absent in samples from the Northern Chinese. Our findings indicate possible heterogeneity in the BRCA genotype between Northern and Southern Chinese. The identification of a founder mutation and two recurrent mutations moreover, has important implications towards screening strategies for breast and ovarian cancer among Chinese of southern ancestral origin who are now dispersed throughout the world., (Copyright 2002 Wiley-Liss, Inc.)

Radioiodine-concentrating activity in thyroid tissues has allowed the use of radioiodine as a diagnostic and therapeutic agent for patients with thyroid disorders such as well-differentiated thyroid cancer. However, some extrathyroidal tissues also take up radioiodine, contributing to unwanted side effects of radioiodine therapy. Now that the molecule that mediates radioiodine uptake, the sodium iodide symporter (NIS), has been cloned and characterized, it may be possible to develop novel strategies to differentially modulate NIS expression and/or activity, enhancing it in target tissues and impeding it in others. In addition to restoring NIS expression/activity to ensure sufficient radioiodine uptake for the diagnosis and treatment of advanced thyroid cancers, we envision that it may be possible to selectively increase or confer NIS expression/activity in tumors of nonthyroidal tissues to facilitate the use of radioiodine in their diagnosis and treatment. We also consider the molecular basis of thyroid and nonthyroid disorders that may be complicated by NIS deregulation. Finally, we explore the use of NIS as an imaging reporter gene to monitor the expression profile of the transgene in transgenic mouse animal models and in patients undergoing gene therapy clinical trials.

Background: Primary peritoneal malignant mixed Müllerian tumors (MMMTs) are rarely reported in the literature., Methods: The clinical, pathologic, and immunohistochemical features of five cases of MMMT of female peritoneum were analyzed. The tumors were also investigated for expression of hormone receptors, specific BRCA-1 mutations, and clonality., Results: The patients' ages ranged from 33 to 67 years. They presented with abdominal pain or mass. One case of peritoneal MMMT was associated with a synchronous endometrial carcinoma whereas another case was detected 2 years after the diagnosis of a primary adenocarcinoma of the fallopian tube. One patient died 1 month after diagnosis whereas 2 patients died with disease within 1 year. Both carcinomatous and sarcomatous elements are present in all the tumors. Squamous differentiation was noted in two cases. Heterologous elements, including chondroid, rhabodomyoblastic, and osteoid differentiation were detected in all tumors. Immunohistochemical studies confirm the biphasic differentiation with variable demonstration of neural and smooth muscle differentiation. All five MMMTs were negative for estrogen and progestogen receptors although the related endometrial and tubal carcinomas were positive. Heteroduplex analysis used to screen for specific BRCA-1 mutations were negative in all five MMMTs. Clonality study of the two MMMTs found in association with endometrial carcinoma and tubal carcinoma was inconclusive., Conclusions: Our study confirmed that primary peritoneal MMMTs were aggressive tumors with poor prognosis. The presence of synchronous or metachronous genital carcinomas suggests multifocal tumorigenesis from tissue of same embryologic origin. The lack of hormone receptor in these tumors indicates deviation from hormonal control. Specific BRCA-1 mutations found in ovarian carcinoma in Chinese patients could not be detected in our series., (Copyright 2001 American Cancer Society.)

Aims: To investigate the pattern of telomerase activity in hydatidiform mole as compared with normal placenta and choriocarcinoma, and to determine the prognostic significance of telomerase activity in hydatidiform mole., Methods: Telomerase activity in 35 cases of hydatidiform mole, 35 normal placentas, one choriocarcinoma sample, and two choriocarcinoma cell lines (JAR, JEG3) was determined using the sensitive polymerase chain reaction based telomeric repeat amplification protocol (TRAP) assay. Two cases of breast carcinoma and two cases of ovarian carcinoma were also included as positive controls in the telomerase assay., Results: Telomerase activity was detected in 11 of 30 early placentas (36.7%), one of five term placentas (20%), five of 27 hydatidiform moles which regressed spontaneously (18.5%), and six of eight hydatidiform moles which developed persistent trophoblastic disease (75%) (including three which developed metastases). Hydatidiform moles which subsequently developed persistent disease, especially those which metastasised, were more likely to express telomerase activity (p < 0.01). However, there was no significant difference in the frequency of telomerase activity between early placentas and hydatidiform mole. Strong telomerase activity was observed in choriocarcinoma tissue, choriocarcinoma cell lines, and ovarian and breast carcinomas., Conclusions: Telomerase activation occurs in hydatidiform mole with a similar incidence to early normal placentas. This supports the concept that hydatidiform mole is essentially an abnormal conceptus. There is an association between telomerase activation and the development of persistent trophoblastic disease. Further study is warrant to confirm the prognostic significance of telomerase activity in hydatidiform mole.

The role of p53 in the pathogenesis of gestational trophoblastic disease (GTD) was investigated. Immunohistochemical studies for p53, its regulator mdm2, and proliferation marker Ki67 were performed on paraffin-embedded tissues of 28 partial moles (PM), 57 complete moles (CM), 14 choriocarcinomas (CCA), and 31 normal placentas. Three antibodies to p53 (DO-7, Ab-2, Ab-3) were used and demonstrated immunoreactivity for wild-type p53 protein predominantly in the nuclei of cytotrophoblasts. Direct DNA sequencing of 36 hydatidiform moles using frozen tissues confirmed an absence of mutational changes in exons 5-8. CCA was found to have the highest p53 protein expression, followed by CM, PM, and normal placenta (P < 0.001). In normal placentas (P = 0.0001), PM, and CM (P = 0.016), an inverse correlation between their gestational age and p53 expression was observed. p53 expression was found to correlate with proliferation index in normal placenta (P = 0.0001) and all three groups of GTD (P = 0.012). Significant correlation between p53 and mdm2 expression was also observed (P < 0.01). The distinctive expression of p53 wild-type protein in the cytotrophoblasts and its positive correlation with the proliferative index suggests that its overexpression in GTD may be related to its effect on cell proliferation. The parallel expression of mdm2 and p53 also supports the presence of an autoregulatory feedback loop in the control of this process. No correlation could be found between clinical progress of the patients with hydatidiform moles, and the p53 (P = 0.78) or mdm2 protein (P = 0.54) expression suggesting that neither of them carries any prognostic significance.

The chromosomal composition of cancers arising in ovarian mature cystic teratoma (MCT) was analyzed using chromosome in situ hybridization (CISH) performed on paraffin-embedded material from 10 squamous cell carcinomas, 1 adenocarcinoma, 1 thyroid papillary carcinoma, and 1 strumal carcinoid. Cervical tissue from seven of these patients was used as a control. In the cancers, a relative gain of chromosome 16 (in 7 cases), chromosome 12 (in 9), chromosome 11 (in 10), and chromosome X (in 8) was detected. Trisomy 12 was diagnosed in eight cases. No chromosomal aberrations were detected in the strumal carcinoid. In the benign areas of the MCTs, only one case showed a gain of chromosome 11, although, in another case, there was a gain of chromosome X. Malignant transformation of MCTs often occurs in association with complex chromosome aberrations that may play a role in the development of such carcinomas.

Recent studies in Western populations have shown that trisomy 3 is the most frequent chromosomal abnormality in primary gastric lymphoma (PGL). To study the incidence of trisomy 3 and its implications for the pathogenesis of PGL in Hong Kong, we have applied the technique of chromosome in situ hybridization in 13 cases of PGL by using archival paraffin-embedded tissue sections. Five cases of chronic gastritis were used as controls. Trisomy 3 was found in 9 (69%) of 13 cases, including cases of low-grade lymphoma and high-grade lymphoma with or without a low-grade component. Our findings are similar to the incidence of trisomy 3 reported in the Western literature. The persistent finding of trisomy 3 in various histologic grades of PGL suggests that it may be useful as a clonal marker in this group of neoplasms. Various molecular events involving chromosome 3 may be related to the pathogenesis of this group of lymphomas.

Objective: To evaluate the origin of pseudomyxoma peritonei (PMP) in Chinese women., Methods: The clinicopathologic features of 15 cases of PMP were reviewed. Immunostaining using antibodies for CK7 and CK20 was performed in the ovarian, appendiceal and peritoneal lesions of these cases., Results: Appendiceal pathology was documented in five cases, including four mucinous cystadenoma and one simple mucocele. Eight ovarian tumors were found, including seven mucinous cystadenocarcinomas of low malignant potential and one mucinous cystadenoma. Synchronous ovarian and appendiceal lesions were discovered in three cases. One patient had adenocarcinoma of the pancreas. The origin of mucin production was not known in four cases with metastatic adenocarcinoma found in two of them. Immunoreactivity for CK20 was demonstrated in the tissues derived from the peritoneum, ovary, appendix and pancreas while only 23% (3 out of 13 women) of the peritoneal lesions and 33% (2 out of 6 women) of the ovarian tumors were immunoreactive for CK7., Conclusions: PMP is a heterogeneous lesion, which may develop from mucinous metaplasia of the peritoneum or from appendiceal, or ovarian lesions. Careful examination of the ovary and appendix with performance of appendectomy is advised in every case of PMP. Immunohistochemical examination of the peritoneal, ovarian or appendiceal lesions using antibodies, in particular that for CK7 would help in defining the origin of mucin production.

Background: The p21WAF1/CIP1 gene mediates growth arrest by inhibiting G1 cyclin dependent kinases and has been considered as a downstream effector of the tumour suppressor gene p53., Aim: To analyse the role of p21WAF1/CIP1 in gestational trophoblastic disease., Methods: The immunohistochemical expression of p21WAF1/CIP1 gene was measured in 33 placentas, 28 partial hydatidiform moles, 54 complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1) immunoreactivity as well as clinical progress., Results: p21WAF1/CIP1 immunoreactivity was found predominantly in the nuclei of the syncytiotrophoblasts. p21WAF1/CIP1 protein expression correlated with gestational age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89). Complete hydatidiform moles and choriocarcinomas had a significantly higher p21WAF1/CIP1 expression compared with normal placentas and partial hydatidiform moles (p < 0.001); there was no difference between placentas and partial hydatidiform moles. No correlation between p21WAF1/CIP1 expression and either the proliferation (Ki67) index (p = 0.34) or p53 protein accumulation (p = 0.68) was demonstrated. There was no significant difference (p > 0.05) in p21WAF1/CIP1 expression between the 17 patients who developed persistent gestational trophoblastic disease and those who did not., Conclusions: This study suggests that p21WAF1/CIP1 expression in trophoblastic disease may be induced by a p53 independent pathway. The proliferative activity of gestational trophoblastic diseases might not be determined solely by the control of the cell cycle operated by p21WAF1/CIP1. p21WAF1/CIP1 expression is not an accurate prognostic indicator of gestational trophoblastic disease.