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Background Epithelial ovarian cancer development before menarche is extremely rare. Case We report a prepubertal girl who developed ovarian mucinous carcinoma with mural carcinosarcomatous components. Summary and Conclusion Magnetic resonance imaging showed a polycystic mass with solid components. The left adnexa was removed. Histological analysis revealed a mucinous tumor with mural carcinosarcomatous components. Three weeks later, ascites and peritoneal metastasis were detected. The patient received a combination therapy of paclitaxel with carboplatin. After 4 chemotherapy cycles the right adnexa, uterus, partial omentum, and pelvic peritoneum were removed. Four additional paclitaxel/carboplatin therapy cycles were administered. She remains free from recurrence after 29 months. To our knowledge, this is the first report of ovarian mucinous carcinoma with mural carcinosarcomatous components in a prepubertal girl.

AimThe aim of this study was to evaluate the impact of surgical staging in stage I clear cell adenocarcinoma of the ovary (CCC).MethodsWe performed a retrospective review of 165 patients with stage I CCC treated with optimal or nonoptimal staging surgery.ResultsThe median follow-up period in this study was 67 months. No significant difference was detected in recurrence-free survival (RFS) or overall survival (OS) between patients optimally and nonoptimally staged (RFS: P = 0.434; OS: P = 0.759). The estimated 5-year RFS and OS rates were 92.1% and 95.3% in patients with stages IA/IC1 and 81.0% and 83.7% in stages IC2/IC3, respectively. The multivariate analysis indicated that stages IC2/IC3 predicted worse RFS and OS than stages IA/IC1 in stage I CCC patients (RFS: P = 0.011; OS: P = 0.011). Subsequently, we investigated the impact of surgical staging, respectively, in stages IA/IC1 and stages IC2/IC3. Significant differences were observed in PFS and OS between patients optimally and nonoptimally staged with stages IA/IC1 (RFS: P = 0.021; OS: P = 0.024), but no significant difference was found in those with stages IC2/IC3. The multivariate analysis indicated that nonoptimal staging surgery predicted worse RFS than the optimal staging surgery in stages IA/IC1 CCC patients (P = 0.033). In addition, we investigated the impact of surgical staging for stages IA/IC1 in the adjuvant chemotherapy group. The 5-year RFS and OS rates in patients optimally and nonoptimally staged with stages IA/IC1 in the adjuvant chemotherapy group were 97.8% and 100%, and 85.2% and 89.4%, respectively. The multivariate analysis indicated that nonoptimal staging surgery predicted worse RFS than the optimal staging surgery for stages IA/IC1 patients in the adjuvant chemotherapy group (P = 0.019).ConclusionsThe prognosis for women with stage 1A/IC1 is very good. Surgical staging category was the only independent prognostic factor for RFS in stages IA/IC1 CCC.

Background Dose-dense weekly paclitaxel (Taxol) and carboplatin (dd-TC) improved survival compared with conventional tri-weekly paclitaxel and carboplatin (c-TC) as a first-line chemotherapy for newly diagnosed stage II–IV ovarian cancer in the Japanese Gynecologic Oncology Group 3016 trial. We report the quality-of-life (QoL) results from this trial. Patients and methods A total of 637 patients were randomly assigned to receive c-TC or dd-TC (c-TC, n = 319; dd-TC, n = 312) and were asked to complete a QoL assessment at baseline, just after the third and sixth chemotherapy cycles, and at 12 months after randomization. QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-general (FACT-G), FACT-taxane subscale (FACT-T), and FACT-ovary subscale (FACT-Ov). The overall QoL and that according to each subscale were analyzed using mixed-effects models adjusted for treatment and time. Results Baseline QoL assessment was completed by 204 out of 319 (63.9%) and 200 out of 312 (64.1%) patients in the c-TC and dd-TC groups, respectively. In these groups, the compliance rates with regard to QoL assessment were 74.5% and 73.0%, respectively, after three chemotherapy cycles; 86.8% and 86.9%, respectively, after six chemotherapy cycles; and 74.2% and 71.6%, respectively, at 12 months after randomization. The overall QoL did not differ significantly between the two treatment groups up to 12 months after randomization (P = 0.46). However, QoL according to the FACT-T subscale was significantly lower in the dd-TC group than in the c-TC group (P = 0.02). Conclusion dd-TC does not decrease overall QoL compared with c-TC. Clinical trial information NCT00226915.

Previous studies have identified microRNA (miRNA) involvement in human cancers. This study aimed to elucidate potential clinical and biological associations of ovarian cancer-related miRNA gene expression profiles in high-grade serous carcinoma (HGSC) and ovarian clear cell carcinoma (OCCC). Accordingly, we investigated 27 patients with ovarian cancer (12 HGSC and 15 OCCC cases) using quantitative real-time reverse transcription polymerase chain reaction to determine the cancer-related miRNA expressions. Gene Cluster 3.0 was used for hierarchical clustering analysis, and differentially expressed miRNAs between HGSC and OCCC were identified by the class comparison analysis using BRB-ArrayTools. An unsupervised hierarchical clustering analysis identified two distinct miRNA expression clusters, with histological subtype-related significant differences in the associations between clusters and clinicopathological features. A comparison of miRNA expression in HGSCs and OCCCs identified five miRNAs (miR-132, miR-9, miR-126, miR-34a, and miR-21), with OCCCs demonstrating a statistically higher expression. Further investigation of the biological significance of miR-9 overexpression in OCCC revealed that miR-9 inhibition reduced the cell invasion ability and upregulated E-cadherin expression. Using a luciferase reporter assay, we further demonstrated the direct binding of miR-9 to E-cadherin. Global cancer-related miRNA expression analysis identified statistically unique profiles that could discriminate ovarian cancer histotypes. In OCCC, miR-9 overexpression may affect pathogenesis by targeting E-cadherin, thereby inducing an epithelial–mesenchymal transition. Therefore, miR-9 may be a promising therapeutic target strategy for OCCC.

Objective Patients with adeno/adenosquamous carcinoma may have a poorer prognosis than patients with squamous cell carcinoma. Radiotherapy and concurrent chemoradiotherapy are used as adjuvant therapies for cervical cancer, regardless of the histological subtype. The aim of this study was to investigate the prognostic outcome of adjuvant therapy for patients with adeno/adenosquamous carcinoma with pathological risk factors. Methods The medical records of 135 patients with stage IB-IIB cervical cancer with squamous cell carcinoma or adeno/adenosquamous carcinoma who underwent primary surgery followed by adjuvant therapy were retrospectively reviewed. Patients with a pathologically confirmed bulky tumor (≥4 cm), nodal metastasis and/or parametrium invasion were included in the study. Results The median follow-up period was 48 (1-132) months. Of the 135 patients, 90 with squamous cell carcinoma and 23 with adeno/adenosquamous carcinoma were treated with adjuvant radiotherapy and concurrent chemoradiotherapy (SCC-RT/CCRT and AC-RT/CCRT groups), and 22 with adeno/adenosquamous carcinoma were treated with adjuvant systemic chemotherapy (AC-CT group). There were no significant differences in clinicopathological factors between the SCC-RT/CCRT and AC-RT/CCRT groups and between the AC-RT/CCRT and AC-CT groups. Progression-free survival was significantly shorter in the AC-RT/CCRT group compared to the SCC-RT/CCRT group (P = 0.002). Adeno/adenosquamous carcinoma histology and multiple lymph node metastasis were independent prognostic factors for shorter progression-free survival in patients treated with adjuvant radiotherapy and concurrent chemoradiotherapy. Progression-free survival was also significantly shorter in the AC-RT/CCRT group compared to the AC-CT group (P = 0.026). Conclusions Adjuvant radiotherapy and concurrent chemoradiotherapy may be less effective for patients with adeno/adenosquamous carcinoma than for those with squamous cell carcinoma. Adjuvant systemic chemotherapy may be beneficial for adeno/adenosquamous carcinoma and further studies are warranted.

When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC) include 1) a higher incidence among Japanese, 2) an association with endometriosis, 3) poor prognosis in advanced stages, and 4) a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH) to identify somatic copy number alterations (SCNAs) associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC. The entire 8q chromosome (minimum corrected p-value: q = 0.0001) and chromosome 20q13.2 including the ZNF217 locus (q = 0.0078) were amplified significantly more in Japanese than in Korean or German samples. This copy number amplification of the ZNF217 gene was confirmed by quantitative real-time polymerase chain reaction (Q-PCR). ZNF217 RNA levels were also higher in Japanese tumor samples than in non-Japanese samples (P = 0.027). Moreover, endometriosis was associated with amplification of EGFR gene (q = 0.047), which was again confirmed by Q-PCR and correlated with EGFR RNA expression. However, no SCNAs were significantly associated with prognosis or thrombosis. These results indicated that there may be an association between CCC and ZNF217 amplification among Japanese patients as well as between endometriosis and EGFR gene amplifications.

Among epithelial ovarian cancers, clear cell carcinoma of the ovary (CCC) has unique clinical and molecular characteristics that include chemoresistance resulting in poor prognosis. It was shown that CCC recently was characterized by specific upregulation of the IL-6/IL-6R-signal transducer and activator of transcription 3 (Stat3) signaling pathway. In this study, we aim to clarify whether IL-6/IL-6R mediated signaling pathway could have clinical relations with CCC and to evaluate inhibitory effects of the pathway on CCC carcinogenesis. A total of 84 CCC cases collected from primary surgical specimens were evaluated by the immunohistochemical analysis for IL-6R and phosphorylated Stat3 (pStat3), and we found that high IL-6R expression correlated with poor patient survival both by the univariate and multivariate analyses, suggesting that IL-6/IL-6R signaling pathway could be implicated in the progression of CCC. We further investigated the effects of IL-6/IL-6R mediated signaling pathway inhibition either by IL-6R small interfering RNA (siRNA) approach or humanized anti-human IL-6R antibody (tocilizumab) in CCC. Inhibition of endogenous IL-6R including tocilizumab in CCC cells did reduce cell invasion ability and restored their response to cytotoxic reagent. These data suggest that IL-6/IL-6R signaling pathway could act on CCC cells to enhance invasion and chemoresistance and, therefore, targeting IL-6/IL-6R mediated signaling pathway could be a promising therapeutic strategy for CCC.

In advanced epithelial ovarian and peritoneal cancer, residual tumor diameter correlates with prognosis; therefore, maximum debulking and optimal surgery (OS) for residual tumors

Recently, we found nonsense and missense mutations of the PPP1R3 (protein phosphatase 1, regulatory subunit 3) gene in diverse human cancer cell lines and primary lung carcinomas, indicating that PPP1R3 functions as a tumor suppressor in human carcinogenesis. In this study, to assess the prevalence of PPP1R3 mutations in human primary cancers and the genetic diversity of the PPP1R3 gene in the human population, somatic mutations and genetic polymorphisms in the PPP1R3 gene were examined in 137 pairs of cancerous and non-cancerous tissues of patients with cancers of colon, ovary, and liver. Five somatic mutations including two missense mutations were detected in three cancerous tissues consisting of two colorectal carcinomas and one ovarian carcinoma. Five novel single nucleotide polymorphisms (SNPs) associated with the substitution of amino acids were also identified in cancer patients, in addition to five known nonsynonymous SNPs, including three previously reported ones as having an impact on the susceptibility to insulin resistant disorders. Differences in the activities and properties of multiple PPP1R3 proteins, which are produced in human cells due to variable somatic mutations and genetic polymorphisms in the PPP1R3 gene, can be involved in human carcinogenesis and susceptibility to diseases.

Several previous reports showed that irinotecan hydrochloride plus cisplatin (CPT-P) was a candidate first-line chemotherapy regimen for clear cell adenocarcinoma of the ovary (CCC). However, long-term survival in CCC patients treated with CPT-P as first-line chemotherapy remains to be determined. The aim of the present study was to evaluate the long-term results of CPT-P as first-line chemotherapy for CCC.We performed a retrospective review of 31 patients with CCC who were treated with CPT-P between 1996 and 2004.The median follow-up period was 91 months. The estimated 8-year overall survival (OS) rate in all patients was 64.5%, while the rate in 18 stage I, 21 stage I/II, and 10 stage III/IV patients was 88.9%, 85.7%, and 20.0%, respectively. The estimated 8-year OS rate in patients with pT1/pT2 disease was 87.0%, while the 3-year OS rate in patients with pT3 disease was 0%. Univariate analysis using the log-rank test revealed that Eastern Cooperative Oncology Group performance-status 1, pT3 stage, and presence of residual disease (stage II-IV) were significantly correlated with shortened patient survival. Multiple regression analysis revealed that pT3 predicted worse OS in patients with CCC than pT1 (P0.001) or pT2 disease (P 0.005).The long-term results suggest CPT-P as a candidate in first-line chemotherapy for CCC in not only stage I, but also in optimally debulked stage II-IV patients with pT1/pT2 disease.

CD147 is a membrane glycoprotein that is expressed in various cancer cells and is involved in tumor invasion and metastasis by inducing stromal fibroblastic cells to produce matrix metalloproteinases. This study was carried out to evaluate the correlation between CD147 expression and various clinicopathologic parameters, including histological grade and prognosis in a small sample set of human ovarian cancer patients.Paraffin-embedded surgical tissue samples from 25 patients with ovarian serous and endometrioid adenocarcinoma were stained with anti-CD147 antibody (monoclonal antibody 12C3: MoAb 12C3) for immunohistochemical analysis.CD147 protein was expressed in 84.0% (21 of 25 cases) of cancerous lesions, but not in normal lesions. CD147 expression by ovarian cancer cells was inversely correlated with overall survival. There was no correlation between CD147 expression and histological grade.These results suggest that measurement of CD147 expression may enhance the understanding of the pathophysiology of epithelial ovarian cancer.

Ovarian clear cell carcinoma (OCCC) has several significant characteristics based on molecular features that are distinct from those of ovarian high-grade serous carcinoma. Cellular glycogen accumulation is the most conspicuous feature of OCCC and in the present study its metabolic mechanism was investigated. The amount of glycogen in cells cultured under hypoxia increased significantly and approximately doubled after 48 h (P

Cytokine expression in a tumor microenvironment can impact both host defense against the tumor and tumor cell survival. In this study, we sought to clarify whether the cytokine gene expression profile could have clinical associations with ovarian cancer. We analyzed the expression of 16 cytokine genes (IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-γ, TNF-α, IL-6, HLA-DRA, HLA-DPA1 and CSF1) in 50 ovarian carcinomas. Hierarchical clustering analysis of these tumors was carried out using Cluster software and differentially expressed genes were examined between clear cell carcinoma (CCC) and other subtypes. Following this examination we evaluated the biological significance of IL-6 knockdown in CCC. Unsupervised hierarchical clustering analysis of cytokine gene expression revealed two distinct clusters. The relationship between the two clusters and clinical parameters showed statistically significant differences in CCC compared to other histologies. CCC showed a dominant Th-2 cytokine expression pattern driven largely by IL-6 expression. Inhibition of IL-6 in CCC cells suppressed Stat3 signaling and rendered cells sensitive to cytotoxic agents. The unique cytokine expression pattern found in CCC may be involved in the pathogenesis of this subtype. In particular, high IL-6 expression appears likely to be driven by the tumor cells, fueling an autocrine pathway involving IL-6 expression and Stat3 activation and may influence survival when exposed to cytotoxic chemotherapy. Modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for CCC.

Introduction: Paclitaxel plus carboplatin (TC) is generally considered to be the "gold standard" regimen for treatment of epithelial ovarian carcinomas. Little data are available, however, on the use of this regimen in patients with clear cell adenocarcinoma of the ovary (CCC). Combination chemotherapy with irinotecan hydrochloride plus cisplatin has been reported to be effective for primary and recurrent or resistant CCC. We compared these 2 combinations in patients with CCC. Methods: Patients (n = 99) with CCC were randomly assigned to receive either 180 mg/m2 paclitaxel on day 1 plus AUC 6 mg/mL × minute carboplatin on day 1 every 21 days (TC arm) or 60 mg/m2 irinotecan hydrochloride on days 1, 8, 15 plus 60 mg/m2 cisplatin on day 1 every 28 days (CPT-P arm). Results: Percentages of patients receiving the scheduled 6 cycles of chemotherapy in the TC and CPT-P arms were 70.8% and 72.0%, respectively. Although toxicity was well tolerated in both arms, the toxicity profile of each arm differed. Progression-free survival (PFS) showed no significant difference between the 2 treatment groups. Because there were more patients with large residual disease in the CPT-P arm, we performed a subset analysis by removing those patients, and then compared the PFS with that of patients without residual disease or with residual disease less than 2 cm. The PFS tended to be longer in the CPT-P group, although the difference was not statistically significant. Conclusions: A phase III randomized trial is required to elucidate the effectiveness of CPT-P combination chemotherapy for CCC.

Most ovarian cancers arise from the mesothelial surface lining of the ovaries or from invaginations of this lining into the superficial ovarian cortex that form cortical inclusion cysts. Thus, these cysts are thought to be precursor lesions of ovarian carcinoma. Epithelial-mesenchymal transition, which is a transcriptional program for inducing maintenance of the mesenchymal phenotype, acts in tumor progression and metastasis. Little is known about the mechanisms involved in mesenchymal-epithelial transition (MET). We aimed to characterize the human ovarian surface epithelium (OSE) and inclusion cysts by immunohistochemical analysis to examine whether MET occurs during inclusion cyst formation in the OSE. We used specimens from 9 endometrial cancer patients who had undergone hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemical analysis was performed in 10 normal ovaries containing 92 inclusion cysts and in 4 normal tubes to examine the expression of antigen markers including calretinin, podoplanin, D2-40, thrombomodulin, HBME-1, vimentin, EMA, WT1, CA125, MOC31, TAG-72, Ber-EP4 and E-cadherin. The positive staining rates for mesothelial markers in normal OSE were 100% (10/10) for calretinin, 80% (8/10) for podoplanin, 80% (8/10) for D2-40, 70% (7/10) for thrombomodulin, 100% (10/10) for HBME-1, 100% (10/10) for vimentin. The positive staining rates for epithelial markers in tubal epithelium were 100% (4/4) for HBME-1, 100% (4/4) for vimentin, 100% (4/4) for EMA, 75% (3/4) for TAG-72, 100% (4/4) for Ber-EP4. Inclusion cysts showed positive staining for both markers with an incidence of 51% (47/92) for HBME-1, 44% (41/92) for vimentin, 65% (60/92) for TAG-72, 88% (81/92) for Ber-EP4. The OSE showed the characteristics of both mesenchymal and epithelium cells. In contrast, inclusion cysts gained epithelial characteristics, but lost mesenchymal characteristics. These findings support that MET occurs during the inclusion cyst formation from OSE.

Patients with ovarian clear cell adenocarcinoma (OCCA) show a poor response to conventional platinum-based chemotherapy. Recently, it was reported that combination chemotherapy with cisplatin plus irinotecan hydrochloride (P-CPT) achieves high response rates for primary advanced and recurrent or resistant OCCA. We retrospectively reviewed the outcome of 20 OCCA patients treated with P-CPT by the Gynecology Service at The Jikei University Hospital after initial surgery. These patients received a total of 101 cycles of P-CPT, with a median of 5 cycles each. Two complete responses (CRs) were obtained in the three patients with measurable disease, and response duration was 7 and 15 months, respectively. One patient had stable disease (SD), and the time to progression was 5 months. The estimated 3- and 5-year survival rates were 69% and 69%, respectively. Our current data and previous reports suggest that P-CPT is a candidate first-line chemotherapy regimen for OCCA.

We previously reported that indoleamine-2,3-dioxygenase (IDO) is associated with paclitaxel resistance and that IDO serves as a marker of poor prognosis in ovarian serous adenocarcinomas (SA). In this study, to explore the role of IDO in the development of various histological types of ovarian cancer, we further examined IDO expression not only in SA but also in other types of ovarian cancers. Expression of IDO protein was analyzed by immunohistochemistry for a total of 122 ovarian cancers including 40 SA, 67 clear cell adenocarcinomas (CCA), and 15 endometrioid adenocarcinomas (EA) with informed consent. Among these cases, there were 11 CCA accompanied with endometriosis and 60 cases with lymph node metastasis. We classified the samples into four categories by IDO staining pattern. IDO staining was positive in 57.5% of SA, 49.2% of CCA, and 73.3% of EA, respectively. The Kaplan-Meier survival curve showed a clear relationship between staining score and overall survival for patients with advanced (stages III and IV) SA (n=33) who underwent optimal surgery and paclitaxel-carboplatin (TC) chemotherapy as a first-line regimen. There was no association between IDO staining score and overall survival in the CCA cases. Eight of 11 cases (72.7%) of CCA accompanied by endometriosis presented identical staining patterns of IDO between CCA and endometriosis. In 43 of 60 cases (71.6%) with lymph node metastasis, the staining patterns of IDO showed a correspondence between the primary lesion and metastatic site. These results suggested that the increased synthesis of IDO protein was positively associated with impaired survival only in the serous type of ovarian cancer.

The administration of chemotherapeutic drugs during pregnancy is rare. We describe a case of malignant ovarian tumor complicating pregnancy.After laparotomy at 18 weeks of gestation, the patient received three courses of cisplatin, vinblastine, and bleomycin. Elective cesarean delivery was performed at 31 weeks of gestation. A normal infant was delivered, and no evidence of tumor recurrence was observed. Metastasis to the liver was detected in the fifth month after delivery. However, this was treated successfully with three courses of cisplatin, etoposide, and bleomycin. There was no evidence of recurrence observed at 65 months after the initial treatment.Although the risk of chemotherapy to the fetus cannot be assessed based on a single case, this experience is encouraging.

Multiagent chemotherapy for small cell carcinoma of the ovary (SCCO) may contribute to the prolonged survival of young women who are suffering from this disease, even in the advanced stage with remaining tumor, although the rarity of SCCO complicates the generalization of chemotherapy agents and operation methods for this disease. A 24-year-old patient with SCCO FIGO stage IIC is alive after recurrences and chemotherapy including cisplatin + etoposide after the first operation and docetaxel for the second recurrence. She is now doing well with no evidence of disease more than 4 years after the first operation and 2 years after docetaxel treatment. This may be the first report describing the use of docetaxel that may be included in multiagent chemotherapy.

Purpose: We aimed to find key molecules associated with chemoresistance in ovarian cancer using gene expression profiling as a screening tool. Experimental Design: Using two newly established paclitaxel-resistant ovarian cancer cell lines from an original paclitaxel-sensitive cell line and four supersensitive and four refractory surgical ovarian cancer specimens from paclitaxel-based chemotherapy, molecules associated with chemoresistance were screened with gene expression profiling arrays containing 39,000 genes. We further analyzed 44 genes that showed significantly different expressions between paclitaxel-sensitive samples and paclitaxel-resistant samples with permutation tests, which were common in cell lines and patients' tumors. Results: Eight of these genes showed reproducible results with real-time reverse transcription-PCR, of which indoleamine 2,3-dioxygenase gene expression was the most prominent and consistent. Moreover, by immunohistochemical analysis using a total of 24 serous-type ovarian cancer surgical specimens (stage III, n = 21; stage IV, n = 7), excluding samples used for GeneChip analysis, the Kaplan-Meier survival curve showed a clear relationship between indoleamine 2,3-dioxygenase staining patterns and overall survival (log-rank test, P = 0.0001). All patients classified as negative survived without relapse. The 50% survival of patients classified as sporadic, focal, and diffuse was 41, 17, and 11 months, respectively. Conclusion: The indoleamine 2,3-dioxygenase screened with the GeneChip was positively associated with paclitaxel resistance and with impaired survival in patients with serous-type ovarian cancer.

There have been many reports indicating that the down-regulation of p21 WAF1/C1P1 is related to carcinogenesis and the development of various tumors; nevertheless, its association with epithelial ovarian cancer (EOC) remains controversial. In this study, we focused on serous ovarian cancer, which is the most prevalent histological type, and performed immunohistochemical analysis to examine the expression of p21 WAF/C1P1 and p53 in 43 cases of serous-type EOC sourced from a single University Hospital: 14 stage I, 4 stage II, 21 stage III, and 4 stage IV. Positive p21 WAF1/C1P1 was found in 24 of 43 cases (56%), and positive p53 was detected in 21 of 43 cases (49%). Among stage III/IV cases, positive p21 WAF1/C1P1 staining was found in 11 of 25 cases (44%), and positive p53 staining was detected in 13 of 25 cases (52%). Univariate survival analysis for the entire cohort revealed that positive p21 WAF1/C1P1 was associated with a survival benefit. The 10-year survival rates of p21 WAF1/C1P1 -positive staining and p21 WAF1/C1P1 -negative staining were 82.4 and 39.5%, respectively, and there was a significant difference between the two groups (p

Pericentric inversion of chromosome 9 is a common chromosomal aberration that may be involved in the pathogenesis of several types of cancer. Screening for structural balanced chromosomal aberrations in 58 patients with ovarian carcinoma found a patient with inv(9)(p11;q13) who had repeated spontaneous abortions. To define the breakpoint at the 9p11 region, the human 9p11-specific CEPH-YAC library was first screened with fluorescence in situ hybridization (FISH) analysis, resulting in isolation of the YAC clones 961d9 and 954b9 spanning the breakpoint. Next, screening with FISH analysis of the cosmid library constructed from 961D9 isolated 3 cosmid clones that included the breakpoint. DNA sequence analysis showed that the cosmid clones spanned the 57.7-kb sequence, which contained the FGF7 [keratinocyte growth factor (KGF)]-like gene including exons 2 and 3. FISH analysis showed that the 57.7-kb sequence was duplicated from the 9p11 region to the 9q13 region on the aberrant chromosome 9. Southern blot analysis showed multiple FGF7-like genes in the 9p11 region which were also duplicated to the 9q13 region on the aberrant chromosome 9. Because the FGF7-like genes are located at 9p11 and 9q13, our results are consistent with the hypothesis that the FGF7-like genes at 9p11 and 9p13 initiate the pericentric inversion of chromosome 9. Analysis of surgical specimens of ovarian cancer with the reverse transcription-polymerase chain reaction and immunohistochemical staining showed overexpression of the FGF7 gene in 4 of 9 stage I or II cases and in 10 of 11 stage III or IV cases. These findings suggest that FGF7 plays a significant role in the development of ovarian cancer.

Uterine leiomyoma occurs in about 20-30% of women over the age of 30, and is the most frequent benign tumor in gynecology. Despite its benign status, leiomyoma of the uterus has been reported to involve chromosomal abnormalities on chromosome 7. To search for genes associated with the genesis and development of this disease, we examined microsatellite alterations on chromosome 7 in 41 uterine leiomyomas, and identified a commonly-deleted region. Allelic imbalance on chromosome 7 was detected with an incidence of 7% (3/41), with the D7S501 locus being the most frequently affected (13%). The commonly deleted region was between D7S2545 and D7S2420. We examined alterations in the expression of genes located within this region by RT-PCR. Only the LAMB1 (Laminin beta1) gene showed a variable expression. Of the 21 cases, 12 showed an increase, and 5 (24%) a decrease in the expression of LAMB1 in the leiomyomatous region. These results suggested that alteration of LAMB1 expression is associated with the genesis and development of uterine leiomyoma.

Few nonpuerperal uterine inversions have been reported, with only 101 cases during the period from 1940 to date. Moreover, uterine inversion resulting from endometrial cancer is an extremely rare condition, with only 7 reported cases. In this article, we present a case of a patient with uterine inversion caused by endometrial cancer that could be diagnosed and treated with surgery. We also discuss the mechanism of onset and present a review of the literature.

Fifty-eight stage III patients treated at The Jikei University Hospital were analysed retrospectively, in order to clarify the combination effect of maximal cytoreductive surgery and high dose cisplatin based chemotherapy in advanced ovarian cancer. They were divided into 4 groups by treatment they received which was as follows: Group A (n=25); total abdominal hysterectomy (TAH), bilateral salpingooophorectomy (BSO) and omentectomy (OMTX) done at primary surgery and followed by 5 courses of “low dose” CAP therapy (cyclophosphamide 200 mg/sq m, adriamycin 20 mg/sq m, cisplatin 35 mg/sq m every 4 weeks for 5 courses). Group B (n=4); TAH, BSO and OMTX carried out at primary surgery and followed by “high dose” CAP therapy (cyclophosphamide 200 mg/sq m, adriamycin 20 mg/sq m, cisplatin 70 mg/sq m, every 4 weeks for 5 courses and every 8–12 weeks for 5 courses thereafter). Group C (n=13) received TAH, BSO and OMTX at the primary operation and paraaortic and pelvic lymphadenectomy (LNX) at the second look operation (SLO) with “high dose” CAP therapy as did Group B. Group D (n=16), TAH, BSO, OMTX, LNX with maximal efforts made to reduce the size of the residual tumor to less than 2 cm at the primary surgery followed by “high dose” CAP therapy. The 3 year and 5 year survival rate of each group were as follows: Group A 15.6%, 15.6%, Group B 25.0%, 0%, Group C 81.8%, 0% and Group D 50.8%, 38.1%, respectively. Results indicate that a combination of maximal cytoreductive surgery and high dose cisplatin based chemotherapy contributes to the prognosis of advanced ovarian cancer patients.