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Human leukocyte antigen-G (HLA-G) gene polymorphisms and circulating sHLA-G have often been linked to the risk of breast cancer (BC). However, the results remain controversial. To resolve this issue, we performed a meta-analysis of HLA-G gene polymorphisms and sHLA-G levels in BC.We performed a meta-analysis on the association of HLA-G 14-bp Insertion/Deletion (Ins/Del) and HLA-G +3142 C/G polymorphisms with BC as well as the relationship between sHLA-G and the disease outcome.Pooled analysis showed a statistically significant association between the HLA-G 14-bp Ins/Del polymorphism and BC susceptibility for the overall population and for Caucasians. The Del allele and genotypes with at least one copy of the Del allele presented significant risks for BC. For HLA-G +3142 C/G polymorphism, the G allele significantly decreased the risk of BC for the overall population and for Caucasians, indicating that the G allele was a protective factor against BC and that the C allele was a significant risk factor for BC. The meta-analysis revealed a significantly increased level of sHLA-G patients with BC compared to the control group for the overall population, Caucasians and Asians.The present meta-analysis showed a major association of both HLA-G 14-bp Ins/Del and +3142 C/G polymorphisms with BC susceptibility, suggesting Del and C variants as highly significant risk factors for BC. The present study also showed significantly higher sHLA-G levels in patients with BC compared to healthy controls. Our pooled results suggested a critical role of HLA-G in BC, thereby providing evidence to use HLA-G as a biomarker and a therapeutic tool.

Introduction Desmoplastic small round cell tumor is a rare malignancy with poor prognosis, affecting young male patients. It frequently presents as a large abdominal mass with widespread peritoneal involvement at diagnosis. In late stages, metastases may be present. Aim We retrospectively reviewed patient characteristics, presenting symptoms, tumor pathology, treatment, and outcome of four patients with desmoplastic small round cell tumor at our institution. Cases presentation The first three cases reported are 32-, 17-, and 30-year-old North African males with intraabdominal desmoplastic small round cell tumor treated by surgery, chemotherapy, and radiation therapy with different follow-ups. The final case is a 16-year-old North African male with ganglionic desmoplastic small round cell tumor but no evidence of a tissue mass. He underwent two lines of chemotherapy with no response. The patient was lost after 2 years of follow-up. In all cases, desmoplastic small round cell tumor was confirmed by presence of t(11,22) (p13,q12) translocation. Conclusion Treatment of desmoplastic small round cell tumor is based on multidisciplinary therapy. Despite high-dose chemotherapy, extensive surgical resection, and radiotherapy, desmoplastic small round cell tumor remains lethal.

Background Breast cancer is the leading cause of cancer death in women, and most breast cancer related deaths are due to metastasis. Urinary bladder metastasis from breast cancer is rarely reported in the literature. Case presentation We report a case of a 77-year-old female with history of left breast cancer, who presented a thickening of the bladder wall at pelvic ultrasound. Biopsy confirmed that the origin was lobular carcinoma of breast origin. The patient received chemotherapy, but the clinical course of the patient was very aggressive and she died one year later. Conclusion Bladder metastasis from breast cancer is rare, but the literature reveals an increase in such occurrence over the last few years. Pathologic diagnosis relies on immunohistochemical studies. Chemotherapy and hormonal treatment represent the standard therapy, with radiotherapy being used only to control bladder bleeding. The prognosis is usually poor.

HLA-G is a non-classical major histocompatibility complex class Ib molecule. Its expression has been described in various cancer types, including ovarian cancer. HLA-G molecule has been implicated in immune escape and in progression of ovarian tumor cells. Our goal was to assess if total soluble (s)HLA-G molecules or HLA-G5 and sHLA-G1 isoforms could be considered as circulating ovarian tumor biomarkers, we measured the concentration of these molecules in ovarian carcinoma patients stratified according with their clinicopathological parameters. sHLA-G, sHLA-G1 and HLA-G5 concentrations were dosed in plasma samples by sandwich-ELISA. The sHLA-G dimerization was analyzed after immunoprecipitation and SDS-PAGE migration. Total sHLA-G and sHLA-G1 levels were significantly represented in plasma of ovarian carcinoma patients compared to healthy controls. sHLA-G1 isoform concentration was highly represented in ovarian carcinoma compared to HLA-G5 isoforms. Additionally, high sHLA-G molecules have been found in aged patients, as well as in patients with advanced stages, and those with metastatic lymph nodes and those with distant metastasis. Elsewhere, sHLA-G monomers were highly represented in ovarian carcinoma patients compared to controls. sHLA-G plasmatic protein was highly represented in ovarian carcinoma. In effect, HLA-G might be considered as a new checkpoint molecule that could be used to assess progression and recurrence of the disease, thus placing it as a potential biomarker for advanced and complicated ovarian carcinoma.

Patients with advanced endometrial cancer had generally a poor prognostic with a median survival often less than one year. Isolated bone metastases as the first sign of the disease of endometrial cancer was a very exceptional situation rarely described in the literature. The goal of this report is to describe the management of this rare site of metastases and to reviewed Clinic pathological features and prognosis of isolated bone metastases. We present a case of a 56-year-old woman treated for endometrial cancer with isolated ribs bone metastases. She was complaining about progressive right rib pain as a first sign of the disease of endometrial cancer. She had a biopsy of the lesion in the last right thoracic rib. This has proved a metastatic adenocarcinoma compatible with an endometrial primary cancer. An endometrial biopsy showed moderately differentiated endometrioid adenocarcinoma. Imagery did not reveal any other sites of metastatic disease. The patient underwent bilateral salpingo-oophorectomy and hysterectomy, peritoneal washing, omentectomy, bilateral pelvic and par aortic lymphadenectomy. In addition, a right thoracotomy was carried out and complete surgical excision of the rib mass was successfully performed. Adjuvant chemotherapy was administrated. The patient is clinically free of disease 10 months following diagnosis. Single-bone extrauterine metastatic site and local disease limited to the uterus had better survival outcomes than Stage IVb endometrial cancer with multiple metastatic sites. Therefore, the patient treated with surgery with a clear margin continued to behave as early-stage endometrial cancer.

OBJECTIVE: Primary carcinoma of the fallopian tubes is one of the less common gynecological cancers. It constitutes (0.14-0.18%) of gynecological malignancies. Our study aimed to review the managing process of primary carcinoma of the fallopian tubes in the mono-center institute and to identify prognostic factors impacting survival. STUDY DESIGN: A retrospective cohort study regarding patients with fallopian tube carcinoma treated between July 1991 and December 2005 was identified at the Tunisian anticancer institute “Salah Azaiez”. During this period, we have identified 17 patients. Data such as age, gravidity and parity, menopausal condition, symptoms reported by the patient on presentation, adjuvant therapy, stage of illness, surgical intervention, pathological findings, tumor recurrence, and previous surgical procedures were obtained from the patients’ reports. RESULTS: The average age at the time of diagnosis was 58 years. Fourteen of the included patients were postmenopausal. Surgery was the initial therapy for 15 patients. Optimal cytoreductive surgery was achievable in seven patients with no residual tumors. Histologic examination revealed that serous adenocarcinoma type was the predominant type. Two were in stage I and, four were in stage II; seven were in stage III and four in stage IV. The median follow-up time was 24 months. At the time of the final analysis, 11 patients died of disease. 5-year OS, DFS was 21% and 37% respectively. In our study, only the residual tumor was a significant prognostic factor predicting survival. CONCLUSION: Complete optimal surgery with no residual tumor was the main goal of the surgeon to improved survival in primary fallopian tube carcinoma.

HLA-G has been widely implicated in advanced cancers through different pathways of immunosuppression allowing tumor escape. Contrarily, HLA-E has a controversial role in the tumor escape from the immune system. IDO catabolic enzyme is known to be up-regulated in many tumors types allowing their immune escape. Based on these considerations, we investigated the expression of HLA-G, HLA-E and IDO molecules in endometrial cancer (EC) and their association with prognostic clinicopathologic parameters. Their expression were checked in tumoral and adjacent endometrial tissues. Both HLA-G and IDO immunostaining were significantly increased in EC tissues compared to normal residual endometrial glands (Mann Whitney U-test, p = 0.0001 and p = 0,020 respectively). However, HLA-E was highly expressed in tumoral tissues as well as in normal residual endometrial glands (respectively, 100% and 81.8%). Increased HLA-G expression levels were observed in high histological grade (grade 3), and in the non-endometrioid type 2 EC. Unexpectedly, patients with IDO Low expression had significantly impaired overall survival compared to patients with IDO High (log-rank p = 0.021). Conversely, HLA-E low expression was associated to an improved overall survival EC (log-rank p = 0.004). We concluded that, HLA-G and IDO are highly expressed in EC compared to adjacent normal endometrial tissues, that might be interesting for the EC outcome.

Clear cell sarcoma of the esophagus is very rare. The etiology of this neoplasm remains unknown. Confirmed diagnosis requires histopathology with immunochemistry and molecular study. CCS typically shows highly aggressive behavior with a high rate of local recurrence, metastases, and death from disease.

Conflicting results on the association between HLA-G and digestive cancers were reported. We conducted a meta-analysis to further investigate the true relationship between HLA-G and digestive cancers (DC).Following PRISMA guidelines, we performed a meta-analysis including 7 case-control studies on HLA-G 14-bp Insertion/deletion (I/D) polymorphism, and 15 studies on soluble HLA-G (sHLA-G). Odds ratios (OR) and their corresponding 95% confidence intervals (CI) for genetic polymorphisms were calculated. The pooled OR was calculated under three genetic models: allelic, recessive, and dominant models. Concerning sHLA-G meta-analysis, standardized mean differences (SMDs) were calculated.The HLA-G 14-bp I/D was not associated with the risk of DC. However, in the subset of HBV/HCV positive hepato-cellular cancer (HCC) patients, we reported a significant association of HLA-G 14-bp I/D with the disease initiation under allelic (D vs. I; OR = 1.698, 95% CI = 1.263-2.282, p = 0.000), dominant (DD + ID vs. II; OR = 2.321, 95% CI = 1.277-4.218, p = 0.006)and recessive (DD vs. DI + II; OR = 1.739, 95% CI = 1.173-2.577, p = 0.006) genetic models. Interestingly, HLA-G 14-bp I/D was not associated with the disease initiation in HBV/HCV negative HCC patients. However, the infection by HBV/HCV seems to be implicated in the HCC development when we compared HBV/HCV positive patients to HBV/HCV negative patients under allelic (DThe current meta-analysis supports the significant role of HLA-G in DC. The HLA-G 14-bp I/D polymorphism was associated with HCC patients with concomitant HBV/HCV viral infections. Increased sHLA-G indicated a poor prognosis for DC cancer patients.

Objectives It is widely accepted that HLA-G belongs to the group of checkpoint molecules, implicated in different pathways of immune suppression allowing tumors escape. Here, we investigated HLA-G expression in vulvar squamous cell carcinoma (VSCC) to explore the potential implication of these molecules as prognostic markers. Methods Immunohistochemistry was performed to evaluate HLA-G expression using the monoclonal antibody anti-HLA-G clone 4H84 that specifically identifies the denatured heavy chain of all HLA-G isoforms. Association with clinicopathological factors and survival were analyzed in 56 VSCC treated with radical vulvectomy. Mann-Whitney (MW) U test was used to estimate differences in HLAG levels expression in subgroups. Survival estimation was calculated by the Kaplan-Meier test. Results HLA-G was highly expressed in 11 of the 56 (19.6%) primary tumor specimens. The high HLA-G expression level was reported in high-sized tumors (PMW=0.03) and increased invasion depth (PMW=0.01). HLA-G high expression was also noted in 72,7% of advanced stages with a borderline significance (PMW=0.08). A high level of HLA-G was not associated with tumors’ resection margins (PMW=0.18). Assessment of patients’ survival by Kaplan-Meier analysis indicated an adverse correlation between HLA-Ghigh expression and overall survival rate of VSCC patients (log-rank; P=0.000037). Therefore, the 5-year cumulative survival rates of patients with HLA-Ghigh expression was 10.5%. In the same way, HLA-G high expression reduced the disease-free survival (P=0.002). Conclusions Our study shows that VSCC expresses high HLA-G that has been associated with an unfavorable clinical outcome. These findings suggest that HLA-G might be considered as a novel postoperative prognostic indicator for VSCC

Introduction/Background* Uterine leiomyosarcoma (ULS) is a rare tumor, accounting for less than 2% of uterine cancers. Its prognosis is poor because of its aggressiveness and its poor response to chemotherapy and radiation therapy. The evaluation of anatomo-pathologic conventional parameters, particularly the FIGO stage, is insufficient to predict their evolutionary profile. to better understand, the biology of these tumors is needed to assess prognosis and adapt therapeutic management. Methodology This is a retrospective study of 29 cases of ULS from the Department of Pathological Anatomy and Cytology of Salah Azaiez Institute of Tunis over 17 years (2004 -2020). The expression of estrogenic and progesterone receptors (RO and RP) was studied by immunohistochemistry (automate BOND MAX leica). Immunolabelling was assessed for the entire tumor and we established the average. The threshold of positivity chosen was 10% regardless of the intensity. Result(s)* The mean age medium was 52 years [min 39 – max 70 years]. Tumors were stage I in 48%, stage II in 14%, stage III in 24%, and stage IV in 14% of cases. We found co-expression of RO and RP in 11 cases, expression of ER only in 3 cases, expression of PR only in 4 cases, and lack of expression of both markers in 11 cases. The breakdown by FIGO stage was as follows: RO+ tumours 22%, 11%, 56% and 11%, RP+ tumours 30%, 20%, 50% and 0%. We did not find a correlation between stage and expression of RO or RP. Conclusion* We did not find a correlation between the hormonal receptor expression and stage. The place of hormonotherapy, which is increasingly used in other uterine sarcomas such as endometrial stromal sarcoma, remains to be clarified by large-scale clinical trials.

Introduction/Background* Endometrial stromal sarcoma (ESS) is a rare uterine mesenchymal tumor, accounting for 20% of all uterine sarcomas. It ranks second among uterine sarcomas, after leiomyosarcomas. These are low-grade tumors. The prognosis depends primarily on the tumor stage. Hormone receptors estrogenic and progesterone receptors (RO,RP) can help to select patients who will be treated with hormonotherapy. The objective of our work was to determine the level of expression of PRs and ROs in the ESS. Methodology Patients were selected from the computerized archives of the Department of Pathological Anatomy and Cytology of Salah Azaiez Institute. We selected 11 cases of low-grade endometrial stromal sarcomas that were diagnosed over 18 years (2002 -2020). Result(s)* ROs were expressed in 7 cases and RPs in 8 cases: a co-expression of RO and PR in 7 cases, an expression of PR only in 1 case, and a lack of expression of both markers in 3 cases. Conclusion* According to the literature, the expression ROs is found in 50 to 94% of ESS, and PR is found in 52 to 100% of ESS. Our results are comparable to those in the literature. Indeed, immunohistochemistry is currently a diagnostic and theranostic tool in ESS. The meaning of this term has been studied by many authors. It would appear that the determination of this hormonal status is useful for selecting a group of patients that are likely to respond to hormonotherapy. This hormonotherapy is much less toxic than conventional chemotherapy and could be used as adjuvant therapy or in metastatic disease.

Introduction/Background* Mucinous borderline ovarian tumors (MBT) are characterized by an epithelial proliferation similar to those of well-differentiated adenocarcinomas but are distinguished by the absence of stromal invasion. They are often difficult to diagnose histologically. On the one hand, the invasion of the stroma is not always easy to highlight, and on the other hand, the indirect criteria of invasion are not unanimously accepted. The work aims to specify the pathological and clinical features and to highlight the prognostic factors of these tumors. Methodology Our study was retrospective and descriptive including 49 cases of primary borderline mucinous tumors of the ovary, diagnosed at the Department of Anatomical Pathology and Cytology of Salah Azaiez Institute, for a period of 27 years, going from 1992 to 2019. Result(s)* The mean age of our patients was 48 years old. Histologically, the cases were divided into 34 cases of pure MBT, 13 cases with intraepithelial carcinoma, and 2 cases associating an intraepithelial carcinoma with microinvasion. The majority of our cases were classified FIGO I and only one case was FIGO III. 14 patients received conservative treatment and 32 received radical treatment. The treatment wasn’t specified in 3 patients. The progress was good in the majority of cases. Only one patient had a contralateral recurrence after a follow-up period of 3 years. There was no significant difference regarding the risk of recurrence and risk factors such as age, gestation, hormonal contraception, hormonal status, FIGO stage, presence of peritoneal pseudomyxoma, intraepithelial carcinoma, and microinvasion. Conclusion* The prognosis of TMBL depends closely on their FIGO stage, stage I tumors have a good prognosis. The presence of intraepithelial carcinoma does not influence their prognosis. However, it is necessary to multiply samples to avoid missing a carcinomatous focus with an anarchic invasion of the stroma which constitutes a poor prognosis factor.

Hepatic epithelioid angiomyolipomas are uncommon mesenchymal neoplasms. They are difficult to diagnose by imaging, especially when the fatty component is scant or absent. The gold standard for the diagnosis is histologic examination coupled with an immunohistochemical study. Positive HMB-45 immunostaining of the myoid cells is a major diagnostic feature.

Human leukocyte antigen (HLA)-G has been considered as an immune modulator in several types of cancers. Its genetic polymorphisms may potentially affect the risk of developing colorectal cancer (CRC). The overall purpose of this study was to analyze the implication of HLA-G 3′untranslated region (3′UTR) polymorphisms particularly 14 pb insertion/deletion (Ins/Del; rs371194629) and + 3142C/G (rs1063320) in CRC susceptibility and progression. A comparative analysis between patients (N = 233) and controls (N = 241) demonstrated that Del allele (Odds Ratios (OR) = 1.41, 95% CI = 1.091–1.819, p = 0.008), the homozygous Del/Del genotype (OR = 1.80, 95% CI = 1.205–2.664, p = 0.003) and the codominant C/G genotype (OR = 1.59, 95% CI = 1.106–2.272, p = 0.013) were associated to CRC risk. As expected, the DelG haplotype was associated with CRC susceptibility (OR = 1.47, 95% CI = 1.068–2.012, p = 0.018). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele and the homozygous Del/Del genotype were associated with reduced event free survival (EFS) (Respectively, p = 0.009 and p = 0.05). Interestingly, the Del allele and the homozygous Del/Del genotype have been revealed as independent prognostic factors for poor EFS in patients with CRC. Additionally, haplotypes analysis revealed that DelG haplotype was linked with significant increase in CRC risk (log-rank; EFS: p = 0.02). Inversely, the InsC haplotype was associated with a significant reduced CRC risk (log-rank; Overall survival (OS): p These findings support the implication of HLA-G polymorphisms in the CRC susceptibility suggesting HLA-G as a potent prognostic and predictive indicator for CRC. Insight into mechanisms underlying HLA-G polymorphisms could allow for the development of targeted care for CRC patients according to their genetic profile.

The stomach is the most frequent site of extranodal lymphoma. Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade, B-cell neoplasm strongly associated withHelicobacter pylori(HP) infection. The presenting complaints of gastric MALT lymphoma are usually nonspecific. HP eradication is regarded as the first-line therapy in early stage disease. Management of patients who failed to achieve remission following HP eradication include chemotherapy, radiotherapy and in selected cases, surgery. The aim of the present study was to examine the clinical characteristics and treatment outcome of patients with gastric MALT lymphoma.

Prenatal diagnosis of neonatal hemochromatosis (NH) is usually raised in front of fetal hepatomegaly and heterogeneous liver architecture. We describe a novel sonographic feature that may be associated with NH. Ultrasound demonstrated reticulonodular liver and distended gallbladder with multiple gallstones in a hydropic fetus. These abnormalities were confirmed to be consistent with NH after correlation with autopsy findings. This case report highlights the value of cholelithiasis in clinical suspicion of NH and the importance to consider this sonographic feature when the liver has abnormal texture.

Endometrial cancer is the most prevalent genital tract cancer in occident and the third most common cancer among women in Tunisia. It is dominated by carcinoma. The identification of prognostic factors allows a better understanding of its outcome and guides its therapeutic approach. We propose to describe the clinicopathological features and identify the histoprognostic factors of this cancer. It is a retrospective analysis of a series of 62 total hysterectomy specimens with bilateral salpingo-oophorectomy from women with primary carcinoma of the endometrium, colligated in Anatomy Laboratory and Pathology Salah Azaiz Institute of Tunis over a period of 5 years, from January 2003 to December 2007. The median age was 60 years. At the time of diagnosis, 25% of patients were nulliparous and 86% were menopaused. The endometrioid adenocarcinoma was the most common, accounting for 84% of cases (5% of them were grade 3). A myometrial invasion superior or equal to 50% was observed in 40% of cases. 42% of cases were classified as stage IA, 14% in stage IB, 16% in stage II, 18% stage III and 10% in stage IV. 22% of patients had nodal involvement. Overall survival at 5 years was 81%. In multivariate analysis, stage IV, nodal involvement and brachytherapy have influenced this rate. Event-free survival at 5 years was 71%. It was directly related to stage and nodal involvement. Stage, histological type, tumor grade, invasion of more than half of the myometrium and lymph node involvement were the most important adverse prognostic factors, dictating an appropriate management of these tumors.

Alveolar soft-part sarcoma (ASPS) is an uncommon, aggressive soft-tissue neoplasm, occurring in less than 1% of sarcomas. It is typically found in the head and neck tissues in children or in the deep soft tissues of the lower extremities in young adults. This tumor arises primarily within the skeletal muscles or musculofascial planes. Primary involvement of bone is extremely rare. ASPS has poor prognosis with a propensity for recurrence as well as distant metastasis. In this report, we present a 25-year-old male with primary ASPS in the left scapular bone and discuss the histopathological and immunohistochemical features of this sarcoma.

DNA mismatch repair (MMR) deficiency is associated with increased risk of developing several types of cancer and is the most common cause of hereditary endometrial cancer. Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are frequent.The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI status in endometrial carcinoma and evaluate the correlation between the MSI phenotype and the various anatomo-clinical parameters.IHC expression of 4 markers (MLH1, MSH2, PMS2, and MSH6) was studied. For all IHC markers, a combined score based on the intensity of nuclear labeling and the percentage of labeled cells was defined to establish a score. Correlation between MSI phenotype and different clinicopathologic parameters was evaluated using statistical analysis (software STATA and the Fisher exact test).The mean age of the patients was 58.6 years. Positive staining was highly extended (score 3) with 79% to 100% of marked cells. Less than 10% of positive tumor cells were seen in 3% of cases for MSH6 and PMS2. Abnormal MMR IHC was detected in 10 cases (22.22%). Seven tumors showed loss of MLH1/PMS2. The loss of MSH2/MSH6 was observed in 1 case. The loss of MLH1 or PMS2 was seen only in 2 cases. The number of MSI positive status was 10 cases (22.7%). Correlation between clinicopathologic parameters showed MMR deficiency was significantly associated with low-grade tumor and localized stage. There was no positive correlation between age, histologic subtype, or myometrium invasion.In summary, detection of DNA MMR deficiencies by IHC can effectively diagnose the MSI phenotype in endometrial carcinoma. Correlation between clinicopathologic parameters showed MMR deficiency was significantly associated with low-grade tumor and localized stage.

Objectives To evaluate the role of lymphadenectomy in advanced epithelial ovarian cancer (EOC). Methods Data of 121 patients who underwent surgery for FIGO staged IIB-IV EOC between 2000 and 2010 were retrospectively reviewed. Results Primary debulking surgery was performed in 96 patients and interval debulking surgery in 25 cases. Maximal cytoreduction (R0) was achieved in 37 of patients (30.6%), 39 patients had a residual disease ≤1 cm (32.2%) and 45 had a residual disease Conclusions Lymphadenectomy is associated with a better survival in patients with advanced ovarian cancer.