Clinicopathological and prognostic significance of DNA mismatch-repair protein expression in gastric adenocarcinoma

Although the significance of DNA mismatch repair (MMR) protein expression in colorectal cancer is well-established, it remains contentious in extra-colorectal cancers and mainly in gastric adenocarcinoma. Data from Africa and Arab world remain limited. This study explored the MMR expression in gastric adenocarcinoma and evaluated its clinicopathological and prognostic signification among Tunisian patients. A retrospective study of 72 gastric adenocarcinomas was carried out. Clinicopathological particularities and patient outcomes were recorded. MMR expression was determined by immunohistochemistry on whole sections of archived material. Survival analysis was realized utilizing the Kaplan-Meier estimates and Log-Rank test. Expression of MMR proteins was observed in 84.7% of gastric adenocarcinoma samples. The 11 remaining samples (15.3%) exhibited an altered pattern of MMR protein. A significant association was identified between deficient MMR expression and advanced age (p = 0.03), intestinal type (p = 0.04) and lymph node metastases (p = 0.04). No other significant relationship was observed with the remaining selected tumor features. Patient survival was significantly associated with lymph node invasion (p = 0.002), distant metastases (p = 0.02) and tumor differentiation (p = 0.03), but not with MMR status (p = 0.83). MMR deficiency was related to advanced-age, intestinal type and nodal metastasis, but not to survival of Tunisian patients with gastric adenocarcinoma. Larger multicenter studies with additional molecular investigation are required to more explore these tumors.

Bien que l'importance de l'expression des protéines de réparation des mésappariements de l'ADN (MMR) dans le cancer colorectal soit bien établie, elle reste controversée dans les cancers extra-colorectaux et principalement dans l'adénocarcinome gastrique. Les données de l'Afrique et du monde arabe restent limitées. Cette étude a exploré l'expression des protéines MMR dans l'adénocarcinome gastrique et a évalué sa signification clinicopathologique et pronostique chez les patients tunisiens. Une étude rétrospective de 72 adénocarcinomes gastriques a été réalisée. Les particularités clinicopathologiques et pronostiques des patients ont été enregistrées. L'expression des protéines MMR a été déterminée par immunohistochimie. L'analyse de survie a été réalisée en utilisant la méthode de Kaplan-Meier et le test Log-Rank. L'expression des protéines MMR a été observée dans 84,7 % des échantillons d'adénocarcinome gastrique. Les 11 cas restants (15,3 %) présentaient un profil d'expression altérée des protéines MMR. Une association significative a été identifiée entre l'expression déficiente de MMR et l'âge avancé (p = 0,03), le type intestinal (p = 0,04) et les métastases ganglionnaires (p = 0,04). Aucune autre relation significative n'a été observée avec les autres caractéristiques tumorales sélectionnées. La survie des patients était significativement associée à l'envahissement des ganglions lymphatiques (Log Rank, p = 0,002), aux métastases à distance (Log Rank, p = 0,02) et à la différenciation tumorale (Log Rank, p = 0,03), mais pas à l'expression de MMR (Log Rank, p = 0,03). Rang, p = 0,83). Le déficit de l'expression des protéines MMR était lié à l'âge avancé, au type intestinal et aux métastases ganglionnaires, mais pas à la survie des patients tunisiens ayant un adénocarcinome gastrique. Des études multicentriques avec des investigations moléculaires supplémentaires sont nécessaires pour explorer davantage le cancer gastrique avec expression déficiente des protéines MMR.

Inhabitual presentation of Sertoli-Leydig cell tumor of the ovary with xeroderma pigmentosum: Case report with review of literature.

INTRODUCTION: Sertoli-Leydig cell tumors (SLCTs) are rare sex-cord stromal tumors of the ovary. Heterologous components may be present, most commonly in the intermediate differentiated and poorly differentiated groups. Because of their scarcity, SLCTs with heterologous differentiation represent a challenge in both diagnosis and management, with limited available experience. PRESENTATION OF CASE: We report a case of a 27-year-old, Tunisian woman, followed in the Dermatology Department since the age of six months for xeroderma pigmentosum, with a history of basal cell carcinoma of the face operated on several times. The patient presented with abdominal pain and bloating associated with a medium abundance ascites on physical exam. Ultrasound showed a large left adnexal mass associated with an elevated cancer antigen 125 on serological exam. The patient underwent unilateral salpingo-oophorectomy with resection of two omental nodules. Microscopic examination concluded to poorly differentiated Sertoli-Leydig tumor with rhabdomyomatous differentiation. Adjuvant chemotherapy was performed and there was no clinical evidence of tumor recurrence during the three years of follow-up. DISCUSSION: SLCTs with rhabdomyomatous differentiation on the setting of xeroderma pigmentosum are exceptional, microscopic diagnosis and management is challenging, considering the tumor scarcity. CONCLUSION: Further case reports and retrospective studies are required to more understand the pathogenesis of SLCTs and to determine their optimal treatment regimen.

Signification of forkhead box A1 (FOXA1) expression in thyroid cancers.

BACKGROUND: Forkhead box A1 (FOXA1) plays an important role in several tumors. This study investigated the potential role of FOXA1 expression in thyroid tumors. We conducted a retrospective study of 110 thyroid lesions and tumors diagnosed during 1995-2018. The expression of FOXA1 was analyzed by immunohistochemistry on archival material. RESULTS: No FOXA1 immunostaining was observed in all cases of Graves' disease, Hashimoto's disease, multi-nodular goiter, and adenoma. FOXA1 expression was absent as well in all papillary and follicular carcinomas, Hurthle cell carcinoma, and undifferentiated sarcoma. Only three anaplastic carcinomas exhibited focally FOXA1 staining. However, FOXA1 was expressed in all medullary carcinomas. No significant correlation was found with all clinicopathological features (p > 0.05 for all). The pattern of FOXA1 staining was similar to that of calcitonin and chromogranin A (p = 0.04 and p = 0.003, respectively). CONCLUSIONS: FOXA1 is expressed mostly in all medullary thyroid carcinomas. Hence, FOXA1 could serve as an additional marker for refining the diagnosis of medullary thyroid carcinoma.

HPV infection and p16INK4A and TP53 expression in rare cancers of the uterine cervix.

Cervix cancer remains among most commonly diagnosed cancer in developing countries. Except squamous cell carcinoma and adenocarcinoma, the etiopathology and oncogenic mechanisms of rare cancers remain largely unknown. The study was performed to investigate the value of HPV infection and the expression of p16INK4A and TP53 in rare primitive cancers of the cervix. We conducted a retrospective study of rare primitive cancers of the cervix. Main clinicopathological features were reported. HPV infection was detected by in situ hybridization. Expression of p16INK4A and TP53 was analyzed by immunohistochemistry. Overall, seven cases were identified, including basaloid squamous cell carcinoma (BSCC, n = 2), small cell neuroendocrine carcinoma (SCNEC), granulocytic sarcoma without acute myeloid leukemia, leiomyosarcoma, primitive neuroectodermal tumor and botryoid-type embryonic rhabdomyosarcoma. The mean age of patients was 53.7 years. Four cancers were diagnosed at advanced stages. The prognosis was unfavorable and associated with patient death in five cases. HPV types 16/18 were detected in BSCCs and SCNEC. Strong and diffuse p16INK4A overexpression was described in the nucleus and the cytoplasm of all tumor cells of BSCCs and SCNEC. The remaining cancers exhibited only scattered and focal p16INK4A staining. Mutated TP53 protein was detected in BSCC (case 1) and GS. Rare cancers of the cervix are aggressive and associated with poor prognosis. In contrast to mesenchymal tumors, BSCCs and SCNEC are etiologically related to high-risk HPV infection and could be identified by block positive p16INK4A overexpression as common cancers of the cervix. TP53 mutations are not a negligible genetic event in rare cervical cancers.

Breast cancer in the Maghreb : epidemiology and control strategies. Review.

Breast cancer is the most common cancer diagnosed in women in the Maghreb and around the world. It's the most common cause of cancer deaths. It represents a major public health problem because of its frequency, morbidity and mortality that it generates as well as the cost of the therapies used. Epidemiological data are similar in the 3 countries of the Maghreb (Tunisia, Morocco, and Algeria). Currently, the incidence of breast cancer is lower than in developed countries, but is increasing steadily, and projections for the coming years predict that rates will be closer to the European ones. The diagnosis is often done at advanced stages compromising the prognosis of the patients. Strategies to combat this cancer remain insufficient and further efforts are needed to improve the situation.