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Background. Because of its high metastatic potential, inflammatory breast cancer (IBC) is the most lethal and aggressive form of breast cancer. We previously demonstrated that Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) protein overexpression was associated with shorter metastasis-free survival (MFS) in IBC patients, but not in non-IBC (nIBC) patients. However, the mechanism of action of MARCKS and its particular association to poorer outcome in IBC compared to nIBC are poorly understood. Methods. We evaluated in vitro the inhibitory effect of MPS (MARCKS phosphorylation site domain), a peptide targeting MARCKS phosphorylation site domain (PSD) in single and in combination with paclitaxel treatment, on cell proliferation and cell motility in two cell lines of different phenotype (SUM149 for IBC and MDA-MB-231 for nIBC), as well as its distinct molecular mechanisms of action. We also assessed the clinical relevance of the protein expression of MARCKS and phosphatase and tensin homolog (PTEN) in a large series of IBC vs. nIBC patients. Results. In vitro, the treatment with MPS peptide impaired cell proliferation, migration, and invasion in SUM149 compared to MDA-MB-231 cells. More important, MARCKS inhibition increased paclitaxel sensitivity when using combination therapy in SUM149 cells compared to MDA-MB-231 cells. Interestingly, we could partially explain this specific inhibitory effect in IBC cells using western blot: MARCKS inhibition in single and in combination induced up and downregulation of the PTEN/AKT signaling pathway respectively in IBC compared to nIBC cells. Importantly, a negative correlation of MARCKS and PTEN was only found in the clinical IBC samples (180 patients) compared to nIBC samples (355 patients). More importantly, the group of patients with negative MARCKS and positive PTEN protein expression was associated to better 5-year MFS only in IBC patients. Conclusion. These results indicate two major findings: first, the important prognostic value of the negative correlation of MARCKS and PTEN expression in IBC patients, and second the specific role of MARCKS in regulating different downstream pathways and increasing the paclitaxel response in combination treatment in IBC compared to non-IBC. They suggest a potential IBC-specific targetable biomarker, the inhibition of which might impair disease aggressiveness and perhaps enhance patients’ survival. Citation Format: Maroua Manai, Ines Bini, Pascal Finetti, Haifa Bichiou, Carolina Reduzzi, Naziha Ben Hamida, Marc Lopez, Khaled Rahal, Karima Mrad, Mohamed Manai, Massimo Cristofanilli, Hamouda Boussen, Raoudha Doghri, Maher Kharrat, François Bertucci. Targeting MARCKS in inflammatory breast cancer increased paclitaxel sensitivity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-15.

Osteoarticular manifestations such as arthritis and bone pain are scarce among adults with acute lymphoblastic leukemia (ALL). We present a systematic review of osteoarticular first clinical manifestation related to ALL in adults, and we report a case of an adult patient with a B-cell ALL revealed by refractory pygalgia and arthritis. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE database, including case reports and case series describing osteoarticular manifestations revealing ALL in adults. There were 29 patients with osteoarticular manifestations, revealing ALL (including our case). The mean age was 34.00 ± 13.29 years. Osteoarticular manifestations were peripheral articular signs (7 cases), axial manifestations (17 cases), and osteolytic lesions (21 cases). Vertebral fractures were reported in 4 cases. MRI was performed in 15 cases, showing heterogeneous signal changes in the vertebra, skull, and sacroiliac bones. It showed avascular necrosis of the femoral head in one case. PET scan, performed in 7 cases, showed diffuse or localized FDG uptakes in the bone marrow. Hypercalcemia was noted in 9 cases. The treatment was based on chemotherapy (23 patients) and radiotherapy (4 cases). During the follow-up, remission was noted in 14 cases, death in 9 cases, and was not available in 6 patients. Our review showed that axial manifestations, joint swelling, bone pain, and hypercalcemia could be the first and only symptoms of ALL in adults, making the diagnosis of ALL difficult to recognize, leading to a diagnosis delay. Key Points • Acute lymphoblastic leukemia in adults revealed by osteoarticular manifestations can be misdiagnosed as rheumatic diseases. • Axial manifestations, joint swelling, bone pain, and hypercalcemia could be the first and only symptoms of acute lymphoblastic leukemia in adults. • Complete blood count and calcium blood test should be performed as first-line investigations in adults with axial or peripheral articular symptoms. • Physicians should be aware of this clinical presentation to avoid diagnosis delay and improve prognosis.

Background Cervical cancer (CC) remains one of the most common malignancies in women worldwide. The immune checkpoint PD-L1 is one of the important players in immunosuppression in the tumor microenvironment of CCs. The objectives of the present study were to determine the expression profile of the PD-L1 protein in CC by immunohistochemistry and to study the correlations between the PD-L1 status and the clinicopathological and prognostic characteristics. Methods This was a retrospective descriptive study of 146 cases of CCs, collected at the pathological department of Salah Azaiez Institute from medical records and pathological reports. Immunohistochemistry was used to assess the expression of PD-L1 according to the protocol applied in the laboratory. Results The average age of the patients was 54 years (23-87 years). The mean tumor size was 40.7 mm (5-90 mm). The most common histological type was squamous cell carcinoma (88.3%). CCs were well differentiated in 62.6% of cases. Stage 2B was observed in 49% of cases. Vascular emboli were observed in 7.1% of cases. Concomitant radio-chemotherapy was recommended in 86.8% of the patients and brachytherapy was indicated in 79.7% of the patients. More than half of the patients were operated. Occurrence of distant recurrence was observed in 17.3% and pelvic recurrence in 20.4% of the cases. The evolution was favorable in 39.3% cases. Immunohistochemical analysis revealed PD-L1 expression in 32.4% in tumor cells and in 47.1% in the immune cells. The expression of PD-L1 in tumor cells was associated to endometrium invasion (p=0.014). Conclusion PD-L1 is expressed in CCs. No association with histoprognostic parameters has been demonstrated. Larger studies should be considered with a high number of samples to assess the correlation between PD-L1 and histoprognostic factors to support the role of this biomarker in the evolution of CCs.

Background: Multiple sclerosis (MS) is characterized by a combination of inflammatory and demyelination processes in the spinal cord and brain. Conventional drugs generally target the autoimmune response, without any curative effect. For that reason, there is a great interest in identifying novel agents with anti-inflammatory and myelinating effects, to counter the inflammation and cell death distinctive of the disease. Methods and results: An in vitro assay showed that curcumin (Cur) at 10 µM enhanced the proliferation of C8-D1A cells and modulated the production of Th1/Th2/Th17 cytokines in the cells stimulated by LPS. Furthermore, two in vivo pathophysiological experimental models were used to assess the effect of curcumin (100 mg/kg). The cuprizone model mimics the de/re-myelination aspect in MS, and the experimental autoimmune encephalomyelitis model (EAE) reflects immune-mediated events. We found that Cur alleviated the neurological symptomatology in EAE and modulated the expression of lymphocytes CD3 and CD4 in the spinal cord. Interestingly, Cur restored motor and behavioral deficiencies, as well as myelination, in demyelinated mice, as indicated by the higher index of luxol fast blue (LFB) and the myelin basic protein (MBP) intensity in the corpus callosum. Conclusions: Curcumin is a potential therapeutic agent that can diminish the MS neuroimmune imbalance and demyelination through its anti-inflammatory and antioxidant effects.

Introduction:ovarian Mucinous Borderline 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. The aim of the work was to specify the pathological and clinical features and to highlight the prognostic of these tumors. Methods:study was retrospective including 49 cases of primary ovarian MBT, diagnosed at the Patholgy Department of Salah Azaiez Institute from 1992 to 2019. Results:median age 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 FIGO III. Sixteen patients received conservative treatment and 30 received radical treatment. The treatment wasn’t specified in three patients. The prognosis was good in the majority of cases. Only one patient had a contralateral recurrence after a follow-up period of three years. There were no significant difference regarding the risk of recurrence and risk factors such as age, gestation, hormonal status, FIGO stage and conservative treatment. We raised this part. Conclusion:the prognosis of the ovarian MBT is good. However, it is necessary to multiply the samples to avoid missing a carcinomatous focus with an anarchic invasion of the stroma which constitutes a poor prognosis factor. It was changed by these sentences below: the diagnosis of MBT is not easy. Indeed, the distinction of MBT from carcinomas remains the greatest challenge for pathologists. Once this diagnosis is made with certainty, the tumor can be considered to have a good prognosis, especially stage I tumors which are the most common.

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.

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.

Intravenous leiomyomatosis of the uterus (IVL) is a rare type of uterine leiomyoma. It is defined by the presence of benign smooth muscle within vascular spaces outside the confines of a leiomyoma, free floating within the lumen or adherent to the vessel wall.

Langerhans cell histiocytosis (LCH) is a rare disorder of unknown etiopathogenesis. Diagnosis is based on the identification of CD1a positive histiocytic infiltrate. Activation of the mitogen-activated-protein-kinase (MAPK) is constantly observed in LCH and therefore downstream markers such as cyclin D1 may be a useful marker for LCH. The aim of this study was to investigate the expression of cyclin D1 in LCH. We assessed the immunohistochemical expression of cyclin D1 (clone SP4-R) in series of 16 cases of confirmed LCH. Expression of Cyclin D1 was scored as weak, moderate, and strong nuclear staining and results were interpreted by two pathologists. The percentage of positivity was assessed. The mean age of patients was 13.7 years old with a male to female ratio of 1:3. The most common involved site was bone (n = 9; 56,3%), followed by lymph node (n = 5; 31,2%) and skin (n = 2; 12,5%). All cases showed nuclear staining for cyclin D1 with variable intensity. It was assessed moderate in 43,8% (n = 7) and strong in 56,2% (n = 9). The percentage of positive cells was50% in 13 cases and50% in 3 cases. Our results have shown that all cases of Langerhans cell histiocytosis from various sites express cyclin D1. This finding may be attributed to MAPK pathway activation that has been described in LCH. Otherwise, cyclin D1 is not significantly expressed in reactive Langerhans cell proliferations. Therefore, cyclin D1 immunohistochemistry may be useful as a diagnostic marker and in excluding non-neoplastic mimics of LCH.

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.

The adverse health effects of benzene occupational and circumstance pollution exposure are an increasing concern. It leads to damage to various human tissues including bone marrow and ovarian tissues and many vital physiological processes. Previous studies showed that kefir is a rich probiotic, having protective effect, thanks to its antioxidant, anti-inflammatory, and immunomodulatory capacity. The purpose of this study was to evaluate the potential efficacy of kefir to remediate benzene toxicity in rat. Thirty-two female rats were randomly allocated and administered orally with benzene and/or kefir during a period of 21 consecutive days. At the end of the experiment, hematological and bone marrow cell changes were estimated. The animals exposed to benzene exhibited anemia and a significant decrease in the levels of white blood cell. Moreover, benzene led to the activation of gene expression of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6), a myelotoxicity in bone marrow cells. Our data showed that kefir treatment alleviated benzene-associated weight loss and increased the number of whole blood cells in peripheral blood and nucleated cells in the bone marrow. Furthermore, these physiological results were observed with animals showing high concentrations of lactic acid bacteria (LAB) determined from fecal samples, which are considered an indicator of kefir-associated microorganisms. Our study suggests that kefir is a potential nutritional supplement target to attenuate hematotoxicity induced by benzene.

Introduction Sex cord tumor with annular tubules (SCTAT) represents less than 1% of ovarian neoplasms. It includes two forms; a form associated with Peuz-Jeghers syndrome (PJS) which is usually benign, and the other one, sporadic, with malignant behavior. We aim to study the clinical, radiological, and pathological particularities of SCTAT. Methods We report four cases of SCTAT treated in Salah Azaiz Institute of Oncology, Tunis, Tunisia between 2000 and 2013. Results The average age was 30 years, ranging from 4 to 76 years. The age of our patients ranged from 10 to 32 years. One of our patients had a concomitant diagnosis of PJS. The tumor was unilateral in all cases and was revealed by precocious puberty in one case. Gross findings showed a solid tumor, with a yellow cut surface. The size ranged from 0,5 to 28 cm. The morphological features were characteristic but intermediate between granulosa and Sertoli cells. Immunohistochemistry showed that tumor cells expressed inhibin and calretinin. The treatment was surgical, often conservative. The diagnosis of malignancy wasn’t focused on histological features, but on tumor extension, clinical course, and presence of metastases. Conclusion SCTAT is a rare tumor, usually benign. The diagnosis is based on histological examination. Malignant potential is noted in sporadic forms. Surgery remains the corner stone of the treatment which is most often conservative, based on oophorectomy.

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.

A novel decavanadate compound, Mg(H2O)6(C4N2H7)4V10O28·4H2O, was synthesized by slow evaporation at room temperature and characterized through single crystal X-ray diffraction, SEM-EDX, IR spectroscopy. The compound crystallizes in a monoclinic system, P21/n space group with a=10.661(5) A, b=21.256(9) A, c=10.767(5) A, β=102.82(4), Z=2 and a volume of 2379.13(2) A3. The compound structure consists of centrosymmetric decavanadate groups, Mg(H2O)6 polyhedral, (C4N2H7)+ cations and water molecules linked through N-H…O and O-H…O hydrogen bonds. The three-dimensional Hirshfeld surface (3D-HS) and the relative two-dimensional fingerprint plots (2D-FP) revealed that the structure is dominated by H…O/O…H and H…H interactions. When injected to mice by intraperitoneal route, Mg(H2O)6(C4N2H7)4V10O28·4H2O showed toxicity only at a high dose (5 mg/kg), as revealed by clinical and biochemical results, as well as histological examination of mice's liver and kidney. Interestingly, the synthetic compound inhibited the growth of three invasive cancer cell lines; U87 (glioblastoma), IGR39 (melanoma) and MDA-MB-231(triple negative breast cancer) by a dose dependent manner with an IC50 values of 2 µM for both U87 and MDA-MB-231 cells and 3 µM for IGR39 cells. Therefore, we could consider that Mg(H2O)6(C4N2H7)4V10O28·4H2O opens up a window toward the conception of potential organo-metalic dugs with antitumoral properties.

Glassy cell carcinoma is a rare neoplasm that occurs most frequently in the uterine cervix. We describe the second reported case of glassy cell carcinoma arising in the vagina. We present a case of a 24-year-old woman with a history of post-coital bleeding associated with menometrorrhagia. Different explorations have concluded in a glassy cell carcinoma arising in the vagina, with clinical staging III according to the International Federation of Obstetrics and Gynecology. The patient received three cycles of neoadjuvant chemotherapy with a good response. Then she had a para-aortic lymphadenectomy and ovarian transposition. Following the surgery, she had radiotherapy. The gynecological examination showed no budding lesion and the biopsy was negative. Six months later, the patient complained of a pelvic pain. The examination revealed a locoregional recurrence. Surgical revision was not possible and the patient was a candidate for a palliative chemotherapy. Although, glassy cell carcinoma runs an aggressive clinical course, an early diagnosis may help in a more effective management and offer a better prognosis.

International audience; Background: Epithelial ovarian cancer (EOC) is the major gynecological cause of cancer deaths. Annexin A1 (ANXA1) protein has been implicated in the aggressiveness of several cancer types.Materials and methods: This study retrospectively assessed ANXA1 expression in epithelial cells of 156 pre-chemotherapy EOC samples and 34 normal ovarian samples from patients treated at Salah Azaiez Institute. Using immunohistochemistry, ANXA1 expression was compared in normal versus cancer samples; correlations with clinicopathological features, including overall survival, were sought.Results: Fifty-two percent of tumor samples showed epithelial ANXA1 staining versus only 26% of normal samples (Fisher's exact test, p=0.00794). Epithelial ANXA1 expression was correlated with better overall survival in both univariate and multivariate analyses.Conclusion: The possible contribution of ANXA1 overexpression to EOC outcome may be relevant to therapeutic strategies.

Introduction/Background Non-epithelial ovarian tumors represent an heterogeneous group of rare ovarian cancer. The aim of this study was to describe the clinico-pathological features and treatment of those malignancies in a Tunisian single center. Methodology Medical records of 134 patients with non-epithelial ovarian tumors treated between 1980 and 2010 were reviewed. Data collected included clinical features, treatment modalities and prognostic indicators. Results Overall, 94 were germ cell tumors (70%) and 40 sex cord-stromal tumors (30%). Thirty-six (27%) had immature teratoma, 28 (21%) had dysgerminoma, 13 (10%) had mixed germ cell tumors, 12 (9%) had yolk sac tumor, 5 (4%) had embryonal carcinoma, 37 (27%) had adult granulose cell tumors, 2 (1.5%) had juvenile granulose cell tumors and one (0.5%) had leydig and sertoli cells tumor. Median age at diagnosis was 28 years (range 7–95). Mean age was 27 for immature teratoma, 18 for dysgerminoma, 21 for mixed germ cell tumors, 23 for yolk sac tumor, 13 for embryonal carcinoma, 52 for adult granulose cell tumors and 24 for juvenile granulose cell tumors. Ninety-four (70%) presented with abdominal mass and/or pain. Surgery was the first treatment for 99% (n=133) with fertility sparing management in 79%. FIGO staging was as follows: Stage I in 63% (n=84) (stage IC: 23% of stage I), stage II in 6% (n=8), stage III in 24% (n=32), and stage IV in 7% (n=10). Sixty-four (48%) received adjuvant chemotherapy. Median follow-up period was 45 months. The 5-year odds survival was 78%. Reccurence occurred in 18% (n=24).The 5-years disease free survival was 75%. Conclusion As it is usually unilateral and chemosensitive with high incidence in young women, fertility-sparing surgery with optimal staging should be the standard of care of non-epithelial ovarian cancer. Disclosure Nothing to disclose.

Introduction/Background Non-epithelial ovarian tumors are uncomm malignancies which can be extremely challenging to treat. The aim of the study was to evaluate the effectiveness of chemotherapy in women with early stage disease. Methodology Medical records of 84 patients diagnosed with stage I non epithelial ovarian cancer between 1985–2015 were reviewed. Tumor characteristics and treatment receipt were described. Results Median age was 28 years [9–95]. Sixty-five had stage Ia disease at diagnosis while 19 presented with stage Ic disease. Fourteen had dysgerminoma (16.7%), 30 had immature teratoma (35.7%), 5 had yolk sac tumor (6%), 3 had embryonal carcinoma (3.6%), 3 had mixed germ cell tumor (3.6%), 28 had adult granulose cell tumor (33.3%) and one had juvenile granulose cell tumor (2.4%). Most of them (n=55, 65%) underwent fertility sparing surgery. Thirty-one (37%) received adjuvant platinum based chemotherapy, among them 17/65 were stage Ia disease and 14/19 were stage Ic disease. Fifty-two (62%) had surgery followed by active surveillance. Fertility sparing surgery was followed by adjuvant chemotherapy in 25% (n=21). After a median follow up of 45 months, 14 relapsed. Among them 6 received adjuvant chemotherapy and 8 underwent surgery followed by surveillance. The 5-year-disease-free-survival (DFS) and 5 year overall survival (OS) were respectively 79% and 46% in the chemotherapy arm and 80% and 51% in the surveillance arm with no statistically significant difference observed in DFS (p=0.4) and OS (p=0.3). Conclusion Fertility sparing surgery with active surveillance is an option which should be discussed within a multi disciplinary team especially in young patients with early stage disease desirous of pregnancy. Disclosure Nothing to disclose.

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.