Clinical characteristics and survival outcome of early-stage, high-grade, serous tubo-ovarian carcinoma according to BRCA mutational status.

OBJECTIVE: To investigate the role of BRCA1/2 mutations in early ovarian cancer (eOC) (International Federation of Gynecology and Obstetrics FIGO 2014 stage I-II), and its impact on prognosis after relapse. METHODS: In this multicenter retrospective study, clinical and survival data from high-grade serous (HGS)-eOC patients at presentation and recurrence were compared according to BRCA status: BRCA-mutated (BRCAmut) vs. BRCA wild-type (BRCAwt). RESULTS: Among 191 HGS-eOC patients, 89 were BRCAmut and 102 BRCAwt. There was no significant difference according to the BRCA status in terms of Progression-Free Survival (PFS). A longer Overall Survival (OS) was found in BRCAmut patients. Stage I patients had significantly improved PFS vs stage II, regardless of BRCA status. At multivariate analysis, stage at diagnosis was the only variable with a significant effect on PFS. No factors were significantly relevant on OS, albeit younger age and BRCA mutation showed a slight impact. Post-Recurrence Survival (PRS) in the BRCAmut population was significantly improved compared with BRCAwt. At multivariate analysis, Secondary Cytoreductive Surgery was the strongest predictor for longer PRS, followed by PARPi maintenance at recurrence. CONCLUSIONS: BRCA-status is not a prognostic factor in early ovarian cancer regarding PFS. However, our data suggest a better prognosis after relapse in BRCAm population.

Role of fertility-sparing surgery and further prognostic factors in borderline tumors of the ovary.

OBJECTIVE: Borderline tumors of the ovary are a rare group of ovarian neoplasms with distinctive histological features. Considering their favorable prognosis and occurrence at a younger age, fertility-sparing surgery may be considered. Several risk factors have been identified as contributing to a higher recurrence rate, while the impact of pathohistological features varies in the literature. This study aimed to analyze risk factors for recurrence in patients with borderline tumors of the ovary. METHODS: Analysis included patients treated with first diagnosis of a borderline tumor at our center between January 1997 and December 2022 to analyze disease-free survival and to identify the role of fertility-sparing surgery, defined as preservation of at least one ovary, pathohistological features, and other prognostic factors for relapse. All stages classified according to the International Federation of Gynecology and Obstetrics (FIGO) were included. RESULTS: Among 507 patients, 26 patients (5.2%) had a recurrence, with 21 (4.1%) showing borderline histology and 5 (1%) with invasive relapses. Recurrence rate was higher following fertility-sparing surgery (p<0.0001). Median follow-up period was 49.2 (range 42.0-57.6) months. Among 153 patients (30.2%) who had fertility-sparing surgery, 21 (13.7%) experienced a recurrence (including one invasive relapse). Fertility-sparing surgery (HR 20; 95% CI 6.9 to 60; p<0.001), FIGO stage I with bilateral presence of tumor (HR 6.4; 95% CI 1.3 to 31; p=0.020), FIGO stage II (HR 15; 95% CI 3.4 to 68; p<0.001), FIGO stages III-IV (HR 38; 95% CI 10 to 140; p<0.001) in comparison with FIGO stage I with unilateral tumor, microinvasion (HR 8.6; 95% CI 2.7 to 28; p<0.001), and micropapillary growth patterns (HR 4.4; 95% CI 1.8 to 10; p=0.001) were identified as independent risk factors for recurrence in multivariate analysis. None of these factors were associated with an increased risk of disease-related death. CONCLUSIONS: Our study showed that although a fertility-preserving approach is associated with increased recurrence rates of a borderline tumor, it does not affect overall survival and can therefore be regarded as oncologically safe for patients desiring to preserve fertility. Additionally, presence of micropapillary patterns and microinvasion were identified as prognostic risk factors.

PARP inhibitors (PARPi) prolongation after local therapy for oligo-metastatic progression in relapsed ovarian cancer patients.

BACKGROUND: PARP inhibitors (PARPi) have revolutionized the management of high-grade epithelial ovarian cancer (HGOC) treatment. However, a significant number of patients relapse or progress under PARPi, leading to the introduction of a new line of systemic therapy such as chemotherapy. In patients with a limited number of metastatic sites at progression, -referred to as an oligometastatic progression- a potential indication for local therapy followed by re-introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of such strategies on progression free survival (PFS) in these patients remains unknown. METHODS: This international multicenter retrospective study evaluated the efficacy of PARPi continuation or re-introduction in patients with HGOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and overall survival (OS). RESULTS: 74 patients were identified in 20 centers between April 2020 and November 2021. 65% of patients were BRCA mutated and 92% had received ≥2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (27%), liver (16%), other visceral (16%) and abdominal wall (4%). Local therapies included radiotherapy (45%), surgery (43%), both (7%), percutaneous thermal ablation (4%) or chemoembolization (1%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After a median follow up of 14.8 months, 6 patients (8.1%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0]. CONCLUSIONS: With close to one year without progression or introduction of a new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi.

Long term follow-up after minimally invasive sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is a benign condition that can adversely affect women's quality of life. Minimally invasive mesh sacrocolpopexy is an effective surgical treatment for POP. This study aims to assess the perioperative, postoperative, and long term (10 years) outcome of a single institution cohort undergoing minimally invasive sacrocolpopexy. METHODS: This retrospective study included all cases of laparoscopic sacrocolpopexy performed between 2003 and 2016. Patients were contacted by phone in 2022 for long term follow-up. Data on operative time, length of hospital stay, conversion rate, perioperative injuries, early and late postoperative complications and subjective success rates were collected. RESULTS: Ninety-five patients were included aged 60±12 years. Most patients (72%) presented grade 3 POP. Grade of prolapse (3±0.4 vs 3±0.5, p<0.01) and hospital stay (3±1.1 vs 3.1±1.7; p<0.01) were significantly higher in patients who developed early postoperative complications (1st year). At long term follow-up (12±3 years), 48 patients responded. Nine subjects (19%) presented a subjective recurrence with bulge symptoms. Surgery satisfaction was of 79%. The most frequent de novo reported symptom was urge urinary incontinence followed by stress urinary incontinence. Three cases (3%) of mesh erosion were described, all occurred after the 5th postoperative year. CONCLUSIONS: Laparoscopic mesh sacrocolpopexy is a safe surgical technique that shows satisfying and consistent long-term results despite the occasional onset of new urinary symptoms.

Validation of the Human Papillomavirus Impact Profile in Lebanese Women With Human Papillomavirus or Associated Lesions.

OBJECTIVES: Human papillomavirus (HPV) is responsible for a multitude of lesions with high psychosocial burden. The "HPV Impact Profile" (HIP) questionnaire is one of the first and most specific tools evaluating the emotional impact of HPV. This study aimed to translate this questionnaire into Arabic and to validate it, in a sample of Lebanese female patients. MATERIALS AND METHODS: The HIP questionnaire was translated to Arabic. It was then administered to 118 Lebanese women infected with HPV or screened for HPV-associated lesions, in parallel with the Hospital Anxiety and Depression Scale questionnaire. The psychometric properties of the questionnaire were studied in our sample population. RESULTS: The internal consistency of the HIP questionnaire was weak as Cronbach α coefficients of most of the domains were low. The study of the composite matrix resulted in the improvement of the internal consistency after the elimination of some items. Moreover, the "adapted domains" were created by reverse-scoring items with positive implications.The composite reliability and the average variance extracted of all the domains were analyzed. Analysis of discriminate validity through heterotrait-monotrait ratio of correlation ratio analyses of corresponding Hospital Anxiety and Depression Scale domains was also performed along with reliability analysis. There results were satisfying for the adapted domains. CONCLUSIONS: The adapted domains of the 27 items questionnaire with reverse scoring of 8 items presented with good psychometric properties, allowing their use in clinical trials and in clinical practice.

Does Social and Religious Background Matter? A Study of the Psychosocial Impact of Human Papillomavirus on Lebanese Women.

OBJECTIVE: The human papillomavirus (HPV) has been associated with an important psychosocial impact. This impact has been poorly evaluated in developing countries, mostly because of the lack of instruments to quantify it. The HIP questionnaire aims to measure HPV-associated affective burden. Our team has previously translated this questionnaire to Arabic and used it to assess the impact of HPV on Lebanese women. MATERIALS AND METHODS: While the HIP is a specific tool to evaluate the emotional impact of HPV, the Hospital Anxiety and Depression Scale questionnaire consists of 2 scales, anxiety and depression, and assess the psychological distress in nonpsychiatric patients. The HPV impact profile and Hospital Anxiety and Depression Scale questionnaires were administered to 118 Lebanese women with an HPV-related presentation, aiming to determine which aspect of these women's lives was mostly affected. The association with different sociodemographic factors was also assessed. RESULTS: Feelings of "concerns and worries" were mostly strongly felt in our population except for women with genital warts who were more concerned with the risk of transmission and the impact on their partners. All women had predominant feelings of anxiety.Religion was a statistically significant influencing factor and employment a protective factor. Muslim women demonstrated significant adverse affects on HPV impact profile domains that included: "sexual impact," "self-image," "interaction with doctors," and "health control/life impact." CONCLUSIONS: Different women perceive the diagnosis of HPV and HPV-related lesions differently. In this study, employment was found to play a protective role, but the biggest influencers were social and religious beliefs.

Oncoplastic breast-conservative surgery for breast cancers: a uni-institutional case-control study.

The current study was designed to compare oncological outcomes between oncoplastic (OBCS) and conventional breast-conserving surgery (BCS). Data collected retrospectively from two groups of patients diagnosed with breast cancer, cases group (OBCS) and control group (BCS), were analyzed. A total of 277 women were included in the analysis: 193 (69.7%) in the cases group and 84 (30.3%) in the control group. Resected volume was larger in the OBCS group (438.05 ± 302.26 cm3 vs 223.34 ± 161.75 cm3; p < 0.001). Re-excision was required for 7.1% of patients receiving BCS versus 4.7% in the OBCS group (p = 0.402). After long-term follow up, no local recurrences occurred in the OBCS group, while 2.4% of patients receiving BCS had local relapse (p = 0.045). Compared with BCS, OBCS increases oncological safety in terms of re-excision rate and local recurrence.

Predictive factors of lymph node metastasis and pattern of repartition in patients with epithelial ovarian cancer.

Aim: To determine the rate, repartition and risk factors of lymph node (LN) metastasis in patients with epithelial ovarian cancer. Methods: We reviewed retrospectively the pathological and clinical data of 184 patients with epithelial ovarian cancer at a tertiary care center in Beirut, Lebanon. Results: 88% of patients received a pelvic and para-aortic lymphadenectomy. 70% of patients presented LN metastases at both pelvic and para-aortic levels, while isolated pelvic or para-aortic LN metastases were seen in 16 and 14% of cases, respectively. In a univariate analysis, the rate of positive LNs was higher in patients with serous histology (65 vs 33%; p < 0.001), high-grade tumors (68 vs 26%; p < 0.001), bilateral adnexal involvement (74 vs 27%; p < 0.001), advanced clinical stage (p < 0.001), interval debulking surgery (63.2 vs 36.8%; p = 0.003) and positive peritoneal cytology (79 vs 26%; p < 0.001). In a multivariate analysis, the rate of LN involvement was significantly higher in patients with higher grade, advanced clinical stage and positive peritoneal cytology. Conclusion: Serous histology, grade 3 tumors, positive peritoneal cytology, advanced clinical stage, interval surgery and bilateral adnexal involvement can predict LN metastasis in patients with epithelial ovarian cancer.

Breast and tumor volumes on 3D-MRI and their impact on the performance of a breast conservative surgery (BCS).

Breast conservation rate is being increasingly used nowadays as a marker of breast cancer care among hospitals. Searching for the ideal technique to predict the feasibility of BCS is ongoing. For this matter, the preoperative MRIs of 169 patients operated with radical or conservative surgery were reviewed. We estimated the tumor volume (TV) and breast volume (BV) on enhanced 3D-MRI and compared the tumor-to-breast volume ratio (TV/BV) in both groups. The mean ratio was 9.5% in the mastectomy group and 1.7% in the BCS group. A tumor-to-breast volume ratio less than 4% seemed to favor the adoption of a conservative option. Our data suggest that preoperative 3D-MRI can orient the surgical approach by assessing the TV/BV ratio, increasing lumpectomy rates with clear margins and good cosmetic outcome.

Periductal stromal tumor of the breast in a young lady: A case report.

We present the case of a 30-year-old lady who underwent a core needle biopsy for a BIRADS 4 lesion of her left breast and was diagnosed as having a cellular fibroadenoma. The final diagnosis after excision returned to be a periductal stromal tumor (PST). An extremely rare entity, the PST is actually classified as a subtype of phyllodes tumor, with specific criteria that are only found upon histological examination of the specimen. Care should be taken when considering the diagnosis of fibroadenoma based only on clinical, radiological, and biopsy findings. Any nonclassical, clinical, or radiological findings should prompt a wide excision. Prognosis is generally good when clear margins are obtained and in the absence of malignant heterologous elements.

The use of hysteroscopic endometrectomy in the conservative treatment of early endometrial cancer and atypical hyperplasia in fertile women.

OBJECTIVE: To illustrate the effectiveness of hysteroscopic endometrial resection in conservative treatment of early endometrial cancer/atypical hyperplasia in women of reproductive age. METHODS: Review of outcomes of women of reproductive age who underwent fertility sparing treatment (hysteroscopic superficial endometrectomy followed by progestin therapy) in early endometrial cancer. RESULTS: Eight women with Stage I endometrial cancer and three with atypical endometrial hyperplasia underwent hysteroscopic superficial endometrial resection, followed by 1-year treatment with oral megestrol acetate. One patient had a synchronous endometrioid ovarian carcinoma. One patient with Grade 2 carcinoma opted for conservative treatment and had hysterectomy 3 months later for persisting disease. Ten patients showed no evidence of residual disease during a 12-month follow-up period with regular hysteroscopy. Five patients had seven pregnancies without assisted reproductive technology. One patient got pregnant after one attempt of in-vitro fertilization and oocyte donation. Pregnancy rate was 54.5%; two patients had two successful pregnancies and deliveries. Average time to pregnancy was 16 months from the end of treatment. All babies were delivered vaginally. CONCLUSION: Total superficial endometrial resection followed by progestin can be considered in patients with early endometrial cancer/atypical hyperplasia who still want to conceive. It does not seem to impair fertility nor pregnancy outcomes in women of reproductive age.

Radiology management of a 'breast unit' during COVID-19 pandemic: a single institution experience.

Aim: To describe the activity in the 'breast unit' at the department of radiology during the COVID-19 lockdown in a university hospital treating COVID-19 patients in a Middle-Eastern developing country. Materials: This was a retrospective study conducted from March 9 until 11 May 2020, in the breast unit at the department of radiology of a central university hospital in a Middle-Eastern developing country. Data were collected from 205 patients visiting the breast unit during the lockdown period and compared with the activity in the same period in the previous year. Results: Reduction of the breast unit activity was estimated at 73%. In addition, 153 mammograms, 205 ultrasounds, and 16 breast MRIs were done. Indications for mammogram were screening (41.5%), follow-up (22%), clinical symptoms (20%) and breast cancer surveillance (16.5%). MRI was performed mostly for preoperative surgical management. The rate of positive biopsies was 41%. All staff members and patients have accommodated to new adjustments. Conclusion: Activity in the breast unit dropped during the lockdown period. Staff should continue to seek their own and their patient's safety without diminishing the quality of healthcare.

"You only live twice": multidisciplinary management of catastrophic case in placenta Accreta Spectrum-a case report.

BACKGROUND: Placenta percreta is associated with high hemorrhagic risk and can be complicated with fatal thromboembolic events. Involving a multidisciplinary team in the treatment of these patients is mandatory to reduce morbidity and mortality. CASE PRESENTATION: This paper reports the case of a 22-year-old patient with placenta percreta who was referred to our tertiary care center for delivery. Few hours after undergoing a successful cesarean hysterectomy, the patient developed a pulmonary embolism and cardiac arrest. A transthoracic echocardiogram done in the intensive care unit (ICU) showed a thrombus in the right ventricle. After cardiac resuscitation, the patient underwent an urgent thoracotomy and a pulmonary artery thrombectomy; many clots were retrieved from the pulmonary artery. After weaning from extracorporeal circulation, an intraoperative transesophageal cardiac ultrasound enabled the medical team to detect a new free-floating thrombus in the right atrium and right ventricle, and consequently to perform an embolectomy and prevent the patient's death. CONCLUSION: This case emphasizes the role of multidisciplinary team in treating high-risk obstetric cases that could be complicated with massive and fatal thromboembolic events. The use of intraoperative transthoracic echocardiography helps in detecting a new thrombus and guides the anesthesiologist in the intra-operative monitoring.

MRI-based predictive factors of axillary lymph node status in breast cancer.

To evaluate the diagnostic value of diffusion-weighted imaging (DWI) in combination with conventional MRI in predicting metastatic axillary lymph nodes (ALN) in breast cancer (BC). We reviewed pathological findings and clinical breast MRI examinations of 169 patients with invasive BC who were evaluated at the Hôtel-Dieu de France Hospital in 2009-2015. Morphological parameters and apparent diffusion coefficient (ADC) value were compared with pathological nodal status. Independent t-test/chi-square test and a Pearson correlation analysis were used. With pathological diagnosis as reference, MRI-based interpretations were 87.5% specific and 70.3% sensitive. On conventional MRI, the round shape of lymph nodes (LNs), loss of fatty hilum, irregular margins and hypo-intensity/heterogeneous intensity on T2-weighted sequence were statistically significantly different between metastatic and nonmetastatic groups (P < .001, each). Mean size of metastatic ALN was larger compared with negative ALN (13.9 mm vs. 10.9 mm, P < .001). LNs ≥ 12 mm were associated with higher risk of metastasis (P < .001). ADC value was not significantly different between both groups (P = .862). Conventional MRI using the ALN shape, signal intensity in T2-weighted sequences, loss of fatty hilum, regularity of the margins and size of the LNs can evaluate the axilla with high specificity. ADC value could not be used as a reliable parameter.

Different TP53 mutants in p53 overexpressed epithelial ovarian carcinoma can be associated both with altered and unaltered glycolytic and apoptotic profiles.

BACKGROUND: p53 is a tumor suppressor and key regulator of glycolysis in cancer cells, however highly mutated in tumors. In ovarian cancer, studies concerning p53 mutations focus on the DNA binding domain since the majority of hotspot mutations affects this region. Yet, mutations in other regions such as the proline rich domain may also affect the protein's expression and activity. The aim of this study is to investigate the effect of various positions of mutations in TP53 gene on glycolysis, apoptosis and transcription of p53 target genes. METHODS: Mutations frequency and their effect on p53 expression were assessed by PCR-SSCP, sequencing and immunohistochemistry on 30 ovarian cancer biopsies. Six tumors were cultured, as well as SK-OV-3, OVCAR-3 and Igrov-1. SK-OV-3 cells were transfected with 2 TP53 mutants. p53 transcriptional activity was assayed by qPCR, apoptosis by flow cytometry and glycolysis by glucose and lactate measurements, with quantification of glycolytic enzymes expression. RESULTS: Our results showed a high frequency of the P72R mutant, associated with p53 overexpression in the ovarian biopsies. However, P72R mutant cells showed similar apoptosis and glycolysis as WT cells. DNA binding domain mutations decreased the transcriptional activity of the protein and increased glucose consumption and lactate production. CONCLUSION: Despite the overexpression of the P72R mutated protein in the biopsies, it showed a similar apoptotic activity and glucose regulation ability as WT p53. Knowing that p53 expression status is used for chemotherapeutic approaches and prognosis in ovarian cancer, the results obtained highlight the importance of locating TP53 mutations.

[Laparoscopic treatment of vaginal agenesis: three cases]. / Traitement coelioscopique de l'agénésie vaginale: trois études de cas.

BACKGROUND: Ninety per cent of cases of congenital vaginal agenesis are represented by the Mayer-Rokitansky-Küster-Hauser syndrome, the remaining 10% being represented by the testicular feminization syndrome and vaginal aplasia. Numerous surgical methods for the treatment of vaginal agenesis have been described. Neovagina construction by sigmoid colpoplasty seems to be the best surgical option as regards the anatomical and functional outcome. METHOD: We report the case of three patients operated of neovagina construction with a sigmoid graft by a laparoscopic-perineal approach. RESULTS: The surgical intervention lasted for 330 minutes, 210 minutes and 150 minutes respectively for the three patients. There were no perioperative complications. The duration of hospitalization was respectively 7, 4 and 6 days. The length of the neovagina was 15, 14 and 18 cm without retraction on the follow-up at 2 and 6 months. The vaginal wall maintained its patency allowing normal intercourse. The patients had normal sexual life after the surgery. CONCLUSION: Our results demonstrate the feasibility of laparoscopic-perineal neovagina construction by sigmoid colpoplasty when it is performed by experienced surgeons in gynecology and digestive laparoscopic surgery.

The Lebanese percreta group: A retrospective cohort study of both radical and conservative management outcomes of abnormally invasive placenta.

OBJECTIVE: The aim of the present study was to illustrate the outcomes of abnormally invasive placenta (AIP) cases managed in three leading centers in Lebanon. METHODS: We conducted a retrospective multicenter cohort study. Patients managed conservatively (cesarean delivery with successful placental separation) or radically (cesarean hysterectomy) were included in the study. Data included patient characteristics, surgical outcomes (blood loss, operative time, transfusion, partial bladder resection), maternal outcomes (death, length of stay, ICU admission, postoperative hemoglobin level) and neonatal outcomes (Apgar score, neonatal weight, admission to neonatal intensive care unit, neonatal death). RESULTS: The study included 189 patients. In the radical treatment subgroup (141/189), patients were para 3 and delivered at 34 4/7 weeks in average, bled 1.5 L and were transfused with three packed red blood cells, with operative time averaging 160 min. A total of 36% were admitted to the ICU and patients stayed on average for 1 week despite partial bladder resection in 19% of cases. Unscheduled radical delivery occurred at a lower gestational age, was associated with more blood loss, higher rate and volume of transfusion, and risk of maternal and neonatal death. In addition, patients delivered in an unscheduled fashion experienced higher rates of partial bladder resection and longer interventions. In the conservative treatment subgroup, on average patients were para 2 and delivered at 36 weeks, bled 800 mL on average with low rates of transfusion (35%) and ICU admission (22.9%). With regard to neonatal outcomes, the average neonatal birth weight was 2.4 kg in the radical subgroup and 2.5 kg in the conservative subgroup. Neonatal death occurred in 5.4% of cases requiring radical management while it occurred in 2% of patients treated conservatively. CONCLUSION: Through their multidisciplinary approach, the three centers demonstrated that management of AIP in Lebanon has led to excellent outcomes with no maternal mortality occurring in scheduled radical treatment. By comparison of the three leading centers, pitfalls in each center were identified and addressed.

HSP27 modulates tumoural immune evasion by enhancing STAT3-mediated upregulation of PD-L1 and NLRC5 in ovarian cancer.

Multiple preclinical studies have demonstrated that the addition of hyperthermia (HT) to immunotherapy could enhance tumour immunogenicity and stimulate an antitumour immune response, primarily via heat shock proteins (HSPs). However, antitumour immune responses are often impeded by immune evasion mechanisms, such as the overexpression of programmed death-ligand1 (PD-L1) and the loss of major histocompatibility complex class 1 (MHC-1) expression. In this context, we sought to investigate the effect of HT on PD-L1 and NOD-like receptor family CARD domain containing 5 (NLRC5) identified as the key transcriptional activator of MHC-1 genes, and their interaction in ovarian cancer. A coculture of ovarian cancer cell lines (IGROV1 and SKOV3) with peripheral blood mononuclear cells was set up. Then, culture media conditioned with IGROV1 or SKOV3 subjected to HT was tested on untreated cell cultures. Knocking down heat shock protein B1 (HSPB1 or HSP27), heat shock protein A1 (HSPA1 or HSP70), and pharmacological inhibition of STAT3 phosphorylation were performed. Subsequently, we measured expression levels of PD-L1, NLRC5, and proinflammatory cytokines. The correlation between PD-L1 and NLRC5 expression in ovarian cancer was evaluated using the Cancer Genome Atlas database. We found that HT produces a concomitant decrease in PD-L1 and NLRC5 expression in coculture. Notably, however, the conditioned media by heat-shocked cells increases their expression. HSP27 knockdown can reverse this increase. Adding STAT3 phosphorylation inhibitor significantly enhanced the expression inhibition of PD-L1 and NLRC5 induced by HSP27 silencing. Correlation analysis showed a positive correlation in ovarian cancer between NLRC5 and PD-L1. These findings demonstrate that HSP27 modulates PD-L1 and NLRC5 expression through the activation of a common regulator 'STAT3'. Moreover, the positive correlation between PD-L1 and NLRC5 led us to conclude that the upregulation of PD-L1 and the downregulation of MHC class I are two mutually exclusive mechanisms of immune evasion in ovarian cancer.

Genetic profile of borderline ovarian tumors in the Lebanese population by whole-exome sequencing.

OBJECTIVE: To assess the molecular profile of borderline ovarian tumors (BOT) in the Lebanese population by whole-exome sequencing and to correlate the results with the patients' clinical profiles. METHODS: We included in this retrospective study 33 tumors belonging to 32 Lebanese women presenting with BOT, diagnosed at Hôtel Dieu de France. A total of 234 genes involved in different germinal and somatic types of cancer were analyzed using next-generation sequencing. RESULTS: Molecular analysis of these tumors allowed us to detect mutations in genes involved in the mitogen-activated protein kinase cascade in 57.58% of BOT and to identify variants affecting the DNA repair mechanism in 63.89% of samples. Furthermore, our initial analysis revealed an association between defects in DNA double-strand break repair and the occurrence of mucinous BOT, in 75% of the cases. CONCLUSION: This study reports the molecular profiles of BOT in the Lebanese population and compares them to the literature. This is the first study associating the DNA repair pathway to BOT.