Serous Carcinoma Of Fallopian Tube Research Articles

Case report: High grade serous fallopian tube carcinoma with rare NRG1 gene fusion presenting as widespread peritoneal carcinomatosis

The discovery of gene fusions involving Neuregulin-1 (NRG1) within solid tumors has important therapeutic implications, as they are being actively explored as targets for emerging ERBB/ERBB2/ERBB3-directed anti-cancer agents. NRG1 fusions are very uncommon across all tumor types and are infrequently documented in the medical literature. We report a female patient presenting with widespread peritoneal carcinomatosis diagnosed as high grade serous fallopian tube carcinoma, which harbored a previously undescribed MYH10::NRG1 fusion. Moreover, we queried the whole transcriptome sequencing results of neoplasms analyzed by a commercial laboratory (Caris Life Sciences) to determine the overall incidence of NRG1 fusions in carcinomas of the ovary, fallopian tube, and peritoneum (0.18%). Twenty-five additional tumors were found to demonstrate NRG1 fusions, including 20 new genes partners that had not been previously identified in gynecologic carcinomas. Overall, NRG1 fusion events are rare in ovarian, fallopian tube, and primary peritoneal carcinomas, but they may carry diagnostic significance in the context of borderline/low grade serous tumors, which demonstrated exclusively CLU::NRG1 fusions, and could have important predictive implications for response to ERBB/ERBB2/ERBB3-directed therapies.

Unusual Pattern of Spread of High-Grade Serous Fallopian Tubal Carcinoma in a Woman with BRCA1 Gene Mutation

A 40-year-old woman presented with chronic watery vaginal discharge for one-month and right pelvic pain radiating to the right flank for 2 weeks. Physical and pelvic examination revealed a right pelvic mass. Computerized tomography and magnetic resonance of whole abdomen revealed a 6-cm of heterogeneous mass at the right adnexa and a larger mass of 8-cm with internal cystic portions compressing on the inferior vena cava. Her serum cancer antigen (CA) 125 elevated to 540 U/ml. Surgical intervention revealed a right fallopian tube mass with an intact serosal surface, several enlarged pelvic and para-aortic nodes, and a bulky precaval node. No gross peritoneal nor other organ invasion was found. Complete surgical staging was performed by gynecologic oncologists and a surgeon, resulting in optimal surgery. Pathology revealed high-grade serous carcinoma of the right fallopian tube with metastasis to all resected nodes and a positive peritoneal cytology. Subsequent blood testing showed BReast CAncer (BRCA) 1 gene mutation. Adjuvant therapy with paclitaxel/carboplatin/bevacizumab was given for six cycles. Maintenance therapy with bevacizumab/olaparib, and periodic surveillance for other cancers, including breast magnetic resonance imaging were planned. This case presented an unusual pattern fallopian tubal cancer spread to a large precaval lymph node which was bulkier than the primary tumor. A thorough pre-operative evaluation and a surgical team specialized in cancer surgery are crucial for successful surgical management. Appropriate adjuvant treatment and follow-up for a woman with BRCA mutation were also to be emphasized.

Primary ovarian cancer combined with primary fallopian tube cancer: A case report

BACKGROUND Low grade serous carcinoma of the ovary (LGSOC) is a rare type of epithelial ovarian cancer with a low incidence rate. The origin of ovarian cancer has always been a hot topic in gynecological oncology research, and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes. Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system. There are only a few reports in the literature, but the mortality rate is very high. But in clinical practice, fallopian tube cancer is very common, but in most cases, it is classified as ovarian cancer. CASE SUMMARY We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment. The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube. No special treatment was performed after the surgery, and the patient was instructed to undergo regular follow-up without any signs of disease progression. CONCLUSION The prognosis of LGSOC is relatively good, over 80% of patients still experience disease recurrence.

Hereditary breast and ovarian cancer triggered by occult fallopian tube cancer: a case report

BackgroundAt the time of benign gynecological surgery, a prophylactic salpingo-oophorectomy or salpingectomy is increasingly being performed concurrently to reduce the risk of future ovarian and fallopian tube cancer. We herein describe a case of hereditary breast and ovarian cancer syndrome in which a hysterectomy and bilateral adnexectomy were performed with a preoperative diagnosis of benign tumor. A detailed pathological examination revealed occult fallopian tube cancer, and additional staging surgery provided an accurate pathology diagnosis.Case presentationA 72-year-old Japanese woman with a past history of breast cancer underwent a hysterectomy and bilateral oophoro-salpingectomy for the preoperative diagnosis of uterine myoma and a right para-ovarian cyst. In the detailed pathological examination, high-grade serous carcinoma of the right fallopian tube was detected incidentally, and a subsequent staging laparotomy confirmed single para-aortic lymph node metastasis. Furthermore, a mutation in germline BRCA2 was detected postoperatively, and the patient was finally diagnosed with hereditary breast and ovarian cancer syndrome. She was diagnosed with fallopian tube cancer International Federation of Gynecology and Obstetrics Stage IIIA1(i) and started on adjuvant therapy (six courses of paclitaxel and carboplatin followed by maintenance therapy with olaparib), and 18 months after surgery, she was free of disease.ConclusionThis is a case of fallopian tube cancer that was diagnosed incidentally and then accurately staged with additional advanced staging surgery. Even in the absence of grossly malignant findings, a detailed pathological search of the fallopian tubes and accurate staging surgery are important to make the necessary treatment decisions for the patient.

Clinical and genetic findings of incidental serous tubal intraepithelial carcinoma (145)

<b>Objectives:</b> Serous tubal intraepithelial carcinoma (STIC) is thought to represent the precursor lesion to the high-grade serous fallopian tube or ovarian carcinoma. STIC lesions are found 0.6-6% of the time in women undergoing risk-reducing salpingo-oophorectomy (RRSO) in the setting of a known hereditary predisposition. = However, due to the rarity of incidentally identified STIC lesions, there is limited data to guide management. NCCN guidelines suggest consideration of surgical staging and referral for genetic evaluation. In the absence of a known pathogenic variant as the indication for surgery, there is no data on rates of genetic testing or long-term outcomes. The objective of this study was to describe both clinical outcomes as well as genetic information collected for patients with incidentally noted STIC lesions. <b>Methods:</b> Following IRB approval, pathology records were used to identify all patients diagnosed with a STIC lesion on final pathology from 2007-2021 at a single institution. STIC lesions were characterized utilizing immunohistochemistry. Only patients with STIC lesions undergoing surgery for benign indications were included. Demographic, clinical-pathologic, and genetic data were collected. <b>Results:</b> A total of 16 patients were identified. The median age at diagnosis was 65.5 years (39-80). Fifteen patients (93.8%) had unilateral STIC lesions with one patient having bilateral STIC lesions. Most lesions were positive for p53 (94.1%) and had increased Ki67 proliferation, defined as >10% (94.1%). Two patients (12.5%) had a personal history of malignancy prior to their STIC lesion diagnosis. Patients had a wide variety of presentations, including pelvic mass (37.5%), prolapse (31.3%), abnormal uterine bleeding (25%), and pelvic pain (6.3%). Nine patients had additional surgical procedures performed (56.3%), and no cancer diagnosis was identified for any patient. Additional procedures included contralateral salpingo-oophorectomy, omentectomy, pelvic and paraaortic lymph node dissection, and peritoneal biopsies. No patients received adjuvant treatment. Eleven patients were offered a genetic counseling referral (68.8%), with seven patients completing a counseling appointment (63.6%). Five of the seven patients who completed their visit met criteria for testing based on additional personal and/or family history (71.4%), with one patient testing positive for a PALB2 pathogenic variant (20% of tested patients). Three patients, none of whom underwent genetic testing, were subsequently diagnosed with breast cancer during the follow-up period. <b>Conclusions:</b> Incidental STIC lesions are rare. In this cohort, there were no ovarian, fallopian tube, or primary peritoneal cancer diagnoses after additional surgical staging or during follow-up. More data is needed to guide treatment recommendations. However, compared to STIC lesions in patients undergoing RRSO for a known predisposition, it is not clear whether additional surgical procedures are warranted in patients with incidentally noted STIC lesions. Our data support NCCN recommendations for referral for genetic evaluation as 71% qualified for testing. One patient (20% of those who qualified for testing) had a clinically actionable pathogenic variant. Notably, three patients later developed breast cancer; however, without genetic testing, we cannot determine if there may be a genetic link. Further studies of these lesions are warranted.

The impact of neoadjuvant chemotherapy on the tumor microenvironment in advanced high-grade serous carcinoma

High-grade serous ovarian, fallopian tube or peritoneal carcinoma is an aggressive subtype of ovarian cancer that frequently develops resistance to chemotherapy. It remains contested whether the resistance is caused by the acquisition of novel molecular aberrations or alternatively through the selection of rare pre-existing tumor clones. To address this question, we applied single-cell RNA sequencing to depict the tumor landscape of 6 samples from a single case of advanced high-grade serous fallopian tube carcinoma during neoadjuvant chemotherapy (NACT). We analyzed a total of 32,079 single cells, with 17,249 cells derived from the pre-NACT multisite tumor tissue samples and 14,830 cells derived from the post-NACT multisite tumor tissue samples. We identified the diverse properties of the tumor, immune and stromal cell types between the pre-NACT and post-NACT tumors. The malignant epithelial cells displayed a high degree of intratumor heterogeneity in response to NACT. We showed that the primary resistant clone (clone 63) epithelial genotype was already present in the pre-NACT tumors, and was adaptively enriched after NACT. This clone 63 was correlated with a poor clinical prognosis. Furthermore, single-cell analysis of CD4+ T cells demonstrated that IL2RAhi-CCL22+-Tregs were selectively enriched in post-NACT tumors. Interestingly, this Treg subtype could recruit and enrich themselves through secreting the CCL22-CCR1 combination in pre-NACT and post-NACT tumors, and further express CD274 to suppress other CD4 and CD8 T cells through a CD274-PDCD1 axis in the post-NACT tumors, and this predicted an immunosuppressive state after NACT. Overall, our results provide important evidence for the adaptive resistance theory of HGSC, and for the potential development of therapeutic strategies to treat HGSC and improve the survival of patients with HGSC.

Primary High-grade Serous Carcinoma of the Fallopian Tube as an Incidental Intraoperative Finding: A Case Report

: Primary carcinoma of the fallopian tube is a rare, but fatal gynecologic cancer. The preoperative diagnosis of this carcinoma is challenging due to the absence of specific symptoms and signs, and in most patients, it is an intraoperative finding. A 55-year-old patient (G3Ab1P2) was referred to the urogynecology clinic of our hospital with the chief complaints of heavy, prolonged menstrual bleeding and a persistently abnormal yellow discharge, which could not be distinguished by the patient from urinary leaks. After a complete diagnostic work-up, the patient was identified as a candidate for hysterectomy due to abnormal vaginal bleeding resistant to megestrol acetate, family history of malignancy, and abnormal vaginal discharge. Laparotomy revealed unusual left fallopian tube features (large, bulky, and vegetative), suggesting malignancy. The intraoperative frozen-section analysis of the left fallopian tube and the ovarian specimens indicated the mass as a high-grade serous carcinoma of the fallopian tube. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy were performed for the patient. The definitive histopathological diagnosis was high-grade serous carcinoma of the left fallopian tube (stage 2b) with omental involvement, without any evidence of lymphovascular invasion. High-grade serous carcinoma of the fallopian tube is likely to have non-specific symptoms, causing a significant delay in diagnosis and treatment, which negatively affects the prognosis and survival of these patients.

Recurrent Serous Carcinoma of the Right Fallopian Tube Involving the Dome &#x0D; of Cecum and Rectum

Cancer of the fallopian tube is a rare and difficult condition to be treated. It is often clinically simulated by ovarian epithelial cancer or primary ovarian and peritoneal carcinomas. Most of relapses in these tumors are observed in the small pelvis. Extrapelvic relapses and metastases to other organs are rather uncommon. Surgical cytoreduction and platinum-based chemotherapy are the mainstay of treatment.The authors present a rare and noteworthy clinical case of recurrence of high-grade serous carcinoma of the right fallopian tube involving the caecum dome and rectum in a 65-year-old female patient. There was demonstrated the choice of surgical treatment tactics in this clinical case that allowed obtaining a 62-month survival result.

Bulky peritoneal carcinosarcoma with tiny high-grade serous carcinoma of the fallopian tube: a case report.

Peritoneal carcinosarcoma is a highly aggressive and uncommon neoplasm that has carcinomatous and sarcomatous components; the malignancy rarely localizes to the omentum. We report a case of a bulky peritoneal carcinosarcoma with tiny high-grade serous carcinoma of the fallopian tube. A 60-year-old female with a huge pelvic mass (12cm in diameter) underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy for tumor debulking. Pathological findings showed minimally invasive high-grade serous carcinoma of the left fallopian tube and carcinosarcoma of the omentum. Similar p53 diffuse immunostaining in the omental carcinosarcoma and the tubal carcinoma provides evidence for a clonal relationship between the two neoplasias. This case suggests a small serous carcinoma, originating in the tubal mucosa, subsequently became implanted in the omentum and grew preferentially, converting to a carcinosarcoma at a remote site.

High grade mucosal serous carcinoma of fallopian tube and serous tubal intraepithelial carcinoma (STIC) coexistent with ectopic tubal gestation

High-grade serous tubal intraepithelial carcinomas (STICs) are noninvasive carcinomas of the fallopian tube that have been found with varying frequency in tubectomy specimens. Serous tubal intraepithelial carcinoma is a precursor lesion for high-grade serous ovarian and peritoneal carcinoma. The incidence of STIC is estimated to occur in 0.6% to 6% of women who are BRCA positive or have a strong family history of breast or ovarian carcinoma. Immunohistochemical staining demonstrates aberrant p53 protein [removed]either diffuse nuclear over expression or complete absence of staining) and an increased Ki-67 proliferation index. We are describing rare incidental occurrence of high grade mucosal serous carcinoma of the fallopian tube with STIC in a patient undergoing tubectomy for ectopic tubal gestation and relevant immunohistochemical study of the lesion. Much attention has been directed to the fallopian tubes as the origin of malignant epithelial ovarian tumors, and STIC is now considered to be the origin of high-grade serous ovarian cancer. To avoid overlooking early-stage fallopian tube cancer, surgery for benign disease should also be accompanied by a detailed histopathological examination of the fallopian tubes. Possible management options include observation with annual physical examination and CA-125 estimation, surgical staging, or empiric chemotherapy. However, due to the lack of consensus regarding management options, referral to a gynecologic oncologist recommended. Associated ectopic gestation is probably due to partial obstruction caused by mucosal serous carcinoma of fallopian tube. Close spatial relationship of two such lesions suggests that, in all probability intraluminal mucosal carcinoma was responsible for interference in free transportation of the fertilized ovum through the tube , possibly, by impaired contractile activity of myosalpinx and consequently caused the ectopic tubal pregnancy. Keywords: Serous tubal intraepithelial c

Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC)

Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC)

Retroperitoneal Lymph Nodes: Cytoreduction in a Patient with Ovarian Cancer

Video Objective This video will exemplify the techniques necessary to safely complete a difficult dissection and debulking procedure in the obturator fossa in a patient with high-grade serous fallopian tube carcinoma. Setting This patient is a 67-year-old who presented with a right sided complex adnexal mass and elevated CA-125 of 1300 with concern for malignancy. She was taken to the operating room for laparoscopic right salpingo-oophorectomy with possible hysterectomy and staging. The frozen section was consistent with high-grade serous fallopian tube carcinoma. A bulky retroperitoneal mass was found in the right obturator fossa and the patient underwent debulking procedure. Interventions The patient underwent total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, lymph node dissection, debulking and omentectomy. The bulky retroperitoneal mass was carefully removed using a combination of sharp and blunt dissection, with special care to avoid the nerves and vasculature of the obturator fossa. At the conclusion of the surgery, there was no further evidence of disease. Conclusion In order to properly treat and stage ovarian cancer, a complete staging and debulking procedure must be performed. This video emphasizes the importance of a thorough understanding of retroperitoneal pelvic anatomy and highlights the utilization of impeccable surgical technique to safely perform a pelvic side wall dissection and debulking in the presence of abnormal pathologic findings.

LBA3 - VELIA/GOG-3005: Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC)

LBA3 - VELIA/GOG-3005: Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC)

1013P - Incidental early occult ovarian cancer after risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers followed in a community public hospital

BackgroundCarriers of germline BRCA1/2 mutations are at high risk of developing ovarian, tubal or peritoneal cancer. Actually, risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only definite preventive strategy. The aim of this study is to characterize the clinical and pathological features of early occult malignancies incidentally diagnosed after a RRSO in carriers of BRCA1/2 mutations followed at a high risk familial cancer clinic in a community public hospital in NW Spain. MethodsData were prospectively collected from 95 consecutive BRCA-positive women diagnosed at our high risk familial cancer clinic from March 2014 to March 2017. ResultsAmong 95 BRCA1/2 carriers (median age 45 years) 38 women were healthy and 57 have had a previous breast cancer diagnosis. Half of the carriers hold the founder mutation R71G in BRCA1 (69 in BRCA1, 25 in BRCA2, and 1 was a carrier of a mutation in both genes). RRSO was performed in 29 cases (21 in BRCA1 and 8 in BRCA2; median age 50 years). Three BRCA1/2 carriers older than 45 years-old refused to undergo a RRSO. After RRSO two patients (6.4%), both BRCA1-positive, were found to have an early occult adnexal malignancy upon pathology study. One 64-year-old carrier had an invasive serous fallopian tube carcinoma stage I with no involvement of the ovaries plus a stage I endometrial endometrioid carcinoma on the staging hysterectomy. The second 44-year-old women were found at the time of the RRSO a stage Ia invasive high grade serous ovarian carcinoma with no fallopian tubes involvement. ConclusionsA 6.4% incidence of early occult adnexal malignancy after RRSO was found in our cohort of BRCA1/2 carriers. This incidence is similar to that previously published in studies done at international reference centers. The coordinated management of BRCA1/2 mutation carriers between different departments of our institution allows results comparable to international standards. Greater efforts must be made to improve the acceptance of RRSO by BRCA carriers, especially after the age of 40. Legal entity responsible for the studyAuthor: Begoña Graña Suárez. FundingHas not received any funding. DisclosureB. Grana Suarez: Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Servier. All other authors have declared no conflicts of interest.

Characterization of MicroRNA-200 pathway in ovarian cancer and serous intraepithelial carcinoma of fallopian tube

BackgroundOvarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors.MethodsRNA prepared from ovarian and fallopian tube epithelial and stromal fibroblasts was subjected to quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to determine the expression of miR-200 families, target and effector genes and analyzed for clinical association. The effects of exogenous miR-200 on marker expression in normal cells were determined by qRT-PCR and fluorescence imaging after transfection of miR-200 precursors.ResultsOvarian epithelial tumor cells showed concurrent up-regulation of miR-200, down-regulation of the four target genes (ZEB1, ZEB2, TGFβ1 and TGFβ2), and up-regulation of effector genes that were negatively regulated by the target genes. STIC tumor cells showed a similar trend of expression patterns, although the effects did not reach significance because of small sample sizes. Transfection of synthetic miR-200 precursors into normal ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells confirmed reduced expression of the target genes and elevated levels of the effector genes CDH1, CRB3 and EpCAM in both normal OSE and FTE cells. However, only FTE cells had a specific induction of CA125 after miR-200 precursor transfection.ConclusionsThe activation of the miR-200 pathway may be an early event that renders the OSE and FTE cells more susceptible to oncogenic mutations and histologic differentiation. As high-grade serous ovarian carcinomas (HGSOC) usually express high levels of CA125, the induction of CA125 expression in FTE cells by miR-200 precursor transfection is consistent with the notion that HGSOC has an origin in the distal fallopian tube.

Prognostic significance of Tspan9 in gastric cancer.

Tetraspanins are a large superfamily of glycoproteins, which are engaged in a wide range of specific molecular interactions by forming tetraspanin-enriched microdomains. Tetraspanin 9 (Tspan9) is a previously poorly studied tetraspanin gene, which was predominantly identified as an amplified gene in serous Fallopian tube carcinoma. However, the expression and role of Tspan9 in gastric cancer have yet to be fully elucidated. The aim of the present study was to evaluate the expression and clinical significance of Tspan9 in gastric cancer. In the present study, 105 gastric cancer tissue samples and corresponding adjacent normal samples were detected for Tspan9 expression using immunohistochemistry; furthermore, the association between clinical characteristics and Tspan9 expression was also analyzed. Tspan9 expression was determined to be significantly lower in cancer samples compared with those in corresponding adjacent normal samples (P<0.001). However, its increased levels of expression in cancer samples appeared to demonstrate a poorer prognostic tendency, which is associated with deeper tumor depth (P=0.025), more nodal involvement (P=0.01), more advanced tumor/lymph node/metastasis (TNM) stages (P=0.017) and a larger tumor size (P=0.026). Additionally, multivariate analysis demonstrated that high expression of Tspan9 was an independent prognostic factor for poor overall survival (P<0.01). These results suggested that Tspan9 may be used as a potential prognostic factor in gastric cancer.

High-grade serous carcinoma of ovary and fallopian tube after the new protocol of assignment of primary site: An analysis of incidence, demographics, and clinical features

High-grade serous carcinoma of ovary and fallopian tube after the new protocol of assignment of primary site: An analysis of incidence, demographics, and clinical features

Abstract A07: Homologous recombination mutations and overall survival in high-grade serous, endometrioid, and clear cell ovarian carcinomas.

Abstract Background: Defects in homologous recombination (HR) DNA repair are common in high grade serous ovarian, peritoneal and fallopian tube carcinoma (HGSOC). Other than mutations in BRCA1 and BRCA2 (BRCA1/2), the molecular causes of HR deficiency have not been well delineated. The frequency of HR deficiency in non-serous ovarian carcinoma is not known. We previously identified that germline and somatic HR mutations in 13 genes in OC was associated with improved survival. We sought to replicate these data in an independent tumor set, while sequencing a larger number of DNA repair genes. Methods: We used BROCA-HR to sequence 65 DNA repair genes in germline (blood) and tumor DNA from 363 women with ovarian (262), peritoneal (91), or fallopian tube (10) carcinoma from an institutional tissue bank. Cox proportional hazards models, adjusted for stage and residual tumor after cytoreduction, were used to assess associations between mutations in DNA repair genes in HR or related pathways and overall survival from diagnosis. Results: In total, 96/363 (25%) patients had 59 germline and 45 somatic deleterious mutations in HR genes, including 34 germline and 22 somatic BRCA1/2 mutations. Damaging mutations found in other HR genes included 25 germline and 23 somatic in the following genes: 5 ATM, 6 ATR, 1 BAP1, 2 BARD1, 6 BLM, 2 BRIP1, 2 BRE, 1 BRCC3, 2 CHEK2, 1 ERCC1, 1 FANCG, 1 FANCI, 2 FANCL, 8 FANCM, 1 NBN, 2 PALB2, 1 RAD51D, 1 RBBP8, 1 SLX4, 1 UIMC1 and 1 XRCC2. Of 322 HGSOC, HR mutations occurred in 86 patients (26.7%) including 54 (16.8%) germline and 32 somatic (9.9%). HR mutation rates were similar across the different non-serous histologies. Of 13 clear cell OC, 2 (15.3%) had germline mutations in non-BRCA1/2 HR genes and 3 (23.1%) had PTEN/PIK3CA mutations. Of 27 endometrioid OC, 3 (11.1%) had HR mutations (1 germline BRCA1, and 2 non-BRCA1/2 somatic HR mutations). PTEN/PIK3CA mutations were identified in 9 (2.8%) HGSOC, 3 (23.1%) clear cell and 2 (7.5%) endometrioid. HR mutations demonstrated a trend towards improved long-term overall survival (hazard ratio = 0.78, 96% CI 0.57-1.05) after accounting for stage and debulking status. Conclusions: These data not only indicate that damaging HR mutations, both germline and somatic, are found in endometrioid and clear cell as well as HGSOC, but also confirm our previous results showing an association between HR mutations and improved overall survival in OC. We are now sequencing 163 additional non-serous OC to augment the current analysis and these data will be available at presentation. Citation Format: Maria I. Harrell, Matthew J. Maurer, Ethan P. Heinzen, Ming K. Lee, Kimberly R. Kalli, Kathy J. Agnew, Ann L. Oberg, Tom Walsh, Barbara M. Norquist, Lynn C. Hartmann, Scott H. Kaufmann, Elizabeth M. Swisher. Homologous recombination mutations and overall survival in high-grade serous, endometrioid, and clear cell ovarian carcinomas. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A07.

Robotic resection of bulky aorto-caval lymphadenopathy in a patient with serous fallopian tube carcinoma

Objective:Inpatientswithovarian/fallopiantube/primary peritoneal cancer, maximum surgical effort is aimed at complete cytoreduction as it results in longer overall survival [1]. In selected patients, achieving this goal with robotic-assisted surgery provides the patient with the benefits of minimally invasive surgery [2,3]. The authors present resection of bulky aorto-caval lymph nodes in a patient with serous fallopian tube cancer. Methods: A 51-year-old underwent robotic hysterectomy and bilateral salpingo-oopherectomy by her gynecologist for bilateral complex adnexal masses and leiomyomatous uterus. The findings were consistent with a high-grade serous carcinomaarising from the right fallopian tube. The tumor size was 7 × 1.7 cm and was metastatic to bilateral ovaries. Pelvic washings and lymphovascular invasion were negative. After the patient was referred to gynecologic oncology with these findings, enhanced computed tomography demonstrated 4.5 × 2 cm lymphadenopathy at the level of aortic bifurcation and 2.5 × 2 cm

Invasion patterns of metastatic high-grade serous carcinoma of ovary or fallopian tube associated with BRCA deficiency

High-grade serous carcinomas of the uterine adnexa with BRCA1 deficiency (high-grade serous carcinomas-BRCA) have recently been described to demonstrate characteristic histopathological features. We hypothesize that metastatic high-grade serous carcinomas-BRCA cases exhibit characteristic morphological features as well. We studied 102 high-grade serous carcinomas with known BRCA1 and BRCA2 genotype from the archives of the Department of Pathology at Memorial Sloan-Kettering Cancer Center. The primary site morphological characteristics of these cases were reported previously; we now focus solely on tumor morphology in sites other than the uterine adnexa (ie, metastatic sites). The study group consisted of the following case types: 13 BRCA1 germline mutations; 5 BRCA1 somatic mutations; 10 BRCA1 promoter methylation; 4 BRCA2 germline mutations; 1 BRCA2 somatic mutation; 11 lacking BRCA1 or BRCA2 abnormality; 58 cases lacking BRCA1 or BRCA2 germline mutation. Two observers independently scored invasion patterns and microscopic tumor architecture while blinded to genotype. Concordance between observers and correlations between metastatic patterns and the following indices were studied: genotype, primary site tumor characteristics, and BRCA1 immunohistochemistry. Concordance between observers was excellent (κ values >0.9). All cases with BRCA1 or 2 abnormalities showed either pushing pattern metastases (76%) or infiltrative metastases composed only of micropapillae (24%). In contrast, all cases lacking BRCA1 or 2 abnormalities showed infiltrative metastases that contained combinations of papillary, glandular, and, rarely, cribriform and micropapillary architecture (P<0.0001 for comparison with pushing metastasis and P<0.001 for comparison with purely micropapillary architecture). Morphological assessment of metastatic carcinomas, a highly reproducible exercise, accurately correlated with BRCA1 status in every case, unlike morphological assessment of primary site adnexal high-grade serous carcinomas or BRCA1 immunohistochemistry. Metastatic high-grade serous carcinomas-BRCAs exhibit characteristic morphological features that appear more sensitive and specific for BRCA mutations than two other morphologically based prediction systems and should be easier to apply in practice. These findings should be validated prospectively in an independent cohort.