Serous Carcinoma Of Fallopian Tube Research Articles

Risk-Reducing Salpingo-Oophorectomy (RRSO) in BRCA Mutation Carriers

Women carriers of BRCA mutations often have occult malignancy found at the time of risk-reducing bilateral salpingo-oophorectomy (RRSO). We report outcomes in 111 consecutive BRCA-positive women who had RRSO using a rigorous surgical-pathological protocol from 1996 to 2008. We identified risk factors associated with finding an occult malignancy at RRSO with outcomes followed for a median of 61 months. A total of 111 BRCA carriers elected RRSO, 10 patients [9.1%] had 14 sites of occult neoplasia. Two patients had invasive serous fallopian tube carcinoma (TSC) only, 1 patient had invasive serous ovarian carcinoma (OSC) only, 5 patients had tubal intraepithelial carcinoma (TIC) only, and 2 patients had multifocal lesions of the ovary (OSC) and TIC. Occult ovarian carcinomas were only detected in BRCA1 patients, and all BRCA2 carcinomas involved only the fallopian tube. The odds of finding occult carcinoma is 4 times greater (odds ratio, 4.3; 95% confidence interval, 1.06-20.7) in women older than 50 than in younger ones (P=0.023). A history of invasive breast cancer was associated with a reduced risk of occult carcinoma (odds ratio, 0.2; 95% confidence interval, 0.05-0.85). In median follow-up of 5 years, recurrence rate after detection of an occult carcinoma was 10% and the risk for primary peritoneal carcinoma was less than 1%. A rigorous surgical protocol with meticulous pathologic review at RRSO yielded an overall detection rate of 9.1% for occult gynecological carcinoma in BRCA mutation carriers followed by a multidisciplinary team at a single institution. Primary peritoneal carcinoma after RRSO is rare.

An orthotopic model of fallopian tube serous carcinoma.

e15511 Background: Recent studies suggest that some high grade serous tumors of the pelvis, including a subset of ovarian serous carcinomas, originate from the fallopian tube (FT). These serous tumors typically harbor p53 mutations. Our goal was to develop an orthotopic model of metastatic FT carcinoma with characteristic features of serous pelvic tumors. Methods: After Institutional Review Board and Animal Care and Use Committee approvals, written informed consent was obtained from a patient with suspected metastatic pelvic carcinoma. At the time of surgery, non-necrotic tumors were transplanted via intraperitoneal (IP) injection into immunocompromised mice (passage, P1). Tumors were grown, harvested and re-implanted into a second cohort of mice (P2). Finally, tumors were passaged to a larger cohort (P3). P3 mice were treated with saline (n= 8) or cisplatin, 5mg/kg (n=8), weekly for 4 weeks. After sacrifice, tumors from each passage and treatment group were excised and frozen or paraffin-embedded. Patient information was obtained from the medical record. Results: The patient underwent optimal cytoreductive surgery for metastatic serous FT carcinoma in the presence of serous tubal intraepithelial carcinoma (STIC). The FT cancer, areas of STIC and a focus of normal FT, stained positive for p53 and mib-1. The patient was in remission after 6 months of taxane/platinum chemotherapy. IP tumor propagation was readily achieved up to P3 in the mice. Similar to the patient, orthotopic tumors were identified along peritoneal and mesenteric surfaces and confirmed by hematoxylin and eosin staining, p53 and mib-1. Cisplatin-treated mice had fewer tumor implants and fewer mib-1 stained cells compared to controls (p<0.05). Conclusions: Successful in vivo propagation of an orthotopic model of pelvic serous carcinoma arising from an identifiable precursor FT lesion was achieved. Histological characteristics of the patient’s metastatic FT cancer were maintained through P3 and the response to cisplatin in the mice reflected the patient’s response to therapy. This model is currently being used as a tool to study novel therapies for the treatment of p53 signature, serous carcinomas of the pelvis.

Serous Fallopian Tube Carcinoma: A Retrospective, Multi-Institutional Case-Control Comparison to Serous Adenocarcinoma of the Ovary

Primary carcinoma of the fallopian tube (PCFT) accounts for perhaps 1% of genital tract cancers. The investigators undertook a matched, case-control comparison of 96 women with a diagnosis of PCFT and 189 control women having ovarian carcinoma (OC). The groups were matched for age, tumor stage, and the presence of residual disease. All patients were surgically staged and, if indicated, given platinum-based chemotherapy. Fifty early-stage (FIGO stage I or II) cases of PCFT were matched with 97 OC patients. A regimen of carboplatinum and paclitaxel was used in more than 80% of cases. Median follow-up intervals for the PCFT and OC groups were 57 and 42 months, respectively. The respective 5-year overall survival rates were 95% and 76%. Excluding cases of stage IA PCFT, the 5-year survival rate was 92% for patients with PCFT and 70% for those with OC. Progression-free 5-year survival rates were 62% and 50%, respectively, not a significant difference. Excluding early-stage PCFT cases that were found incidentally during surgery for benign conditions or at the time of salpingo-oophorectomy, 5-year survival was 97% for PCFT cases and 77% for cases of OC. When 46 cases of stage III/IV PCFT were matched with 92 OC cases and followed up for nearly 3 years, the 3-year overall survival rate was 59% for both groups. Progression-free 3-year survival rates were 26% for PCFT patients and 21% for control patients with OC (P = 0.46). These findings should lead clinicians to be assured that treatment of PCFT should mirror that of OC.

Serous fallopian tube carcinoma: A retrospective, multi-institutional case–control comparison to serous adenocarcinoma of the ovary

Objective. Primary carcinoma of the fallopian tube (PCFT) is a rare malignancy comprising 1% of genital tract cancers. We sought to compare survival trends between PCFT and ovarian carcinoma (OC) patients (pts) in a matched, case–control comparison. Materials and methods. Patients with PCFT were identified from five academic centers. Two OC controls were identified for each PCFT pt based on age, stage, and residual disease. All pts were surgically staged and treated with platinum based chemotherapy (CT) if indicated. PFS and OS were then compared with Kaplan–Meier analysis. Results. 96 PCFT cases and 189 OC controls were identified. 50 early stage PCFT were matched with 97 OC pts. The most common CT regimen was carboplatinum and paclitaxel in 84 and 86% respectively. Median follow-up was 57 and 42 months for the PCFT and OC groups and 5-year overall survival (OS) differed at 95% and 76% ( p = 0.02). 46 Stage III/IV PCFT pts were matched with 92 OC controls. 88.5% were optimally debulked. Median follow-up was 33 and 35 months for PCFT and OC pts and 3-year overall survival was 59% for both groups. Conclusions. This is the first study to compare outcomes for PCFT and OC in a matched, case–control comparison. Our study demonstrates that, for advanced stage PCFT, a similar survival outcome is obtained compared to OC patients. This should reassure clinicians that treatment of PCFT should mirror that of OC and that PCFT should be included in clinical trials.

HER‐2/neu and p27Kip1 in progression of Fallopian tube carcinoma: an immunohistochemical and array comparative genomic hybridization study

To determine expression of p53, HER-2/neu and p27(Kip1) in serous Fallopian tube carcinoma (FTC) in relation to stage and grade, and to investigate DNA copy number changes of HER-2 and P27KIP1 as a potential mechanism of altered expression status. Immunohistochemistry was performed on 28 serous FTCs and 10 normal Fallopian tubes. p53 protein accumulated and p27(Kip1) was down-regulated significantly in early-stage FTCs compared with normal Fallopian tubes. HER-2/neu overexpression was absent in normal Fallopian tubes and in all stage I FTCs (n = 6) but present in 57% (12/21) of advanced-stage FTCs. No differences in expression between grade 2 and 3 tumours were detected. HER-2 gain/amplification was found by array comparative genomic hybridization in 23% (3/13) of analysed FTCs and all showed overexpression. HER-2/neu overexpression also occurred without DNA copy number changes in three other cases. For p27(Kip1), expression and DNA copy number were unrelated. p53 accumulation and p27(Kip1) down-regulation seem to be early events in Fallopian tube carcinogenesis. HER-2/neu showed overexpression, caused by gain/amplification in 50%, and may be involved in progression of FTC. These data contribute to a better understanding of the molecular carcinogenesis of FTC and to possible new therapeutic approaches.

DNA profiling of primary serous ovarian and Fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation‐dependent probe amplification

Primary serous ovarian carcinoma (OVCA) and serous Fallopian tube carcinoma (FTC), both belonging to the BRCA-linked tumour spectrum, share many properties and are treated similarly. However, a detailed molecular comparison has been lacking. We hypothesized that comparative genomic studies of serous OVCAs and FTCs should point to gene regions critically involved in their tumorigenesis. Array comparative genomic hybridization (array CGH) analysis indicated that serous OVCAs and serous FTCs displayed common but also more distinctive patterns of recurrent changes. Targeted gene identification using a dedicated multiplex ligation-dependent probe amplification (MLPA) probe set directly identified EIF2C2 on 8q as a potentially important driver gene. Other previously unappreciated gained/amplified genes included PSMB4 on 1q, MTSS1 on 8q, TEAD4 and TSPAN9 on 12p, and BCAS4 on 20q. SPINT2 and ACTN4 on 19q were predominantly found in FTCs. Gains/amplifications of CCNE1 and MYC, often in conjunction with changes in genes of the AKT pathway, EVI1 and PTK2, seemed to be involved at earlier stages, whereas changes of ERBB2 were associated with advanced stages. The only BRCA1-mutated FTC shared common denominators with the sporadic tumours. In conclusion, the data suggest that serous OVCAs and FTCs, although related, exhibit differences in genomic profiles. In addition to known pathways, new genes/pathways are likely to be involved, with changes in an miRNA-associated gene, EIF2C2, as one important new feature. Dedicated MLPA sets constitute potentially important tools for differential diagnosis and may provide footholds for tailored therapy.

Clues to the pathogenesis of fallopian tube carcinoma: a morphological and immunohistochemical case control study.

The purpose of this study was to identify histopathological fallopian tube changes that might be related to the development of fallopian tube carcinoma (FTCA). Each of 14 unilateral cases of the latter was matched with 2 controls for age, hospital, and year of diagnosis. The uninvolved fallopian tube from patients with FTCA, all of which were of serous type, was compared to fallopian tubes from the same side in 28 matched controls. The features evaluated included plical bridging, trapped gland-like structures, inflammation, epithelial stratification, tufting, nuclear atypia, plical atrophy, luminal dilatation, and presence or absence of in situ carcinoma. The significant changes (p < 0.05) in the contralateral tubes of patients with FTCA were luminal dilatation (p = 0.0004), plical atrophy (p = 0.0015), and chronic inflammation (p = 0.0089). FTCA may therefore develop in tubes demonstrating histologic features of chronic healed salpingitis, findings that reflect bilateral tubal disease which apparently antedates the development of the FTCA. p53 stains were strongly positive in 9 of 14 FTCAs and in 5 of 6 foci of in situ carcinoma found in the tubes with unilateral FTCA. No p53 staining was found in any of the contralateral tubes. Serous FTCAs may be etiologically related to antecedent bilateral healed chronic salpingitis and arise from in situ carcinoma in a background of atrophy.