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Background Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome for high-grade serous ovarian cancer (HGSOC) patients. Treatment of HGSOC patients with neoadjuvant chemotherapy, however, may select for tumor cells harboring alterations in hallmark cancer pathways including metastatic potential. This study assessed this hypothesis by performing proteomic analysis of matched, chemotherapy naïve and neoadjuvant chemotherapy (NACT)-treated HGSOC tumors obtained from patients who had suboptimal (R1, n = 6) versus optimal (R0, n = 14) debulking at interval debulking surgery (IDS). Methods Tumor epithelium was harvested by laser microdissection from formalin-fixed, paraffin-embedded tissues from matched, pre- and post-NACT treated tumors for twenty HGSOC patients and analyzed by quantitative mass spectrometry-based proteomics. Results Differential analysis of patient matched pre- and post-NACT treated tumors revealed proteins associated with cell survival and metabolic signaling to be significantly altered in post-NACT treated tumor cells. Comparison of pre-NACT treated tumors from suboptimal (R1) versus optimally (R0) debulked patients identified proteins associated with tumor cell viability and invasion signaling enriched in R1 patients. We identified five proteins altered between R1 and R0 patients in pre- NACT treated tumors that significantly correlated with PFS in an independent cohort of HGSOC patients, including Fermitin family homolog 2 (FERMT2), a protein elevated in R1 that correlated with disease progression in HGSOC patients (multivariate Cox HR = 1.65, Wald p = 0.022) and increased metastatic potential in solid-tumor malignancies. Conclusions This study identified distinct proteome profiles in patient matched pre- and post-NACT HGSOC tumors that correlate with NACT resistance and that may predict residual disease status at IDS that collectively warrant further pre-clinical investigation.

Objective To describe the factors and attributes that obstetrics and gynecology fellowship directors use in selecting applicants for interview and ranking. Methods Anonymous questionnaires were completed by obstetrics and gynecology fellowship directors using a web-based survey (adapted from a previously published questionnaire) before match day 2011. Fellow selection practices were evaluated and included importance of prematch preparations, screening of applications, interview processes, and recommendations given to applicants. Fellowship directors were asked to grade selection factors based on a 5-point Likert-like scale (ranging from 1 being unimportant to 5 being essential). Results A total of 187 fellowship directors representing programs accredited by the American Board of Obstetrics and Gynecology, Inc. were surveyed, and 124 completed the survey (66% response rate). The factors in prematch preparations that 99-100% of program directors found in the essential to important range were a high-quality obstetrics and gynecology residency training program and experience with clinical research during residency or with clinical research after residency. Surgical experience was valued more by gynecologic oncologist respondents than by other subspecialty respondents, although this statistic did not reach statistical significance (P=.08). Conclusion Education pedigree and research experience are important factors considered by fellowship directors when selecting fellowship applicants. For applicants, these data will allow for a critical self-analysis before applying or interviewing.

OBJECTIVE : To evaluate qualifications of successful applicants to Female Pelvic Medicine and Reconstructive Surgery (FPMRS) fellowship programs. METHODS : A 55-point web-based survey was sent to 49 applicants participating in the 2008 FPMRS Match. RESULTS : The survey achieved a 59% response rate, with a total of 29 respondents. Regarding prematch educational preparations pursued by applicants, 11 of the 24 matched respondents (46%) trained at residencies that offered FPMRS fellowship training. About 19 matched applicants (19/21, 90%) and 2 unmatched applicants (2/5, 40%) received a letter of recommendation from a "nationally-known" female pelvic medicine surgeon. About 40% of matched and unmatched applicants authored at least one manuscript. CONCLUSIONS : If these respondents are representative of all fellowship candidates in FPMRS match, then it would be expected that combined application costs for all candidates would be almost $350,000.

Objective: Uterine carcinosarcoma (UCS) is an aggressive malignancy, making up less than 5% of uterine cancers. Pharmacologic inhibition of ATR kinase synergistically enhances the ability of cisplatin to kill carcinoma cells of many solid tumor types and is further enhanced in ATM low carcinoma cells. It is unknown whether ATR inhibition (ATRi) offers a therapeutic opportunity in UCS. The goal of this study was to evaluate ATM expression in UCS tumors and determine the response of an ATM low UCS model to ATRi + cisplatin combination. Methods: ATM expression was evaluated in full tissue sections from 74 UCS tumors by immunohistochemistry (IHC) with an ATM specific monoclonal antibody (clone Y170, Abcam), and was categorized as negative vs any positive staining in the carcinomatous (C) vs sarcomatous (S) components. In vitro models of UCS: SK-UT-1, SK-UT-1B, KLE, and RL95-2 cell lines were treated with an ATRi (AZD6738), cisplatin, and ATRi + cisplatin. ATM low models were generated in RL95-2 cells using short hairpin RNA (shRNA) lentivirus targeting ATM and a non-target control. Cells were subjected to cisplatin and ATRi dose response analyses. Results: Negative IHC expression of ATM protein was observed in 24% of the C vs 31% of the S components of the 74 UCS cases (Table 1). ATRi increased the sensitivity of uterine carcinosarcoma cell line models to cisplatin. Western blot confirmed a 57% knockdown in ATM in RL95-2 cells infected with shRNA for ATM and treatment with ATRi +cisplatin therapy showed ~20% increase in cell death in ATM low vs control cells lines, p=0.02. Conclusions: IHC analyses of UCS tumors showed an average of ~27% of tumors have loss of ATM in C and S components. Preliminary evidence shows that ATRi increases the sensitivity of UCS cell models to cisplatin therapy, which is further increased in ATM low uterine carcinoma cells. These findings suggest a novel therapeutic opportunity for ATRi + cisplatin therapy in UCS patients with low ATM expressing tumors. Immunohistochemistry-based quantification of ATM expression in uterine carcinosarcoma tumorsATMUterine CarcinosarcomaIntensityCarcinomatous ComponentSarcomatous component0-131 (41.9%)33 (44.6%)018 (24.3%)23 (31.1%)113 (17.6%)10 (13.5%)2-343 (58.1%)41 (55.4%)211 (14.9%)10 (13.5%)332 (43.2%)31 (41.9%)TOTAL7474 Citation Format: Emily R. Penick, Paulette Mhawech-Fauceglia, Nicholas Bateman, Kelly Conrads, Tracy Litzi, Chunqiao Tian, Chad A. Hamilton, Kathleen Darcy, George Maxwell, Thomas Conrads. Inhibition of the ATR kinase enhances therapeutic efficacy of cisplatin in ATM low uterine carcinosarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2359. doi:10.1158/1538-7445.AM2017-2359

We report the attributes of Female Pelvic Medicine and Reconstructive Surgery (FPMRS) fellowship applicants that are most valued by fellowship program directors during the ranking process.Anonymous questionnaires were filled out by FPMRS fellowship program directors following the 2008 match. The survey was designed to assess the relative importance of various factors in the ranking of fellowship applicants.Surveys were sent to 67 program directors, and 21 completed the survey (31%). Items ranked as the most important in the selection process were a high quality obstetrics and gynecology residency education (8.2+/-1.2), followed by clinical research experience (7.4+/-1.4). Ability to work well with staff and work ethic were considered to be the most important subjective criteria.Our results support anecdotal evidence that placed emphasis on research experience and interpersonal skills in the selection of FPMRS fellows.