Proteomic alterations associated with residual disease in neoadjuvant chemotherapy treated ovarian cancer tissues.

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.

Human epididymis protein 4: Analysis of national health and nutrition examination survey data.

BACKGROUND: Human epididymis protein 4 (HE4) is a tumor marker overexpressed in ovarian cancer and is commonly utilized to aid with diagnosis of an adnexal mass. HE4 levels vary based on pregnancy, age, menopausal status, and tobacco use. OBJECTIVE(S): The objective of this study was to evaluate population-based data to examine factors that affect HE4 among adult women in the United States and stratify levels of HE4 by demographic and gynecologic factors. STUDY DESIGN: A retrospective analysis was conducted using data from 2,480 women aged 20 + who participated in the National Health and Nutrition Examination Survey (2001-2002). From these cross-sectional data, serum HE4 and cotinine, a marker of tobacco exposure, were combined with demographic and interview data. Estimated glomerular filtration rates (eGFR) were based on serum creatinine, age, sex, and race. Other variables of interest included menopausal status, pregnancy, and various gynecologic factors. Summary HE4 data are provided as geometric means with associated 95 % confidence intervals. RESULTS: HE4 levels were independently associated with age, renal function, and nicotine use, all p < 0.001. Pre-menopausal women with a history of endometriosis were found to have elevated HE4 levels compared to those without, p < 0.01; however, we found no such difference among post-menopausal women. Adjusting for age, no differences in HE4 were found based on race/ethnicity, p = 0.29. HE4 levels showed statistically significant associations with income level; however, these were small and clinically irrelevant. CONCLUSION: This study provides evaluation of HE4 levels among a data set representative of 98.5 million non-institutionalized women in the United States and gives insight into extraneous factors that may influence these levels.

Factors used by female pelvic medicine and reconstructive surgery fellowship directors to select their fellows.

INTRODUCTION AND HYPOTHESIS: We report the attributes of Female Pelvic Medicine and Reconstructive Surgery (FPM&RS) fellowship applicants that are most valued by fellowship program directors during the ranking process. METHODS: Anonymous questionnaires were filled out by FPM&RS 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. RESULTS: 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. CONCLUSIONS: Our results support anecdotal evidence that placed emphasis on research experience and interpersonal skills in the selection of FPM&RS fellows.

Attributes of successful and unsuccessful female pelvic medicine and reconstructive surgery fellowship applicants.

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.