title: Inhibition of autophagy in peripheral blood mononuclear cells by vaginal fluid from women with a malignant adnexal mass.
abstract: Inhibition of autophagy is a characteristic of ovarian cancer. We determined whether inhibition of autophagy by vaginal fluid could provide a non-invasive test for cancer risk stratification in women presenting with an adnexal mass. Vaginal fluid supernatants from 90 women undergoing evaluation for a suspicious adnexal mass were incubated with peripheral blood mononuclear cells (PBMCs) obtained from healthy women under conditions that induce autophagy. Rapamycin, an autophagy inducer, was added to some cultures. After 48 hr the cells were collected, lysed and assayed by ELISA for intracellular p62 concentration. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration is inversely proportional to the extent of autophagy induction. Clinical information including pathological diagnoses was obtained after completion of laboratory studies. Mean p62 levels were 9.4 ng/ml in the 21 women with a subsequent malignant diagnosis, 4.5 ng/ml in the eight women with a borderline tumor diagnosis and 3.6 ng/ml in the 61 women with benign disease (p < 0.0001, malignant vs. others). When rapamycin was added to the vaginal fluid-PBMC co-incubation, p62 levels in samples from women with a malignant diagnosis decreased to 3.3 ng/ml, a level comparable to what was observed with the nonmalignant samples. Vaginal fluid inhibition of autophagy can differentiate between women with malignant and benign adnexal masses.
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Theofano
authors.initials: T
authors.lastname: Orfanelli
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Georgios
authors.initials: G
authors.lastname: Doulaveris
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Kevin
authors.initials: K
authors.lastname: Holcomb
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Jiyeon M
authors.initials: JM
authors.lastname: Jeong
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sisti
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Tomi T
authors.initials: TT
authors.lastname: Kanninen
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Caputo
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Divya
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Witkin
mesh_terms: D000328:Adult; D000368:Aged; D001343:Autophagy; D014408:Biomarkers, Tumor / Q000378:metabolism; D001826:Body Fluids; D002478:Cells, Cultured; D005260:Female; D005833:Genital Neoplasms, Female / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000378:metabolism; D012372:ROC Curve; D014621:Vagina / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C118585:P62 protein, human; D016601:RNA-Binding Proteins
keywords: adnexal mass; autophagy; malignancy; p62; vaginal fluid