Zorn Research Group

Principal Investigator: Kristin Zorn, MD

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. Fallopian tube and primary peritoneal cancers are related to EOC by similar histology and behavior. Recently, the care of women felt to be at high risk due to a strong family history of breast and/or ovarian cancer or a known BRCA1 or BRCA2 mutation has provided insight into these malignancies.

An unexpectedly high rate of fallopian tube cancer has been seen in high-risk women undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). This observation has focused attention on the fallopian tube as the possible source of EOC and has led to the hypothesis that tubal intraepithelial carcinoma may be an intermediary step in the development of serous gynecologic cancers, including those that traditionally have been thought to arise in the ovarian surface epithelium (OSE) or peritoneum.

The Gynecologic Oncology laboratory hypothesizes that the OSE, fallopian tube mucosa, and peritoneal surface express proteins or their post-translational modifications whose presence is predictive of precancerous and cancerous changes. The lab conducts a quantitative proteomic investigation of cells from women who undergo RRBSO. Cells obtained from lavaging and/or brushing the ovaries, fallopian tubes, and peritoneum are lysed and resulting proteins are digested with trypsin prior to analysis by high-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Relative quantification of differentially abundant proteins unique to the OSE, fallopian tube, and peritoneum will be established and cross-validated using advanced bioinformatics applications (e.g., statistically iterative exploratory visualization environment). These permit comparisons of the observed ion current (e.g., MS peak intensity) and are based on multivariate analysis, enabling statistically rigorous evaluation and direct quantification of peptide abundances from multiple LC-MS/MS datasets. If the specimen collection techniques allow adequate cellular recovery for proteomic investigation, the project will be expanded to allow differences in protein abundance to be analyzed between women without a family history of breast or ovarian cancer, those with such a history, and those with a known BRCA1 or BRCA2 mutation. Given the inadequacy of current screening techniques for EOC, identification of novel biomarkers for preinvasive or early-stage disease would revolutionize care.

Selected Publications

  • Zorn KK, Jazaeri AA, Awtrey C, Gardner GJ, Mok S, Boyd J, & Birrer MJ. Choice of normal ovarian control influences determination of differentially expressed genes in ovarian cancer expression profiling studies. Clin Cancer Res, 9(13):4811-18, 2003.
  • Jazaeri AA, Awtrey C, Chandramouli G, Chuang T, Khan J, Sotiriou C, Apelikova O, Yee C, Zorn KK, Birrer MJ, Barrett CJ, & Body J. Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers. Clin Cancer Res, 11(17):6300-10, 2005.
  • Zorn KK, Bonome T, Gangi L, Chandramouli G, Awtrey C, Gardner GJ, Barrett CJ, & Birrer MJ. Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res, 11(18):6422-30, 2005.
  • Dann RB, Kelley JL, & Zorn KK. Strategies for ovarian cancer prevention. Obstet Gynecol Clin North Am, 34:667-86, 2007.
  • Guirguis A, Elishaev E, Oh S, Tseng G, Zorn K, & DeLoia JA. Use of gene expression profiles to stage concurrent endometrioid tumors of the endometrium and ovary. Gynecol Oncol, 108:370-6, 2008.
  • Zorn KK, Tian C, McGuire WP, Hoskins WJ, Markman M, Muggia FM, Rose PG, Ozols RF, Spriggs D, & Armstrong DK. The prognostic value of pretreatment CA-125 in advanced ovarian carcinoma: A Gynecologic Oncology Group study. Cancer, 115:1028-35, 2009.

Publications on PubMed

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