Abstract 3146: Changes in expression of nuclear protein nucleolin detects malignant changes in the fimbria and offers a potential marker for early detection of ovarian cancer

Abstract

Abstract Introduction: Ovarian cancer (OVCA) remains a fatal malignancy of women as in most cases it is detected at late stages. Fimbria of the fallopian tube has been suggested to be the origin of high grade serous carcinoma (HGSC) and lack of information on the malignant transformation of fimbrial surface epithelial (FSE) cells is a significant barrier to the development of an early detection test for OVCA. The nucleus of a cell has long been used in the pathology for the detection of malignancy. Tumor-associated changes in the nucleus are accompanied by a rearrangement in the nuclear matrix proteins and shedding of these proteins into the circulation. These shed proteins or autoantibodies against them represent markers of early changes for early detection of OVCA. Goals: The goal of this study was to examine the changes in the serum prevalence of nucleolin, a nuclear protein, in association with malignant changes in the FSE cells and ovarian malignant development. Due to the difficulty in accessing the fimbria from OVCA patients, we used laying hen models of spontaneous OVCA. Methods: This was an exploratory pilot study with subjects/patients and a laying hen model of spontaneous OVCA. In the first study, expression of nucleolin was examined in the fimbrial tissues from subjects (BRCA1 mutated) with risk of OVCA development who underwent prophylactic surgery (n=5, 40-50 years old) and ovarian tumors from OVCA patients at early stage (n=5, 60-70 years old). In the second study, serum, fimbrial and ovarian tissues from healthy laying hens (n=10, 4-year old), hens with fimbrial tumors (n=5) and hens with OVCA at late stage (n=10) were also used. Expression of nucleolin was examined by immunohistochemistry, Western blotting, proteomic (MS-MS) and gene-expression studies. Significant differences (P<0.05) in the intensity of nucleolin expression among normal as well as fimbrial and ovarian tumor groups were determined. Results: Intense expression for nucleolin was observed in the fimbrial surface epithelial (FSE) cells from subjects with BRCA1 mutation and in malignant cells in ovarian tumors from OVCA patients. Similar patterns of nucleolin expression were also detected in fimbrial tumors and ovarian tumors at late stage in hens. Two-dimensional Western blotting detected nucleolin protein of approximately 76kDa in fimbrial tumors in hens. MS-MS study showed spectra for nucleolin indicative of its serum prevalence in hens with fimbrial tumors and ovarian tumors. Semi-quantitative and quantitative PCR showed strong amplification for nucleolin gene expression in fimbrial and ovarian tumors in hens as compared with normal fimbria. Conclusion: Expression of nucleolin increases in association with malignant transformation in the fimbria and ovarian tumor development. Serum prevalence of nucleolin suggests that it may be used as a marker of early changes associated with OVCA development and may constitute a member of a panel of markers for early detection of OVCA. Support: NIH/NCI: CA210370 Citation Format: Elizabeth A. Paris, Itzel Lazcano, Pincas Bitterman, Janice Bahr, Sanjib Basu, Animesh Barua. Changes in expression of nuclear protein nucleolin detects malignant changes in the fimbria and offers a potential marker for early detection of ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3146.