Purpose:Women who have inherited germline mutations of BRCA1/BRCA2 are at increased risk of developing High Grade Serous Carcinoma, and many of these cancers arise in the distal fimbriated end of the fallopian tube. In this study, we sought to determine whether there is a proliferative advantage and a differential abundance of immune cells in the epithelia in this high-risk population. Experimental Design:Immunohistochemistry for Ki67, CD3, CD8, CD20 and CD68 was performed on histologically normal tubal epithelium with known ovarian cycle status and germline mutation status. Serous tubal intraepithelial carcinomas (STIC) with concomitant cancer (n=15) were also analyzed for presence of immune infiltrates. All slides were digitized and analyzed using automated image analysis software. Results:There was no significant difference in the proliferative index in histologically normal FTE between BRCA1/BRCA2 and non-BRCA. More macrophages were present in the luteal phase compared to the follicular phase epithelia. In STICs macrophages were more abundant than lymphocytes with an incremental increase noted with disease progression. Conclusions: BRCA1/2 mutation carriers exhibited no significant increase in proliferation in the fallopian tube epithelial cells either in the ampulla or fimbriated ends of the tube. Rather, significant proliferative increase was defined in the cases determined to be in the pre-ovulatory phase of the ovarian cycle. Lastly, we also demonstrate an incremental increase in leukocytes invading the STICs and HGSC, implicating a possible role for of the leukocytes early in the progression or inhibition of tumor formation, independent of ovarian cycle.
- Received June 27, 2012.
- Revision received August 29, 2012.
- Accepted August 30, 2012.
- Copyright © 2012, American Association for Cancer Research.