Secretory Cell Expansion of the Fallopian Tube Epithelium May Represent an Initial Cellular Change in Pelvic Serous Carcinogenesis.
Nisreen AbuShahin, Li Xiang, Oluwole Fadare, Beihua Kong, Wenxin Zheng. University of Arizona Collage of Medicine, Tucson; Vanderbilt University School of Medicine, Nashville, TN; Qilu Hospital, Shandong University, Jinan, Shandong, China
Background: The distal fallopian tube is a common site of origin for tubal intraepithelial carcinoma and pelvic serous carcinoma in high-risk women (i.e BRCA mutation carriers and/or those with a breast cancer history). It has recently been further defined at the cellular level, that the secretory cell as opposed to cililated cell of the fallopian tube is the cell-of-origin of these cancers. However, under normal conditions, secretory and ciliated cells are intimately admixed within the tubal epithelial lining. We hypothesized that a change in ratio between tubal secretory and ciliated cells may represent one of the early steps in the process of female pelvic serous carcinogenesis
Design: Cellular compositions (secretory versus ciliated) in fallopian tubal segments (fimbriated end versus ampulla), secretory cell expansion (> 10 but < 30 cells in a row) and secretory cell outgrowth (≥ 30 cells in a row) were studied in 3 groups of patients: patients with benign gynecologic diseases (“no-risk”), “high-risk” patients as previously defined, and patients with “ovarian” high-grade serous carcinomas. The numbers of secretory and ciliated cells were counted by 2 methods: light microscopy and immunostainings with PAX8 for secretory cells and tubulin for ciliated cells. The ratio of cellular compositions was statistically compared among the 3 groups
Results: As compared with the “no risk” group, the numbers of tubal secretory cells in the high-risk and cancer groups were increased by a factor of at least 2 and 4 respectively. The frequency of secretory cell expansion was 3 to 4-fold higher in the high-risk and cancer groups, while the frequency of secretory cell outgrowth was 4-fold higher in the high-risk and 6-fold higher in the cancer group, respectively. Overall, immunohistochemistry with PAX8 and tubulin was more sensitive than morphologic evaluation for distinguishing the cell types. There was no significant difference between the tubal fimbriated end and ampulla regarding the number of secretory cells
Conclusions: An increase in the number of secretory cells in fallopian tube epithelium may represent an early, morphologically identifiable event in the process of pelvic serous carcinogenesis, although the underlying molecular mechanism of secretory cell expansion or outgrowth and how they eventuate in cancers, remain unclear.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 11:15 AM
Platform Session: Section D, Tuesday Morning