Expression of βV-Tubulin in Secretory Cells of the Fallopian Tube Epithelium Marks Cellular Atypia

OBJECTIVES: Class V Beta tubulin isotype (βV-tubulin) was recently found to have tissue-specific expression patterns in epithelial tissues with secretory function and aberrant expression in tumors. The aims of this pilot study were (a) to examine expression of βV-tubulin in the fallopian tube epithelium (FTE) of patients who underwent salpingectomy, (b) to characterize FTE atypia in high-risk patients with BRCA mutations, and (c) to determine expression of βV-tubulin in serous ovarian neoplasms. METHODS: Immunohistochemistry, with a highly specific antibody developed in our laboratory against human βV-tubulin, was used to evaluate expression in paraffin-embedded sections of the fallopian tube (n = 82) and tumors (n = 13), from prospectively selected cases, categorized by reason for salpingectomy. RESULTS: βV-tubulin, when present, was expressed in secretory cells and essentially never in ciliated cells of the FTE. Histologically “normal” FTE had very rare, scattered βV-tubulin–positive cells; percentage positivity increased in cases of serous ovarian neoplasms. The highest expression was observed in FTE from patients with BRCA mutant breast cancer. Four distinct types of FTE atypia were delineated in patients with known BRCA mutations. In a few additional test cases of ovarian neoplasms, βV-tubulin was highly expressed, with the extent and intensity of staining elevated in high-grade serous carcinomas compared with serous borderline tumors. CONCLUSIONS: In summary, βV-tubulin was localized to secretory cells of the distal FTE and its expression varied according to the clinical diagnosis. The frequency of these cells and thus expression of βV-tubulin were dramatically enriched in tissue obtained from BRCA mutant cases, which also exhibited pronounced histologic atypia indicative of early predysplastic aberrations. Furthermore, elevated expression of βV-tubulin correlated with poor differentiation status in serous ovarian neoplasms.