Ki-67 and p53 expression of the fallopian tube mucosa in breast cancer patients with hereditary risk.

Purpose: The fallopian tube has been implicated as a site of origin of sporadic and BRCA1-related ovarian cancer. To investigate if Ki-67 or p53 is altered in BRCA1 mutation carriers, we have studied the expression of these markers in morphologically normal mucosa in the fallopian tube and fimbriae.

Methods: Prophylactic adnexectomy specimens from 24 patients (eight BRCA1 mutation carriers, eight non-mutation carriers, and eight with unknown BRCA1 status), were scored by automated image analysis for the amount of Ki-67 and wild-type p53 expression. All patients had a history of breast cancer and a family history of breast or ovarian cancer.

Results: In the fimbriae, a median of 0.42 % Ki-67 and 0.04 % p53-positive epithelial cells was present, compared to a median of 0.36 % for Ki-67 and 0.05 % for p53 in the fallopian tube. Ki-67 expression decreased significantly with age (r = -0.45, p = 0.028). In contrast, p53 expression was not age-dependent for the whole group of patients (r = 0.25, p = 0.25). Subgroup analysis revealed a difference for p53 expression of the BRCA1 mutation carriers with respect to age (median 0.039 vs. 0.082 % for age less or greater than 50.5 years). Consequently, the p53/Ki-67 ratio showed an age-dependent increase, which was accelerated in the BRCA1-positive patients.

Conclusions: Ki-67 and p53 expression varies in morphologically normal tubal epithelial cells depending on age and BRCA1 mutation status. This may reflect an altered and age-dependent DNA repair in BRCA1 mutation carriers and may be related to increased risk of ovarian cancer arising in the fallopian tube.