Morphological and immunohistochemical study of ovarian and tubal dysplasia associated with tamoxifen

Abstract

Ovarian epithelial dysplasia was initially described in material from prophylactic oophorectomies for BReast CAncer gene (BRCA) mutation. Similar histopathological abnormalities have been revealed after ovulation stimulation. Given that tamoxifen (TAM) has a clomid-like effect and is sometimes used to induce ovulation, we studied the morphological features and immunohistochemical expression patterns of neoplasia-associated markers in adnexectomies previously exposed to TAM for breast cancer. We blindly reviewed 173 histopathological slides of adnexectomies according to three groups - oophorectomie sassociated with TAM exposure (n=42), oophorectomies associated with clomiphene exposure (n=15) and a spontaneously fertile non cancerous control group (n=116). Morphological features (with an ovarian and tubal dysplasia scoring system) and immunohistochemical expression patterns of Ki-67, p53 and Aldehyde dehydrogenase 1 (ALDH1 is an enzyme significantly associated with earlystage ovarian cancer) were evaluated and correlated. Mean tubal dysplasia score was significantly higher in the TAM group and clomiphene group than in controls (respectively 7.8 vs 3.5, P<0.007 and 6.8 vs 3.5, P=0.008). There is no statistical difference for the ovarian score in TAM group in comparison with the control group whereas we found a significant score for clomiphen group (6.5, P=0.009). Increased ALDH1 expression was observed in the two exposed group whereas expression patterns of Ki67 and p53 were moderate. Interestingly, ALDH1 expression was low in non-dysplastic epithelium, high in dysplasia, and constantly low in the two carcinoma. Furthermore, we confirm our previous results showing that ALDH1 may be a useful tissue biomarker in the subtle histopathological diagnosis of tubo-ovarian dysplasia.

Figure 1.

Ki67, p53 and ALDH1 immunoreactivity in ovary; left column, after treating with tamoxifen; center column, after treating with clomid; right column, untreated control group. a-c) Immunoreactivity for Ki67; note the absence of Ki67 expression in all the three representative groups. d-f) Immunoreactivity for p53; p53 expression is low in the ovarian epithelium exposed to tamoxifen; in contrast, there is no p53 expression in ovary exposed to clomid and in the control group. g-i) immunoreactivity for ALDH1; the expression of ALDH1 is strong in ovaries exposed to tamoxifen and clomid, whereas no immunopositivity for ALDH1 was observed in the control group; intense staining for ALDH1 was noted in stroma (internal control). Scale bars: 100 µm.

Figure 2.

Ki67, p53 and ALDH1 immunoreactivity in fallopian tube; left column, after treating with tamoxifen; center column, after treating with clomid; right column, untreated control group. a-c) Immunoreactivity for Ki67; note the moderate expression of Ki67 in the tubes exposed to tamoxifen and clomid, and the low expression in the control group. d-f) Immunoreactivity for p53; the expression of p53 is weak in the tubes exposed to tamoxifen and clomid, and not present in the control group. g-h) ALDH1 immunoreactivity; note the strong expression of ALDH1 in the tubes exposed to tamoxifen and clomid, and the low or absent expression in the control group; also note the on/off effect of ALDH1 expression in panel h, where ALDH1 is mainly detected in the secretory cells lining but not in the ciliated cells. Scale bars: 100 µm.