Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia

Abstract

Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.

Stromal p16 expression is significantly increased in endometrial carcinoma

“…In addition, both EC and AH/EIN exhibited significantly higher stromal p16 expression levels compared with hyperplasia without atypia or endometrial polyp. This result was opposite to that of the previous study by Moritani et al [28]. We attribute these differences to the following two reasons.…”

“…We found one previous study reporting stromal p16 expression in endometrial neoplastic lesions [28]. For 80.0% (28/35) of endometrial polyp cases, p16 immunoreactivity with moderate or greater intensity was observed in fibrous stroma, and 1 (3.0%; 1/33) case of endometrial hyperplasia showed weak p16 expression; however, none of the endometrial carcinoma cases (0.0%; 0/23) showed stromal p16 expression.…”

“…For 80.0% (28/35) of endometrial polyp cases, p16 immunoreactivity with moderate or greater intensity was observed in fibrous stroma, and 1 (3.0%; 1/33) case of endometrial hyperplasia showed weak p16 expression; however, none of the endometrial carcinoma cases (0.0%; 0/23) showed stromal p16 expression. Moritani et al [28] stated that stromal p16 expression was a characteristic finding of endometrial polyps and was useful in differentiating between endometrial hyperplasia and endometrial polyps. These results are inconsistent with our findings that stromal p16 expression is significantly higher in precancerous and malignant lesions than in benign lesions.…”

“…First, two different sets of tissue samples were obtained from Japanese and Korean patients, and stromal p16 expression patterns may be race-specific. Second, p16 overexpression was observed in benign tumors such as benign nevus, neurofibroma, and schwannoma, which are related to oncogene-induced cellular senescence [28]. Thus, p16 overexpression in benign lesions inhibits cellular proliferation, protecting cells from malignant transformation [6].…”

Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a

“…On this basis, we proposed that the accumulation of senescent cells in EC tissue suppresses the progression of cancer. In accordance with previous reports that p16 INK4a expression is upregulated in endometrial polyps compared to endometrial hyperplasia due to the p16-induced cellr senescence (23), our functional investigations indicated that p16…”