p16 is consistently expressed in endometrial tubal metaplasia.
ABSTRACT Cell cycle proteins and HIF-1alpha with downstream factors are often abberrantly expressed in (pre)neoplastic tissue.
Paraffin-embedded specimens of inactive endometrium with TM (n=15), ovarian inclusion cysts (n=6), cervix with TM (tubal metaplasia) (n=3), Fallopian tubes (n=7), cycling endometrium (n=9) and a ciliated cell tumor of the ovary were stained for p16 and LhS28. 39 Endometrioid endometrial carcinomas and 5 serous endometrial carcinomas were stained for p16. Additionally, inactive endometrium (n=15) was immunohistochemically stained for p21, p27, p53, cyclin A, cyclin D1, cyclin E, HIF-1alpha, CAIX, Glut-1 and MIB-1.
A mosaic pattern of expression of p16 was seen throughout in all cases of endometrial TM (15/15), in 2/6 of the ovarian inclusion cysts with TM, in all (3/3) cervical TM and focal in 5/7 of Fallopian tube cases. Mosaic expression was also seen in a ciliated cell tumor of the ovary and in 18/39 of endometrioid endometrial carcinomas, and diffuse p16 expression was seen in 5/5 serous carcinomas. In comparison with normal endometrium, TM areas in the endometrium showed significantly increased expression of HIF-1alpha, cyclin E, p21 and cyclin A, and decreased expression of p27. Membranous expression of CAIX and Glut-1 was only seen in TM areas, pointing to functional HIF-1alpha.
As p16 is consistently expressed in TM, less and only patchy expressed in the normal Fallopian tube, is paralleled by aberrant expression of cell cycle proteins, HIF-1alpha, CAIX and Glut-1 and resembles the pattern of p16 expression frequently seen in endometrial carcinomas, we propose endometrial TM to be a potential premalignant endometrial lesion.
SourceAvailable from: Sebastian TheurichExpert Review of Anti-infective Therapy 03/2013; 13(3):243-5. DOI:10.1586/era.12.175 · 2.28 Impact Factor
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ABSTRACT: Despite the well-established role of hypoxia in cancer biology, the literature on its effects on endometrial cancer is scarce; it mainly refers to experimental settings rather than patient-derived results. Herein, an overview of the hypoxia inducible factor 1α (HIF-1α) biology, focusing on endometrial cancer, is presented. The molecular mechanisms possibly involved in endometrial cancer progression are presented, followed by a systematic approach to the current literature on immunohistochemistry evaluation of HIF-1α expression in endometrial carcinoma. Since no consensus has been made regarding HIF-1α evaluation, the evidence of possible involvement of HIF-1α in endometrial carcinoma prognosis is weak. After a consensus has been made, properly powered studies may be able to clarify whether HIF-1α can act as a prognosticator in endometrial carcinoma.Histology and histopathology 10/2012; 27(10):1247-53. · 2.24 Impact Factor
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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.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2012; 461(2):141-8. DOI:10.1007/s00428-012-1276-1 · 2.56 Impact Factor