Immunohistochemical study of PTEN and survivin in endometrial proliferative lesions

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Abstract

Proliferative lesions of the endometrium are a heterogenous group of lesions with variable pathological, clinical, epidemiological, and genetic properties. The phosphatase and tensin (PTEN) homolog is deleted on the chromosome 10 tumor suppressor gene. PTEN regulates cell growth, apoptosis, and proliferation. Survivin called Baculoviral inhibitor of apoptosis repeat-containing 5 is a member of the inhibitor of the apoptosis family of antiapoptotic proteins. The aim of this study was to investigate the expression of PTEN and survivin in different proliferative endometrial lesions and to study their correlation with classical prognostic factors. This study was performed on 50 cases of proliferative endometrial lesions selected from the histopathological files of AL-Zahraa university hospital and from the archives of the histopathology private Labs of pathology in the period between 2006 and 2009. These cases were categorized as follows: five cases of disordered proliferative endometrium, three cases of endometrial polyps, 11 cases of simple and complex endometrial hyperplasia without atypia, six cases of simple and complex endometrial hyperplasia with atypia, 19 cases of endometrial carcinomas, and six cases of malignant mixed mullerian tumors. Hematoxylin and eosin-stained paraffin sections were examined microscopically for histopathological evaluation. Sections were immunostained for PTEN and survivin for immunohistochemical evaluation. In the present study, endometrial thickness was more than 1 cm in most cases of endometrial carcinoma (EC) (73.7%) and less than 1 cm (80%) for most cases of endometrial hyperplasia (EH), and there was a significant difference between the endometrial thickness of EH and most cases of EC. Nearly half of the EC cases were grade III (52%). In this study, 48% of the malignant cases were preceded by atypical complex hyperplasia (as detected microscopically in the adjacent area); this was statistically significant. Most endometrial carcinomas and half of cases of MMMT; malignant mixed mullerian tumors showed invasion of more than 1/2 of the myometrium with no statistically significant difference between them. PTEN expression was observed in a total of 33 cases out of the total 50 cases with proliferative endometrial lesions (66%). PTEN expression was positive in all benign lesions and was positive in 16% of malignant lesions; thus, there was a highly significant difference between PTEN expression in benign and malignant lesions (P<0.001). PTEN expression in different grades of endometrial carcinomas showed no significant difference (P=0.166). This study revealed that survivin expression was detected in 40 out of the total 50 cases of proliferative endometrial lesions (80%). Survivin expression was positive in all malignant lesions and 60% of benign lesions were positive; thus, there was a significant difference between survivin expression in benign and malignant lesions (P<0.001). In terms of survivin expression in different grades of endometrial carcinoma, nearly half of the cases of grade III were strongly positive (54.55%), whereas 22.72% of cases of grades I–II were strongly positive; there was a significant difference between survivin expression and grades of endometrial carcinoma (P<0.001). From these results, it is clear that there was an inverse relationship between PTEN and survivin expression as PTEN expression increased in benign lesions and decreased to lost in malignant lesions, whereas survivin expression decreased to lost in benign lesions and increased in malignant lesions. The use of PTEN immunostaining in a clinical setting may be informative in identifying premalignant lesions as decreased PTEN expression is a marker of the earliest endometrial precancers. Survivin may participate in the onset and progression of endometrial carcinoma by inhibiting apoptosis and promoting proliferation. Survivin expression is correlated with the malignant grade and prognosis of tumors. Survivin may be an attractive target for endometrial cancer treatment.

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