Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression

Abstract

Endometrial carcinoma is a common malignancy of the female genital tract. Alterations in the expression levels of various oncogenes and tumor suppressor genes serve important roles in the carcinogenesis and biological behavior of endometrial carcinoma. The aim of the present study was to evaluate the combination and individual expression of p53 and phosphatase and tensin homolog (PTEN) protein in human endometrial carcinoma. In addition, the correlation of these proteins with clinicopathological parameters was also assessed. Retrospective immunohistochemical analysis of the expression of p53 and PTEN tumor suppressor proteins was conducted in 99 women with endometrial carcinoma. The overall rate of p53 and PTEN positivity was 89 and 77%, respectively, according to the sum of stain intensity and scores of immunopositive cells. The sum of p53 positivity correlated strongly with PTEN expression (ρ=0.256; P=0.044). The concomitant sum of p53 and PTEN expression was identified in 45% of patients with endometrial adenocarcinoma. Notably, the sum of the immunohistochemical expression of p53 was significantly correlated with patient age (P=0.037), histologic type (P=0.008), histologic grade (P=0.002) and fallopian and/or ovarian invasion (P=0.014). Furthermore, PTEN expression was associated with myometrial invasion (ρ=−0.377; P=0.002) and clinical stage (P=0.019). In addition, concomitant p53 and PTEN expression was correlated with patient age (P=0.008) and histologic differentiation (P=0.028). The findings indicated a correlation between the expression of p53 and PTEN in endometrial adenocarcinoma, which suggested an intrinsic association between expression levels of these tumor suppressor genes. The study also suggested that concomitant p53 and PTEN expression contributed in characterizing the tumor behavior of endometrial carcinoma. Taken together, the present study suggested the combined expression of p53 and PTEN in the development of high-grade endometrial carcinoma in older patients. In addition, the findings indicated activation of different molecular pathways in the tumor progression between low-grade and high-grade endometrial carcinomas.

Expression of anti‑apoptotic protein survivin in human endometrial carcinoma: Clinical and pathological associations as a separate factor and in combination with concomitant PTEN and p53 expression

“…We therefore suggested that the concomitant expression of p53 and PTEN may play a role in the development of high-grade endometrial carcinomas in older patients (43). In addition, these findings suggested the involvement of different molecular pathways in the development of low-and high-grade endometrial carcinomas (43). In the present study, a negative tendency was identified between the scores of survivin and PTEN expression (P=0.062, ρ=-0.238).…”

“…In the present study, we investigated the effects of immunohistochemical PTEN and p53 expression on the expression of survivin in endometrial carcinomas. In our previous study we investigated the distribution of tumor suppressor genes p53 and PTEN in primary endometrial carcinoma specimens acquired from Greek patients and analyzed the clinical significance of the combination of p53 and PTEN expression (43). We believe that the present findings are interesting, since the clinical significance of the interplay between the expression of the tumor suppressor genes PTEN and p53, and survivin in endometrial carcinomas remained unknown so far.…”

“…In our previous study the levels of p53 and PTEN co-expression were found to be correlated with patient age (P=0.08) and histological differentiation (P= 0.028), according to the scores of immunopositive cells. We therefore suggested that the concomitant expression of p53 and PTEN may play a role in the development of high-grade endometrial carcinomas in older patients (43). In addition, these findings suggested the involvement of different molecular pathways in the development of low-and high-grade endometrial carcinomas (43).…”

“…Clinicopathological and immunohistochemical study of endometrioid, papillary serous and clear cell endometrial adenocarcinomas. The clinicopathological data of our study was previously described and reported (43). The specimens included 20 endometrioid endometrial carcinomas of histological grade 1 (G1), 47 of G2 and 19 of G3, as well as 13 papillary serous carcinomas or clear cell carcinomas.…”

Value of p53 and estrogen receptors immunohistochemical staining in endometrial carcinoma

“…However, there is opinion that over expression of wildtype gene and presence of mutant p53 show different staining patterns and that diffuse nuclear staining in more than 80% of cells is indicative for presence of mutation. 16,17 Determining ER status may be useful in treatment planning, but there is no clear cut-off above which tumor should be considered ER positive. Many studies are using scoring systems based on complex calculations and evaluation of both intensity and extent, which is complicated and prone to inter-observer variability.…”