PTEN Expression in Breast and Endometrial Cancer: Correlations with Steroid Hormone Receptor Status

Abstract

Objective: The PTEN (MMAC1/TEP1) tumor suppressor gene is frequently mutated and homozygously deleted in human neoplasms, but there is only sparse information about PTEN protein expression in hormone-dependent female tumors. Therefore, we investigated PTEN expression in 68 breast and 43 endometrial carcinomas. Methods: For PTEN protein detection, we used Western blot analysis followed by densitometry and compared these data with clinicopathologic parameters, the estrogen receptor (ER) and progesterone receptor (PR) status, HER2/neu and the proliferation marker Ki67. Results: We were able to show significantly decreased PTEN protein expression in endometrial carcinomas compared with normal endometrial tissue samples, especially in the endometrioid histological subtype. In contrast, PTEN downregulation was found more rarely in breast cancer. Lower PTEN expression in breast cancer correlated significantly with high ER immunoreactivity (p = 0.008) and was weakly associated with PR expression (p = 0.055) and low histological grading (p = 0.081). No correlation with any of these parameters was observed in endometrial tumors. In both tumor types, no association of PTEN expression with any other analyzed parameter was found. Conclusions: These results suggest that PTEN expression plays different roles in the pathogenesis of endometrial carcinomas and breast cancer. In mammary carcinomas, loss of PTEN expression is mainly found in more differentiated tumors and is probably not a major event in carcinogenesis.

Dysregulated PTEN‐PKB and negative receptor status in human breast cancer

“…The relationship between dysregulated PTEN-PKB and reduced ER/PR expression in human breast cancers has been reported previously, 21,22 which is corroborated by our data from this current study (Table IV), although contradicted by Kappes et al 25 The precise mechanism behind this observation is not entirely clear. It has been noted by others that increased PKB mRNA correlates with ER-negative breast tumours 56 and increased ER␣ activity, which will lead to tamoxifen resistance.…”

“…We would suggest that the single contradictory study that reported reduced PTEN in association with high ER immunoreactivity might be related to the fact that Western blotting for PTEN protein was conducted with no micro-dissection, so that their result would have included PTEN from both normal and malignant tissues. 25 None of the other molecular markers of p53, p21, PTEN or PKB demonstrated prognostic value in this cohort of 78 patients. ER and PR-negative tumours, however, fared poorly in this otherwise favourable group of LNN breast cancer patients.…”

“…16,21,22 Another report, however, contradicted this observation by associating reduced PTEN with high ER expression. 25 We therefore proceeded to evaluate the PTEN-PKB pathway in primary breast cancer surgical specimens and report that this pathway appears to be dysregulated in approximately 1 ⁄3 of lymph node negative (LNN) patients. In turn, this dysregulation was associated with reduced ER or PR expression, although this does not appear to be a direct causal relationship.…”

Salvianolic acid A positively regulates PTEN protein level and inhibits growth of A549 lung cancer cells

“…At the molecular level, the results of repeated experiments suggested that Sal A treatment significantly increased PTEN protein level and consistently decreased phosphorylation of Akt at S473. PTEN expression is reduced in various tumor types, such as lung and breast cancers (15,16). The regulation of PTEN protein level is highly involved in the cell growth.…”

Somatic mutations are present in all members of the AKT family in endometrial carcinoma

“…Additional mechanisms of PI3 kinase pathway activation in endometrial cancer include the somatic mutation of PTEN and PIK3CA (Kong et al, 1997;Oda et al, 2005), amplification and overexpression of PIK3CA (Miyake et al, 2008;Salvesen et al, 2009), and decreased expression of PTEN (Kanamori et al, 2001;Kappes et al, 2001).…”