Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma

Abstract

Aims: Tumour suppressor phosphatase and tensin homologue (PTEN) is an important negative regulator for the PIP3/Akt signalling pathway that promotes cell proliferation and inhibits apoptosis. Inactivation of PTEN by mutation, deletion and promoter hypermethylation has been demonstrated in a range of cancers. The aim was to investigate whether the loss of nuclear PTEN protein expression correlates with conventional clinicopathological parameters and patient survival.

Methods and results: Immunohistochemistry staining for PTEN was performed on a tissue microarray of 19 samples of normal colonic mucosa, 14 adenomatous polyps, 482 adenocarcinomas and 56 metastatic lymph nodes. All 19 normal colonic mucosa samples (100%) were positive and 12 (85.7%) out of 14 adenomatous polyps were positive for PTEN. However, only 241 (50.0%) of the 482 colorectal adenocarcinomas and 26 (46.4%) of the 56 metastatic lymph nodes were positive for PTEN. Loss of PTEN expression was related to defective mismatch repair protein expression and colonic localization rather than rectal localization. On univariate survival analysis, patients with PTEN- adenocarcinoma revealed a poor overall and disease-free survival (P = 0.030 and P = 0.046, respectively). On multivariate analysis, a significant difference was observed in patients with stage II cancer that was not observed in other stages.

Conclusions: Nuclear PTEN expression gradually decrease during the normal-adenoma-adenocarcinoma-metastasis sequence, which suggests an important role for PTEN in carcinogenesis. Moreover, loss of nuclear PTEN expression was a marker of poor clinical outcome in patients with stage II colorectal cancer.