Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms:: is PTEN loss predictor of local recurrence?

BACKGROUND: PTEN is a tumor-suppressor gene located on chromosome 10. Deficient PTEN expression leads to activation of the phosphoinositide 3-kinase (PI3K)/Akt (pAkt) signaling pathway, which may contribute to multiple human cancers. The relation between PTEN expression and Akt activation is still unclear in colorectal cancers and adenomatous polyps. Moreover, PTEN and pAkt expression in relation to demographic, tumoral, and outcome variables remains to be elucidated. METHODS: PTEN and pAkt expression were evaluated in 76 primary colorectal cancers and 25 adenomatous colorectal polyp tissues using immunohistochemical staining on paraffin-embedded sections. PTEN and pAkt expression were compared with clinicopathologic features of colorectal cancers. The relationship between PTEN and pAkt expression was also investigated. RESULTS: In colorectal cancers, pAkt expression was found to be significantly higher than polyps (P = .007). On the other hand, PTEN expression was significantly lower in polyps (P < .0001). In colorectal cancer patients, PTEN expression showed a negative correlation with young age, female sex, and left-sided (distal) tumors. On multivariate analysis, low PTEN expression (PTEN loss) was noted as an independent parameter for local recurrence (P = .024). There was significant association between pAkt expression and stage (P = .008), and preoperative serum carcinoembryonic antigen (CEA) levels (P = .017) in colorectal cancers. A negative correlation between PTEN and pAkt expression was found in colon cancer patients (P = .010), whereas no significiant association was found in adenomatous polyps (P = .403). No correlation of PTEN expression or pAkt expression was observed in Kaplan-Meier survival statistics and multivariate analyses for disease-free and overall survival. CONCLUSIONS: The current study suggests that the PTEN loss-PI3K/pAkt pathway may play an important role in sporadic colon carcinogenesis and that reduced PTEN expression may predict relapse in colorectal cancer patients. (C) 2008 Elsevier Inc. All rights reserved.