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

Colakoglu, Tamer; Yildirim, Sedat; Kayaselcuk, Fazilet; Nursal, Tarik Zafer; Ezer, Ali; Noyan, Turgut; Karakayali, Hamdi; Haberal, Mehmet

doi:10.1016/j.amjsurg.2007.05.061

« Previous Next »The American Journal of Surgery
Volume 195, Issue 6 , Pages 719-725, June 2008

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

Tamer Colakoglu, M.D.
- Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
- Corresponding author. Tel.: +90-322-327 27 27; fax: +90-322-327 12 76.
Sedat Yildirim, M.D.
- Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
Fazilet Kayaselcuk, M.D.
- Faculty of Medicine, Department of Pathology, Baskent University, Ankara, Turkey
Tarik Zafer Nursal, M.D.
- Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
Ali Ezer, M.D.
- Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
Turgut Noyan, M.D.
- Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
Hamdi Karakayali, M.D.
- Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
Mehmet Haberal, M.D.
- Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey

Received 13 March 2007; received in revised form 28 May 2007 published online 28 April 2008.

Abstract

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.

Keywords: PTEN expression, pAKT, Colon cancer, Adenomatous polyp