Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival

Hirozumi Sawai,Hitoshi Funahashi,Takehiro Wakasugi,Jiachi Ma,Yoichi Matsuo,Akira Yasuda,Hiromitsu Takeyama,Mikinori Sato,Nobuo Ochi,Hiroki Takahashi

doi:10.1186/1471-230x-8-56

Hirozumi Sawai, Hitoshi Funahashi + Show 8 more

Open Access

https://doi.org/10.1186/1471-230x-8-56

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Journal: BMC gastroenterology	Publication Date: Nov 26, 2008
Citations: 156	License type: cc-by

Affiliation: Nagoya City University

Abstract

BackgroundThe tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases.MethodsSixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls.ResultsPTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012).ConclusionOur results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients.

Highlights

The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling
The tumour suppressor phosphatase and tensin homolog (PTEN) is a critical negative regulator of the cell-survival signaling pathway initiated by phosphatidylinositol 3kinase (PI3K) [5,6,7,8,9]
Among colorectal cancer patients with liver metastases, we found that weak PTEN expression was significantly associated with advanced TNM stage and lymph node metastasis

Summary

Introduction

The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. Colorectal cancer is the fourth most common malignancy and the second leading cause of cancer death in Western countries, with liver metastases being the primary cause of death in most patients [1]. The tumour suppressor phosphatase and tensin homolog (PTEN) is a critical negative regulator of the cell-survival signaling pathway initiated by phosphatidylinositol 3kinase (PI3K) [5,6,7,8,9]. The PI3K-PTEN pathway promotes cell survival and proliferation, increases in cell size, and chemoresistance. Each of these biological outcomes results from the interaction of this pathway with other signaling networks. Loss of PTEN expression has been reported to be strongly associated with aggressive tumour features [10,11,12,13]

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