Colakoglu Tamer, Yildirim Sedat, Kayaselcuk Fazilet, Nursal Tarik Zafer, Ezer Ali, Noyan Turgut, Karakayali Hamdi, Haberal Mehmet
Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey.
Am J Surg. 2008 Jun;195(6):719-25. doi: 10.1016/j.amjsurg.2007.05.061. Epub 2008 Apr 28.
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.
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.
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.
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.
PTEN是一种位于10号染色体上的肿瘤抑制基因。PTEN表达缺失会导致磷酸肌醇3激酶（PI3K）/蛋白激酶B（pAkt）信号通路激活，这可能与多种人类癌症的发生有关。在结直肠癌和腺瘤性息肉中，PTEN表达与Akt激活之间的关系仍不清楚。此外，PTEN和pAkt表达与人口统计学、肿瘤及预后变量之间的关系仍有待阐明。
采用免疫组织化学染色法对76例原发性结直肠癌和25例结直肠腺瘤性息肉组织的石蜡包埋切片进行PTEN和pAkt表达评估。将PTEN和pAkt表达与结直肠癌的临床病理特征进行比较。同时也研究了PTEN与pAkt表达之间的关系。
在结直肠癌中，发现pAkt表达显著高于息肉（P = 0.007）。另一方面，息肉中的PTEN表达显著较低（P < 0.0001）。在结直肠癌患者中，PTEN表达与年轻、女性及左侧（远端）肿瘤呈负相关。多因素分析显示，低PTEN表达（PTEN缺失）是局部复发的独立参数（P = 0.024）。在结直肠癌中，pAkt表达与分期（P = 0.008）及术前血清癌胚抗原（CEA）水平（P = 0.017）之间存在显著相关性。在结肠癌患者中发现PTEN与pAkt表达呈负相关（P = 0.010），而在腺瘤性息肉中未发现显著相关性（P = 0.403）。在无病生存期和总生存期的Kaplan-Meier生存统计及多因素分析中，未观察到PTEN表达或pAkt表达的相关性。
本研究表明，PTEN缺失-PI3K/pAkt通路可能在散发性结肠癌发生中起重要作用，且PTEN表达降低可能预测结直肠癌患者的复发。
