Taniyama K, Goodison S, Ito R, Bookstein R, Miyoshi N, Tahara E, Tarin D, Urquidi V
Department of Clinical Pathology, Kure Kyosai Hospital, Kure, Japan.
J Pathol. 2001 Jul;194(3):341-8. doi: 10.1002/path.908.
Loss of PTEN (phosphatase and tensin homologue deleted from chromosome 10) function has been implicated in the progression of several types of cancer. Allele loss close to the PTEN locus occurs in sporadic colon cancer and germline PTEN mutations cause Cowden disease, an inherited cancer syndrome characterized by an increased incidence of gastrointestinal tract lesions that can progress to colorectal carcinoma. However, although PTEN is a good candidate for involvement in the pathogenesis of sporadic colon cancer, previous analyses have not revealed a high frequency of somatic mutations in colorectal tumours. Alternative mechanisms which could lead to a loss of PTEN expression in colon cancer have not been investigated. This study monitored PTEN mRNA and protein levels in a panel of 50 tumour tissues obtained from 35 patients with sporadic colon cancer. RT-PCR and immunohistochemistry were used to evaluate the expression of mRNA and protein, respectively, in normal, adenoma and adenocarcinoma colorectal tissues as well as in metastatic lesions. To overcome the problem of heterogeneity and normal stromal cell contamination in homogenized tissue specimens, specific cell types were isolated by microdissection prior to PCR analysis. No loss of PTEN expression was evident in any of the colon tissues examined. PTEN protein was localized exclusively in the cytoplasm of normal and tumour cells and no correlation of immunostaining intensity and tumour stage or grade was revealed. As with previous deletion and mutation analyses, the present study suggests that loss of PTEN expression is not prevalent in sporadic colon cancer.
第10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）功能丧失与多种癌症的进展有关。散发性结肠癌中靠近PTEN基因座的等位基因缺失发生，而种系PTEN突变会导致考登病，这是一种遗传癌症综合征，其特征是胃肠道病变的发生率增加，这些病变可能发展为结直肠癌。然而，尽管PTEN是散发性结肠癌发病机制中的一个良好候选因素，但先前的分析并未揭示结直肠肿瘤中体细胞突变的高频率。尚未研究可能导致结肠癌中PTEN表达缺失的其他机制。本研究监测了从35例散发性结肠癌患者获得的50个肿瘤组织样本中的PTEN mRNA和蛋白水平。分别使用逆转录聚合酶链反应（RT-PCR）和免疫组织化学来评估正常、腺瘤和腺癌结直肠组织以及转移灶中mRNA和蛋白的表达。为了克服匀浆组织样本中的异质性和正常基质细胞污染问题，在PCR分析之前通过显微切割分离特定细胞类型。在所检查的任何结肠组织中均未发现PTEN表达缺失。PTEN蛋白仅定位于正常细胞和肿瘤细胞的细胞质中，并且未发现免疫染色强度与肿瘤分期或分级之间存在相关性。与先前的缺失和突变分析一样，本研究表明PTEN表达缺失在散发性结肠癌中并不普遍。
