Department of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Yamagata, Japan.
J Thorac Oncol. 2012 Oct;7(10):1513-21. doi: 10.1097/JTO.0b013e3182641d4f.
Phosphatase and tensin homolog (PTEN) has been established as a tumor suppressor gene with an important role in regulating the phosphatidylinositol-3-kinase/AKT antiapoptotic and survival pathway. The prognostic role of PTEN in non-small-cell lung carcinoma has not been evaluated completely in the context of other molecular information.
Tissue microarrays containing 152 resected non-small-cell lung cancer specimens were used to investigate PTEN and p53 by immunohistochemistry and PTEN by fluorescence in situ hybridization. DNA was isolated and subjected to mutational profiling using the Sequenom Oncocarta v1.0 panel. Clinicopathological features were correlated with PTEN expression, gene copy number, and mutation status.
PTEN staining was absent in 63 (41.4%) of the cases. Significantly more squamous cell carcinomas compared with adenocarcinomas demonstrated loss of (negative) PTEN staining (26 of 44 [59%] versus 32 of 94 [34%]; p = 0.009). PTEN gene copy deletion was present in only seven of 124 evaluable cases (5.6%); all deleted cases were immunohistochemistry negative. In univariate and multivariate (MV) analyses adjusted for sex, age, histology, and stage, loss of PTEN protein expression was associated with significantly shorter disease-free survival (MV hazard ratio: 1.78, 95% confidence interval: 1.01-3.14, p = 0.048), whereas no significant associations were seen with p53 or KRAS and epidermal growth factor receptor (EGFR) mutation status. Importantly, the prognostic value of absent PTEN staining was limited to adenocarcinomas, with MV disease-free survival hazard ratio of 2.68 (95% confidence interval: 1.35-5.32, p = 0.005), whereas no such association was seen in squamous cell carcinomas.
Absence of PTEN protein expression is an independent prognostic marker in early-stage resected lung adenocarcinoma.
磷酸酶与张力蛋白同源物（PTEN）已被确定为一种肿瘤抑制基因，在调节磷脂酰肌醇-3-激酶/AKT 抗凋亡和存活途径方面具有重要作用。在其他分子信息的背景下，PTEN 在非小细胞肺癌中的预后作用尚未得到完全评估。
使用包含 152 例切除的非小细胞肺癌标本的组织微阵列，通过免疫组织化学和荧光原位杂交法研究 PTEN 和 p53，分离 DNA 并使用 Sequenom Oncocarta v1.0 面板进行突变分析。临床病理特征与 PTEN 表达、基因拷贝数和突变状态相关。
在 152 例可评估病例中，有 63 例（41.4%）的 PTEN 染色缺失。与腺癌相比，鳞状细胞癌中明显更多的病例表现出 PTEN 缺失（44 例中的 26 例[59%]与 94 例中的 32 例[34%]；p = 0.009）。在 124 例可评估病例中，只有 7 例存在 PTEN 基因拷贝缺失（5.6%）；所有缺失病例的免疫组化均为阴性。在单变量和多变量（MV）分析中，根据性别、年龄、组织学和分期进行调整，PTEN 蛋白表达缺失与疾病无进展生存期显著缩短相关（MV 危险比：1.78，95%置信区间：1.01-3.14，p = 0.048），而与 p53 或 KRAS 和表皮生长因子受体（EGFR）突变状态无显著关联。重要的是，PTEN 染色缺失的预后价值仅限于腺癌，MV 无进展生存期危险比为 2.68（95%置信区间：1.35-5.32，p = 0.005），而在鳞状细胞癌中则没有这种关联。
在早期切除的肺腺癌中，PTEN 蛋白表达缺失是一个独立的预后标志物。
