Kanagawa Cancer Center Hospital, Japan.
Ann Diagn Pathol. 2010 Feb;14(1):23-9. doi: 10.1016/j.anndiagpath.2009.10.003.
This study was conducted to clarify whether or not expressions of hypoxia-related molecules would have clinicopathological significance in squamous cell carcinoma (SCC) of the esophagus. Expressions of hypoxia inducible factor-1 alpha (HIF-1alpha), glucose transporter 1 (GLUT-1) and RAC-1 were immunohistochemically analyzed in 96 surgically resected SCCs at pT1b (sm1, 12 cases; sm2, 35 cases; sm3, 49 cases). They were divided into a lymph node metastasis (LNM)-positive group composed of 44 cases and an LNM-negative group composed of 52 cases. Immunohistochemical profiles were estimated based on the staining extent (score: 1+, 2+, 3+) and intensity (score: 1+, 2+, 3+). A significant expression pattern was found in the nucleus for HIF-1alpha, cell membrane for GLUT-1 and cytoplasm for RAC-1. The cases were categorized into a high score group (total score of 4 or more) and a low score group (total score of 3 or less) in each maker, respectively. A comparison made between the LNM-positive group and the LNM-negative group showed that the proportion of cases with a high score was larger in the LNM-positive group than in the LNM-negative group (HIF-1alpha, P = .02; GLUT-1, P = .008; RAC-1, P = .001). Among them, HIF-1alpha was found to be significantly related to the disease-free survival (P = .019) and overall survival (P = .034) as well as LNM (disease-free survival, P = .030; overall survival, P = .030). The multivariate analysis demonstrated that the HIF-1alpha expression would be an independent indicator for prognosis. In the superficial SCCs of the esophagus, GLUT-1 and RAC-1 may be involved in LNM, and HIF-1alpha overexpression is expected to predict an unfavorable clinical outcome.
本研究旨在阐明缺氧相关分子的表达是否具有食管鳞状细胞癌（SCC）的临床病理意义。对 96 例手术切除的 pT1b 期 SCC（sm1，12 例；sm2，35 例；sm3，49 例）中缺氧诱导因子-1α（HIF-1α）、葡萄糖转运蛋白 1（GLUT-1）和 Rac-1 的表达进行了免疫组织化学分析。根据染色程度（评分：1+、2+、3+）和强度（评分：1+、2+、3+）将其分为淋巴结转移（LNM）阳性组（44 例）和 LNM 阴性组（52 例）。免疫组织化学图谱基于每个标志物的细胞核 HIF-1α、细胞膜 GLUT-1 和细胞质 Rac-1 的染色程度（评分：1+、2+、3+）和强度（评分：1+、2+、3+）进行评估。在每个标志物中，将病例分为高分组（总分为 4 分或更高）和低分组（总分为 3 分或更低）。LNM 阳性组与 LNM 阴性组比较，HIF-1α（P=.02）、GLUT-1（P=.008）和 RAC-1（P=.001）的高分病例比例较高。其中，HIF-1α与无病生存率（P=.019）和总生存率（P=.034）以及 LNM（无病生存率，P=.030；总生存率，P=.030）显著相关。多因素分析表明，HIF-1α表达是预后的独立指标。在食管浅表 SCC 中，GLUT-1 和 RAC-1 可能参与 LNM，HIF-1α过表达有望预测不利的临床结局。
