Barros-Silva J D, Leitão D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, Bento M J, Santos L, Ferreira P, Rêgo S, Brandão C, Carneiro F, Lopes C, Schmitt F, Teixeira M R
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Br J Cancer. 2009 Feb 10;100(3):487-93. doi: 10.1038/sj.bjc.6604885. Epub 2009 Jan 20.
The clinical significance of ERBB2 amplification/overexpression in gastric cancer remains unclear. In this study, we evaluated the ERBB2 status in 463 gastric carcinomas using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), and compared the findings with histopathological characteristics and with disease-specific survival. ERBB2 overexpression (2+ and 3+) and amplification (ratio ERBB2/CEP17 >or= 2) were found in 43 (9.3%) and 38 (8.2%) gastric carcinomas, respectively. Perfect IHC/FISH correlation was found for the 19 cases scored as 0 (all negative by FISH), and also for the 25 cases scored as 3+ (all positive by FISH). One out of six carcinomas scored as 1+ and 12 out of 18 carcinomas scored as 2+ were positive by FISH. ERBB2 amplification was associated with gastric carcinomas of intestinal type (P=0.007) and with an expansive growth pattern (P=0.021). ERBB2 amplification was detected in both histological components of two mixed carcinomas, indicating a common clonal origin. A statistically significant association was found between ERBB2 amplification and worse survival in patients with expansive gastric carcinomas (P=0.011). We conclude that ERBB2 status may have clinical significance in subsets of gastric cancer patients, and that further studies are warranted to evaluate whether patients whose gastric carcinomas present ERBB2 amplification/overexpression may benefit from therapy targeting this surface receptor.
ERBB2基因扩增/过表达在胃癌中的临床意义仍不明确。在本研究中，我们采用免疫组织化学（IHC）和荧光原位杂交（FISH）技术评估了463例胃癌中的ERBB2状态，并将结果与组织病理学特征及疾病特异性生存率进行了比较。分别在43例（9.3%）和38例（8.2%）胃癌中发现了ERBB2过表达（2+和3+）及扩增（ERBB2/CEP17比值≥2）。对于评分为0的19例病例（FISH检测均为阴性）以及评分为3+的25例病例（FISH检测均为阳性），IHC/FISH结果完全一致。6例评分为1+的癌组织中有1例、18例评分为2+的癌组织中有12例FISH检测呈阳性。ERBB2扩增与肠型胃癌（P = 0.007）及膨胀性生长模式（P = 0.021）相关。在2例混合性癌的两种组织学成分中均检测到ERBB2扩增，提示存在共同的克隆起源。在膨胀性生长的胃癌患者中，ERBB2扩增与较差的生存率之间存在统计学显著相关性（P = 0.011）。我们得出结论，ERBB2状态在部分胃癌患者中可能具有临床意义，有必要进一步研究评估胃癌出现ERBB2扩增/过表达的患者是否可能从针对该表面受体的治疗中获益。
