Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients

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 >= 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.