HER2 Protein Overexpression and Gene Amplification in Colorectal Adenocarcinomas
Yu Sun, Lixin Zhou, Dengfeng Cao. Peking University Cancer Hospital, Beijing, China
Background: HER2 serves as a prototype of targeted therapy in which Trastuzumab, a human monoclonal antibody, is used to treat breast and gastric carcinomas with HER2 protein overexpression and gene amplification. Colorectal adenocarcinoma (CRC) is one of the leading causes in the world, but there is little data on HER2 protein overexpression/gene amplification in CRCs. Here we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs. We determined the concordance rate between HER2 protein overexpression determined by immunohistochemical staining (IHC) and HER2 gene amplification determined by Fluorescence in situ hybridization (FISH).
Design: 1197 consecutive surgically resected CRCs between 2009 and 2012 were included. One representative paraffin block from each case was used for HER2 IHC staining with a rabbit monoclonal antibody (Clone 4B5, prediluted, Ventana PATHWAY) and FISH study using the PathVysion HER2 DNA probe kit (Vysis/Abbott, Abbott Park, Illinois). The IHC staining was scored: 0 (no staining or membranous staining in less than 10% tumor cells), 1+ (faint/barely visible membraneous staining in at least 10% cells or staining in part of their membrane), 2+ (weak to moderate complete or basolateral membraneous staining in at least 10% tumor cells), 3+ (strong complete or basolateral membraneous staining in at least 10% tumor cells). The total numbers of HER2 and CEP17 signals were counted in at least 20 tumor cell nuclei in 2 different areas. The criteria for HER2 gene expression was defined as HER2 to CEP17 signal ratio at 2.0 or higher or presence of tight gene clusters.
Results: HER2 IHC score 3+, 2+, 1+ and 0 was seen in 31 (2.6%), 104 (8.7%), 477 (39.8%) and 585 (48.9%) tumors, respectively. Among the tumors with IHC 3+ and 2+ scores, the mean tumor cells with positive IHC staining was 90% (median 100%, range 40-100%) and 67% (median 75%, range 5-95%), respectively (p < 0.05). HER2 gene amplification was seen in 24/29 (83%, unreadable in 2/31) tumors with IHC 3+, 5/25 (20%, unreadable in 2/27) tumors with IHC 2+, and 0 (0/10) tumors with IHC 1+ score. Among tumors with IHC 2+ score, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining (N=5, mean 93%, median 95%, range 90-95%) than those without (N=20, median 50%, range 5-95%) (p <0.05).
Conclusions: HER2 overexpression (IHC score 2+ and 3+) is seen in a small percentage of colorectal adenocarcinomas. HER2 gene amplification occurs in the vast majority of tumors with 3+ IHC score but in a much lower percentage of tumors with 2+ IHC score.
Monday, March 4, 2013 1:00 PM
Poster Session II # 128, Monday Afternoon