HER2 Overexpression in Primary and Metastatic Carcinomas in pT2b Gastric Adenocarcinoma: Comparison of Antibodies A4085 and CB11 with Correlation to Results of Fluorescent In Situ Hybridization
JY Kim, KM Park, EY Cho, KM Kim, CK Park. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Inje University Sanggye-Paik Hospital, Seoul, Korea; Chungnam National University Hospital, Daejeon, Korea
Background: Recently a phase III trial has shown a significant improvement in overall survival when trastuzumab is added in patients with HER2+ advanced gastric cancer. However, a limited numbers of HER2 overexpression and/or gene amplification in gastric carcinoma (GC) have been reported and comparison of different anti-HER2 antibodies in primary and paired metastatic GCs has not been conducted.
Design: For this purpose, quadruplicated TMAs from the primary tumor obtained from surgically removed 193 pT2b gastric cancer patients (pN0 in 96 and pN2 in 97 cases), and matching duplicated TMAs from metastatic lymph nodes were used. Immunohistochemistry (IHC) with A4085 (HercepTestTM, Dako) and CB11 (1:400, Novocastra) were performed and compared with fluorescence in situ hybridization (FISH) (Vysis Inc). Three pathologists blinded to FISH results independently interpreted tumor cell membranous staining on a scale of 0 to +3.
Results: The sensitivities and specificities of IHC compared with FISH are as follows: A4085,85.7/95.7 (primary) and 92.3/96.1 (metastatic); CB11, 57.1/99.4 (primary) and 84.6/100 (metastatic). With A4085, 4 (2.6%) of 155 GC cases negative by IHC showed HER2 amplification by FISH, whereas 27 (71.1%) of 38 cases with HER2 protein overexpression showed HER2 amplification by FISH. With CB11, 12 (6.9%) of 175 GC cases negative by IHC showed HER2 amplification by FISH, whereas 1 (5.9%) of 17 cases with HER2 protein overexpression showed HER2 amplification by FISH. Significant concordance between IHC and FISH was observed with A4085 than CB11 (p<0.00). Discrepancies in HER2 status between primary tumors and metastases were observed in 25 cases (13%) by IHC and 20 cases by FISH. Patients with HER2 overexpression by IHC showed significantly worse overall survival [relative risk: 0.706 (95% CI, 0.317-0.375), p = 0.01], whereas it was not statistically significant in patients with HER2 amplification by FISH (log-rank test, p=0.32).
Conclusions: Unlike in breast carcinoma, A4085 predicts HER2 gene amplification with great sensitivity in GC than CB11. Discrepancies in HER2 status between primary tumors and metastases were also observed in GCs. Furthermore, we found that HER2 overexpression may serve as a significant prognostic factor in patients with T2b GC.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 94, Monday Morning