Occurrence and Frequency of Heterogeneity in EGFR Immunohistochemical Expression in Lung Adenocarcinomas of Mixed Type – Possible Consequences for EGFR Predictive Testing
JR Nilsson, C Lindh, S Fanunza, S Ahlberg, G Elmberger. Karolinska Hospital, Stockholm, Sweden
Background: In industrialized countries adenocarcinomas are now the most frequent type of lung cancer. Adenocarcinomas are often morphologically heterogeneous, with a mixed sub-type representing 80%. The evaluation of the epidermal growth factor receptor (EGFR) status is now commonplace, due to targeted therapy. The purpose of this study was to investigate if variation in immunohistochemical (IHC) staining intensity for EGFR correlated with the histomorphological heterogeneity in adenocarcinomas.
Design: 26 surgical specimens from lung neoplasms, diagnosed as primary adenocarcinomas of mixed type, were sub-typed according to their growth pattern (WHO-classification 2003) and evaluated by IHC for EGFR (clone 31G7, ZymedTM, 1:25). The IHC expression of EGFR was scored 0-3 as follows: 0, no staining or faint membrane staining in <10% of the tumour cells; 1+, faint/barely perceptible staining in ≥10%; 2+, weak to moderate staining in ≥10%; 3+, strong membrane staining in ≥10%. Heterogeneity in IHC expression was considered significant when growth patterns displayed a difference in staining intensity score of 2 or more.
Results: All tumours, in varying intensity, stained positively for EGFR. The staining pattern was generally diffuse with a gradual variation in intensity. Abrupt and significant differences in staining intensity were only noticed in areas of transition from one growth pattern to another with an accompanying change in cellular atypia. 5 out of 26 (19 %) adenocarcinomas displayed a significant variation in staining intensity between different growth patterns. In two of these cases an increased expression was shown in the acinar compared to the bronchoalveolar component. In one of these cases the result was confirmed with FISH-analysis, showing a high-grade amplification in the acinar component. Furthermore, an inverse expression pattern was displayed in one case, with decreased staining intensity in the acinar component compared to the bronchoalveolar. In another two cases a decrease in the expression of the solid component was shown compared to the acinar.
Conclusions: This study showed a significant heterogeneity in EGFR IHC expression in 19% of the cases and staining intensity was correlated with variations in growth pattern. This could be of importance when selecting material for EGFR mutation detection, in order to avoid false negative results. Our suggestion is therefore to pre-screen resection material with either IHC or FISH/CISH before mutation analysis.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 256, Tuesday Morning