EGFR and K-ras Mutation Status and Correlations Histological Subtypes in Pulmonary Carcinomas. A Dutch Experience
FB Thunnissen, DW de Jong, DA Heideman, EF Smit, S Burgers, PJ Snijders, J Berkhof, CJ Meijer, PM Nederlof. VU University Medical Center, Amsterdam, Netherlands; The Netherlands Cancer Institute, Amsterdam, Netherlands
Background: Emperical treatment with EGFR antagonists is highly effective in a subset of patients with advanced lung cancer. Subsequently, in these patients EGFR mutations were correlated with histopathological subtyping. Initially an association with bronchioloalveolar subtype and later with papillary subtype was suggested. The aim of this study was to determine the relation between histopathological subtypes of lung cancer and EGFR and K-ras mutation status.
Design: From 350 patients mutation analysis for K-ras / EGFR was performed as requested by pulmonologists, i.e. either because of cancer in non-smoking patient or for treatment stratification for recurrence after first line treatment. Paraffin embedded archive material was used for EGFR and K-ras mutation analysis. Histological classification and subtyping were performed according to the WHO classification (2004) with an additional distinction between micropapillary and papillary carcinoma. Odds ratios [OR] and Chi square p values were calculated .
Results: The archival material of 20 cases was qualitatively insufficient for mutation analysis. In addition, 19 cytology specimens were excluded as well. Mixed histological subtypes occurred to a variable extent. The glandular, bronchioloaveolar and micropapillary pattern were positively correlated (P<0.01). These patterns were inversely correlated with solid type adenocarcinoma and large cel carcinoma (p.<0.01). A dominant papillary pattern was present in 8 cases (2.6%). A dominant micropapillary pattern was seen 40 times.EGFR and K-ras mutations were mutually exclusive and detected in 82 and 57 adenocarcinoma cases, respectively. The presence of glandular subtype was positively related to EGFR mutations (OR 2, p<0.01), whereas a solid pattern was negatively related to EGFR (OR 0.35, p<0.05). A micropapillary pattern was positively related to K-ras mutations (OR 1.9, p =0.02). No significant associations were found for: a bronchioloaveolar subtype and EGFR (OR 1.5, p=0.1); a dominant papillary pattern and EGFR (OR 2.89, p=0.12); and intracellular or glandular mucin (n=12) and K-ras (OR 2.3, p=0.17).
Conclusions: In pulmonary adenocarcinoma a combination of glandular, bronchioloaveolar and micropapillary subtype was frequently observed. The glandular subtype was related to EGFR and the micropapillary subtype to K-ras mutations.
Monday, March 9, 2009 9:00 AM
Platform Session: Section F, Monday Morning