Prognostic value of broad-spectrum keratin clones AE1/AE3 and CAM5.2 in small cell lung cancer patients undergoing pulmonary resection

  • Andrzej Badzio Centrum Radioterapii NU-MED Elbląg
  • Piotr Czapiewski 1Department of Pathology, Medical University of Gdansk, Poland; 2Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany
  • Adam Gorczyński Department of Pathology, Medical University of Gdansk, Poland
  • Kamila Szczepańska-Michalska Copernicus Hospital, Gdansk, Poland
  • Johannes Haybaeck 1Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany; 2Institute of Pathology, Medical University of Graz, Austria; 3Department of Pathology, Neuropathology and Molecular Pathology, Medical University Innsbruck, Austria
  • Wojciech Biernat Department of Pathology, Medical University of Gdansk, Poland
  • Jacek Jassem Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland


Introduction: Small cell lung carcinoma (SCLC) is an aggressive pulmonary neoplasm of neuroendocrine origin. Keratins form a large group of intermediate filaments, which are major structural proteins in epithelial cells and carcinomas. SCLC shows a wide spectrum of keratin expression, from very strong
to completely negative. A prognostic role of keratin expression in SCLC is unknown. Material and Methods: Tumor tissue microarray samples from a unique series of 82 SCLC patients who underwent pulmonary resection were stained with keratin specific antibodies AE1/AE3
and CAM5.2. The percentage o1f positively stained cells and their staining pattern (diffusely membranous, partially membranous and dot-like) were evaluated. The median expression value was used for the distinction between keratin-negative and -positive patients. Overall survival in respective groups was compared using the log-rank test. Multivariate Cox proportional hazards regression analysis was performed adjusting for age, gender, tumor site, tumor stage, and tumor histology. Results: edian expression of AE1/AE3 and CAM5.2 was 80% and 90%, respectively. Five cases were completely negative for AE1/AE3 and three for Cam5.2. Median overall survival for patients with stronger and weaker AE1/AE3 staining was 24.7 and 13.8 months, respectively (p=0.019).
There was no difference in survival in relation to the CAM5.2 expression (p=0.44). In multivariate analysis adjusted for CAM5.2, T and N stage, gender and age at diagnosis, stronger AE1/AE3 expression was an independent predictor of increased survival (HR 0.50; 95% CI, 0.27–0.94; p=0.031). Conclusion: High expression of AE1/AE3 is a favorable prognostic factor in surgically treated SCLC. The applicability of this finding to a typical patient population treated with non-surgical methods warrants further studies.