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

Abstract

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. The prognostic role of keratin expression in SCLC is unknown.Material and MethodsTumor 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 of 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 Median 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).ConclusionHigh 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.

The roles of M30 and M65 in the assessment of treatment response and prognosis in patients with non-small cell lung cancer, who receive neoadjuvant treatment

“…These re-sults give rise to the thought that M30 and M65 levels do not provide sufficient data to evaluate treatment response in lung cancer. On the other hand, Badzio et al found that high expression of keratin-specific antibodies AE1/AE3 is a favourable prognostic factor in surgically treated small cell lung cancer [21]. Due to our data being the first in patients with lung cancer, who received neoadjuvant treatment, there is a need for further studies in which tumours with different treatment responses are considered, and in creating different responses to chemotherapy [22].…”

Resected cytokeratin-negative small cell lung carcinoma

“…Almost all SCLCs show positivity for keratins, especially low molecular weight keratins 2 5–7. Lack of cytokeratin expression in a resection specimen is an extremely rare phenomenon; however, it has been reported 8 19…”

“…The expression of these immunohistochemical markers has been found to have prognostic significance. For example, in surgically resected SCLC, high expression of AE1/AE3 has been reported to demonstrate favourable prognosis 19. SCLC without apparent neuroendocrine phenotype marker expression has a good prognosis, whereas low INSM1 expression was found to be associated with better prognosis 13…”

Conjunctival epithelial hyperplasia in a patient with a nodular lesion in the palpebral conjunctiva: A case report

“…AE1/AE3 antibody is a CK cocktail, referred to as a 'pancytokeratin'. It detects both high (CK1-6, 10, 14, 15 and 16) and low (CK7, 8, and 19) molecular weight keratins (9). CK5/6 (high molecular weight keratins) antibody detects stratified and transitional epithelium, proliferating squamous epithelium and mesothelial cells.…”