Isoform expression of CD44 adhesion molecules, Bcl-2. p53 and Ki-67 proteins in lung cancer

CD44, belongs to the cell adhesion molecule family and is expressed on cell surfaces in several isoforms which are generated by alternative splicing o f messenger RNA. These splice variants have been shown in several cancer ce ll types and are thought to be involved in tumor progression. The aim of th e current study was to evaluate the expression of selected CD44 variants on lung cancer cells of various histology and to compare these with other mar kers of tumor spread. Surgical samples of primary lung carcinoma of various histology were subjected to alkaline phosphatase-anti-alkaline phosphatase complex immunohistochemistry using a panel of monoclonal anti bodies: anti -CD44 v5, v6, v7/8, v10, anti-Ki-67, anti-Bcl-2 and anti-p53. Positive cell s were scored in a semiquantitative way. The patients were subdivided into groups with and without metastases, as found during surgery. All CD44 varia nts tested could be demonstrated on lung cancer cells, but the incidence of particular isoforms led, depending on lung cancer histology. In general, C D44 expression was highest in squamous cell tumors and lowest in anaplastic small cell carcinomas. Squamous cell cancers had high expression of v5 and v6 variants, while in anaplastic large cell and small cell carcinomas v10 was abundant. When Ki-67, Bcl-2 and p53 protein expression was compared to the incidence of CD44 variants, coincidence was found for v10 only. Most of the cases positive for v10 were also Ki-67 positive (p = 0.0146). In 12 ca ses with metastases, tumor cells had high v6 and Ki-67 expression, but thes e data were not significant compared to cases without metastases. Overall, these data suggest that v5 and v6 variants are of significance in squamous cell lung carcinoma, presumably in the promotion of metastasis, while in an aplastic small cell or large cell cancers only v10 expression seems to corr elate with proteins associated with tumor growth and progression. Copyright (C) 2000 S. Karger AG, Basel.