PREFERENTIAL HISTIOTYPIC EXPRESSION OF CD44-ISOFORMS IN HUMAN LUNG-CANCER

The CD44 transmembrane glycoprotein is expressed in most adult tissues and in the majority of neoplasias. Due to alternative splicing, this cell adhesion molecule exists in multiple isoforms some of which have been associated with specific types of tumours as well as with increas ed tumour metastasis. In this study, we have looked at the level and t ype of CD44 expression in lung cancer which represents a histologicall y heterogenous form of cancer composed of small cell lung carcinoma (S CLC) and non-small cell lung carcinoma (NSCLC), the latter subgroup co mprising adenocarcinoma (ADC), bronchio-alveolar carcinoma (BAC), larg e cell carcinoma (LCC), and squamous cell carcinoma (SCC). We analysed 20 lung cancer cell lines and 64 primary tumours by RT-PCR and immuno histochemical detection of the CD44 standard and variant protein isofo rms. Our results suggest that (i) CD44 is expressed in all histologica lly distinct subsets of lung cancer with a tendency SCC > BAC > ADC > LCC > SCLC, (ii) expression of the CD44 isoforms v5, v7, v8, and, most notably that of CD44 exon v6, strongly correlates with tumours of squ amous cell and bronchio-alveolar carcinoma origin, tumours which commo nly exhibit a comparatively low metastasizing potential, and (iii) the expression of CD44 isoforms is independent from the tumour size and l ymph node status at surgery, the proliferative status of the tumour ce ll population (Ki67 antigen expression) and the histopathological grad ing (G1 to G3). Only non-differentiated tumours (G4), which were restr icted to SCLC and LCC samples revealed markedly reduced CD44 standard and isoform antigen. In conclusion, our data point to a clear histioty pe-related pattern of CD44 variant expression preferentially that of C D44v6 in SCC and BAC. (C) 1997 Elsevier Science Ireland Ltd.