CD44 and its v6 spliced variant in lung carcinomas: Relation to NCAM, CEA,EMA and UP1 and prognostic significance

CD44 is a polymorphic family of cell surface glycoproteins that was recentl y reported to have important role in cell adhesion and migration as well as modulation of cell-matrix interactions. Thus, expression of CD44 has been proposed to be associated with malignant behavior of tumors like invasive g rowth and formation of metastasis. The expression of CD44s and its v6 isofo rm (CD44v6) was determined immunohistochemically in 106 lung tumors of vari ous histaphenotypes, degrees of differentiation, and clinical stages. The r esults were compared with the expression of NCAM, CEA, EMA and UP1 and with clinicopathological parameters including patients' survival. CD44s was exp ressed in all histophenotypes of non-small cell lung carcinomas (NSCLC) wit h tendency being squamous cell lung carcinoma (SqCC) > bronchioloalveolar a denocarcinoma (BAC) > conventional adenocarcinoma (ConAC) (91, 66.7 and 38. 9%, respectively). Almost identical distribution of positivity revealed CD4 4v6 in all three subgroups of NSCLC mentioned above (91, 66.7 and 36.1%, re spectively). In the subgroup of neuroendocrine tumors, CD44s and CD44v6 wer e restrictedly expressed in smalt cell lung carcinomas (2/14 tumors), while all 3 typical carcinoids were strongly positive for these markers. Express ion of NCAM and CEA was significantly higher in adenocarcinoma subgroup tha n those in SqCC subgroup (45.7 and 75% vs. 14.8 and 39%, respectively). NCA M expression was also significantly different in BACs and in ConACs (69.2 v s. 36.4%, p < 0.05). The expression of CD44 was related to the differentiat ion of SqCC. The carcinomas with keratinization were CD44 positive. Adenoca rcinomas producing mucin were CD44 negative The expression of CD44, NCAM, C EA, EMA and UP I did not correlate with lymph node metastasis and disease s tage. CD44V6 was the only marker that its expression was closely related to patients' survival. The absence CD44v6 but not CD44s in NSCLC group was as sociated with significantly longer survival of patients compared to patient s with CD44v6 positive tumors. This difference was even higher in tumors ne gative for CD44v6 and simultaneously NCAM and/or CEA positive. The data of this study suggest that CD44v6 might be an independent prognostic factor in NSCLC. Moreover, our data give another evidence of diverse role of CD44 in the differentiation and progression of non-small cell lung carcinomas and neuroendocrine carcinomas of the lung.