CD44 AND ITS V6 SPLICED VARIANT IN LUNG-TUMORS - A ROLE IN HISTOGENESIS

BACKGROUND, CD44 is a polymorphic family of cell surface glycoproteins with a variety of functions including participation in cell adhesion and migration as well as modulation of cell-matrix interactions. Expre ssion of the standard form of CD44 (CD44s) and its variant isoforms ha s been shown in both normal and neoplastic tissue and holds promise as a prognostic indicator. METHODS, The authors investigated the express ion of CD44s and its v6 isoform (CD44v6) immunohistochemically in 7 fe tal lungs (gestational age between 11-36 weeks) and in 80 lung tumors of various histologic types, degrees of differentiation, and clinical stages. RESULTS, In the fetal lung, CD44v6 was expressed as membranous and luminal staining of epithelial cells throughout gestation and bas al staining of bronchial epithelium late in gestation. Nonneoplastic a dult lung showed CD44v6 expression that was restricted to epithelial c ells with membranous staining of basal bronchial cells and squamous me taplasia as well as basolateral membranous staining of type 2 pneumocy tes. CD44s showed similar but less intense staining and was in additio n present on lymphocytes and macrophages. Tumorlets and neuroepithelia l bodies were CD44v6 negative. Nearly all squamous cell carcinomas (97 %) were positive for CD44v6 with patterns similar to squamous metaplas ia and with more intense staining at the periphery of tumor nests. Mos t adenocarcinomas (90%) were CD44v6 negative whereas most bronchioloal veolar cell carcinomas (71%) were CD44v6 positive with patterns simila r to that in type 2 pneumocytes. Most large cell carcinomas (71%), car cinoid tumors (67%), and all small cell carcinomas were CD44v6 negativ e. CD44v6 expression did not correlate with clinical stage. CD44v6 exp ression in lymph node metastases was identical to that of the primary tumor. CONCLUSIONS, The results of the current study show that CD44v6 is localized differently in fetal and adult lung, suggesting a differe nce in function. In the fetal lung, it may modulate growth factors imp ortant in morphogenesis and maturation. In the adult nonneoplastic lun g, CD44v6 is associated with stem cells, namely basal cells and type 2 pneumocytes, and may act to anchor these cells to the matrix and be i mportant in migration during repair or neoplasia. In addition, CD44v6 expression is maintained throughout tumorigenesis in squamous cell car cinoma and bronchioloalveolar cell carcinoma, suggesting a histogeneti c relationship between the stem cells and the respective tumors. Conve rsely, most neuroendocrine tumors and the cells of the dispersive neur oendocrine system do not express CD44v6, implying a separate histogene tic lineage in these rumors. (C) 1997 American Cancer Society.