CD44, a cell adhesion molecule, has been implicated in tumor invasion and 
metastasis in certain malignancies. We studied the expression of CD44 standard 
(CD44s) and variant isoforms (CD44v) in 98 non-small cell lung carcinomas 
(NSCLCs) by immunohistochemistry and correlated the observations with clinical 
outcome. Formalin-fixed, paraffin-embedded archival tissues from 49 squamous 
cell carcinomas (SCCs) and 49 adenocarcinomas (ACs) were immunostained after 
microwave irradiation with monoclonal antibodies against CD44s and CD44v3, v4/5, 
v6, v7/8, and v10, and the results were correlated with histological tumor type, 
tumor stage, recurrence, and survival rates. SCCs of the lung showed strong 
membranous expression of each of the CD44s, v3, v4/5, v6, and v10 proteins in 
comparison with ACs (P < .0001). Staining for CD44 v4/5 was overwhelmingly 
positive in SCCs (72%) as compared with ACs (2.2%). Intense immunoreactivity for 
CD44v6 was present in 19 of 20 (95%) metastatic lung carcinomas. The bronchiolar 
basal cells and alveolar pneumocytes were positive for CD44s, v3, and v6. CD44s 
and variant isoform expression did not correlate with tumor stage, recurrence, 
and survival rates. In conclusion, there is significant immunopositivity of 
CD44s and variant isoforms in SCCs over ACs of the lung. Expression of CD44v6 
may suggest an increased risk for local lymph node metastasis in NSCLCs. 
CD44v4/5 reactivity may be useful to discriminate squamoid differentiation in 
poorly differentiated NSCLCs.