CD44v6 expression in primary bronchioloalveolar carcinoma and conventional pulmonary adenocarcinoma

CD44 is a family of transmembrane glycoproteins involved in cell-to-cell and cell-to-matrix interactions. Of the CD44 isoforms characterized, the v6 variant has been shown to confer metastatic potential in animal models and its expression has been correlated with aggressive behavior in some human malignancies. In an attempt to provide further insight into the heterogeneous appearance and behavior of bronchioloalveolar carcinomas (BACs), the pattern of CD44v6 staining in five mucinous, five nonmucinous, and eight sclerosing stage I BACs were compared with 12 comparably staged conventional pulmonary adenocarcinomas (CPAs). Formalin-fixed, paraffin-embedded sections were stained with monoclonal antibodies to CD44v6 (clone VFF-7). Neoplastic goblet cells, whether growing in a lepidic pattern in mucinous BACs or in an invasive pattern in CPAs, consistently demonstrated low level expression of CD44v6. In contrast, lepidic growth by neoplastic cells of type 2 pneumocyte or Clara cell differentiation demonstrated high levels in five of five cases of nonmucinous BACs, seven of eight cases of sclerosing BACs, and six of nine cases of CPAs. Similar cells of type 2 pneumocyte or Clara cell differentiation within the scarred area of sclerosing BAC demonstrated an intermediate degree of staining with four of eight cases marking with high levels, whereas none of the nine cases of CPAs with invasion by these cells showed high levels in the desmoplastic areas. From these results, two patterns of CD44v6 expression were recognized in BACs and CPAs. First, the expression appeared to be partly dependent on differentiation as cells demonstrating mucinous differentiation, whether in BACs or CPAs, consistently lacked CD44v6 staining. Second, in cells of type pneumocyte or Clara cell differentiation the expression was dependent on the growth pattern and their relationship to the stroma. High level expression was noted in neoplastic cells growing in a lepidic pattern, whereas those demonstrating invasion gradually lost the expression with increasing degrees of stromal reaction. Thus, the expression of CD44v6 in pulmonary BACs and similarly staged CPAs appears to be different from other human malignancies that have a positive correlation with aggressive behavior.