OSTEOPONTIN EXPRESSION IN LUNG-CANCER

Osteopontin (OPN), an integrin-binding, transformation-associated prot ein, is secreted by tumor cell lines in culture and is associated with increased malignancy in some experimental tumor systems. Little is kn own, however, about the significance of OPN expression in human cancer s. The aims of this study were to determine if OPN was expressed in a series of surgically resected lung cancers, and if there was a relatio nship between OPN expression and clinico-pathologic findings or outcom e. Twenty-five patients who underwent curative pulmonary resection wer e studied prospectively. RNA was extracted from primary tumor and dist ant normal lung tissue for each patient. OPN RNA levels were evaluated by northern blotting. Immunohistochemistry on paraffin-embedded tissu e, using an anti-OPN monoclonal antibody, was performed to assess tiss ue distribution of OPN protein. OPN RNA and protein were over-expresse d in the majority of tumors, relative to paired normal tissue. There w as variation in the cells of the tumor that were OPN-immunopositive. I n some cases OPN was present in tumor cells, while in the majority of cases OPN was detected primarily in tumor-infiltrating macrophages and necrotic areas. Over-expression of OPN RNA or protein generally was n ot related to clinico-pathological findings. However, there was a stat istically significant association between OPN-immunopositivity in the tumor and patient survival. These findings suggest that OPN levels in lung tumors have the potential to provide clinically important predict ive information on patient outcome, and that OPN may play a role in th e biology of lung cancer.