Steroid receptors in human lung cancer

Abstract

We have determined that a significant incidence of specific high affinity receptors for androgen (AR), estrogen (ER), and glucocorticoid (GR) is present in normal adult human lung and bronchogenic carcinoma cytosols. In contrast, a limited number of tumor cytosols bound progesterone. Binding characteristics for each class of steroid hormones were similar to those reported for other steroid-responsive normal and neoplastic tissues. ER was evenly distributed between squamous cell and adenocarcinoma cytosols with a slightly lower affinity, but higher content than normal lung. In normal lung, GR resolved into two distinct binding components based on affinity using a dextran-coated charcoal assay. AR in squamous cell carcinomas behaved in a similar manner. This was not observed when hydroxyapatite was used to separate bound from free ligand. When AR affinity and content were stratified on the basis of tumor grade in squamous cell carcinoma, the most undifferentiated tumors had a lower AR content and higher affinity. In contrast, there was no differentiation of AR content or affinity based on tumor grade in adenocarcinoma where AR also did not resolve into two distinct groups based on binding affinity. Although related to tumor grade, AR incidence and content were not related to stage of disease. In adenocarcinoma, initial results suggest GR affinity and content were inversely related to degree of tumor differentiation, while GR content was slightly lower in poorly differentiated squamous cell carcinomas. GR content in squamous cell carcinoma increased slightly between Stages I and II and declined significantly in Stage II patients. This was not observed in adenocarcinoma, where GR content appeared to increase with stage of disease. Our results suggest that a significant incidence of specific, high affinity receptors for estrogen, androgen, and glucocorticoid is present in nonsmall cell carcinomas of the lung, which could provide a useful starting point for examining whether steroids influence the natural history of selected bronchogenic carcinomas.