Nonspecific Increased Serum Levels of Secretory Component in Lung Tumors: Relationship to the Gene Expression of the Transmembrane Receptor Form

Polymeric immunoglobulin receptor (pIg-R) is synthesized by epithelial cells lining the bronchial mucosa. It is released in secretions as free secretory component (SC) or bound to Ig as secretory Ig (S-IgA and S-IgM). To evaluate the usefulness of SC and pIg-R expression as tumor markers, we measured SC and secretory Ig, using enzyme-linked immunosorbent assay, in the serum of 45 patients with lung carcinomas, in the serum of 10 patients with non-neoplastic diseases, and in the serum of 45 control subjects. We also studied the immunohistochemical expression of pIg-R and its mRNA in tumors from 20 out of the 45 patients. Serum levels of SC and S-IgA were similarly and significantly elevated in patients with lung cancer (squamous cell carcinoma [25 cases], small cell carcinoma [7 cases], adenocarcinoma [13 cases]) and with non-neoplastic diseases, as compared with control subject levels (P < 0.001). The highest SC levels were found in patients with adenocarcinoma although the mean SC level was not different from other pathologic conditions. pIg-R was usually not detected in the cells of small cell carcinoma or of squamous cell carcinoma, whereas it was found in the cells of five adenocarcinomas and in the two in situ carcinomas under study. The specific mRNA analysis usually agreed with the immunolocalization of pIg-R. A single band at 3.8 kb was detected in the positive tumor tissues and in normal lung tissues. However, the signal was weak in one case of squamous carcinoma and stronger in two out of three adenocarcinomas, than in normal tissues. Seven transplanted tumors, developed in nude mice from the metastases of adenocarcinoma (three cases), small cell carcinoma (one case), and squamous cell carcinoma (three cases), were negative for pIg-R and its mRNA expression. We concluded that high serum levels of SC were not specific for lung tumors and that SC was secreted mainly by normal lung tissue in contact with tumor cells, except in adenocarcinoma where tumor cells synthesized pIg-R. High pIg-R mRNA levels and pIg-R expression could be considered characteristic features of adenocarcinomas. The preserved expression of both pIg-R and its mRNA in cells of in situ squamous cell carcinoma, and expression of a weak expression of the pIg-R RNA only, in some of the squamous cell carcinomas, could indicate intermediate stages of cell differentiation.