DIFFERENTIAL EXPRESSION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR AND ITS LIGANDS IN PRIMARY NONSMALL CELL LUNG CANCERS AND ADJACENT BENIGN LUNG

The epidermal growth factor receptor (EGFR) and one of its ligands, tr ansforming growth factor alpha (TGF-alpha), are thought to function as a potential autocrine loop in non-small cell lung cancer (NSCLC). How ever, the expression pattern of EGFR and the TGF-alpha-related ligands have not been fully characterized in primary NSCLC and adjacent benig n lung tissue. For this reason, we comprehensively examined the coexpr ession and differential expression of EGFR and its ligands, TGF-alpha, epidermal growth factor (EGF), and amphiregulin (AR), by Northern ana lysis, in paired samples of primary tumors and uninvolved lung. For th ose RNA species overexpressed in malignant lung, single cell expressio n patterns were studied by immunohistochemistry. Specimens were obtain ed from 57 consecutive patients who underwent resection of carefully s taged resectable NSCLC and were followed prospectively. Most (112 of 1 14) tissue samples yielded high-quality RNA. EGFR was expressed in 82 of 88 (93%) tissue samples, while TGF-alpha was expressed in 62 of 72 (86%) samples, and AR was expressed in 64 of 70 (92%) samples. EGF was unexpressed in total cellular RNA in both tumor and uninvolved lung. In a comparison of RNA expression patterns in tumors and uninvolved lu ng, overexpression of EGFR was found in 45% (22 of 44) of tumors, whil e overexpression of TGF-alpha was seen in 61% (22 of 36) of tumors, an d decreased expression of AR was seen in 63% 122 of 35) of tumors. Cel l type and stage did not influence differential expression, indicating that this is a frequent event in primary NSCLC. Simultaneous overexpr ession of EGFR and TGF-alpha was seen in only 38% of tumors. Simultane ous overexpression of EGFR and decreased expression of AR were seen in only 21% of tumors. Thus far the differential expression of EGFR, TGF -alpha, and AR does not correlate with either disease-free or overall survival. These findings indicate that histologically dissimilar tumor s can express similar components of autocrine or paracrine growth fact or loops. Differential expression of EGFR and its ligands in tumor spe cimens compared to uninvolved lung is a common event in NSCLC and may participate in tumor growth without necessarily influencing tumor prog ression or histology.