Protein overexpression and gene amplification of c-erb B-2 in pulmonary carcinomas: A comparative immunohistochemical and fluorescence in situ hybridization study

Amplification of the c-er bB-2 gene (located on 17q11.2- 12) is accompanied by overexpression of its cell surface receptor product, p185(ERBB2). In pu lmonary carcinomas, however, there has been disagreement between the report ed frequencies of gene amplification and overexpression. To clarify their r elationship, the correlation between the cellular expression of p185(ERBB2) the level of c-erb B-2 gene amplification was studied. A total of 195 pulm onary carcinomas (182 primary and 13 metastatic) were examined immunohistoc hemically using a polyclonal antibody, which recognizes the internal domain of the human c-erb B-2 protein, and positive tumors were further examined for the gene amplification by dual-color fluorescence in situ hybridization using probes for centromere 17 and 17q11.2-12. By immunohistochemistry, di stinct membrane staining was found in an adenocarcinoma, a large cell carci noma and a metastatic carcinoma from the breast, and cytoplasmic and/or fai nt membranous staining was observed in 23 nonsmall cell lung carcinomas. It was in the two primaries and the metastatic carcinoma that more than 8-fol d amplification of c-erb B-2 was found by fluorescence in situ hybridizatio n. Especially, in the two primary carcinomas, tumor cells had amplified gen es with the signals forming one or two clusters, indicating that the amplif ied gene was present in homogeneously staining regions. Among the 23 tumors , three tumors showed low-level amplification (less than 3-fold), which was differentiated from polysomy 17 found in the other two. In the 30 non-smal l cell lung carcinomas selected at random from 151 with negative immunostai ning, there were five trisomy 17, but no tumors with the gene amplification . This suggests that although c-erb B-2 amplification in pulmonary carcinom a is rare, it occurs in the form of a homogeneously staining region and is thought to control the overexpression of the protein in the cell membrane. New adjuvant therapy using a humanized antibody to the oncoprotein may be b eneficial to patients with these tumors.