Evidence by in situ hybridization that c-erbB-2 proto-oncogene expression is a marker of malignancy and is expressed in lung adenocarcinomas.
In order to identify potential markers of malignancy in diagnostic respiratory cytopathology, c-myc and c-erbB-2 proto-oncogene expression was studied in fine needle aspirates from 14 consecutive fresh operation tissue samples (after surgical removal) representing lung tumors and a variety of other cell samples by in situ hybridization of 35S-labeled antisense and sense RNA c-myc and c-erbB-2 specific proto-oncogene probes. All 14 lung tumors showed c-myc expression and eight also showed c-erbB-2 expression. On average, the c-myc expression was about 4 times higher than that of c-erbB-2 (P less than 0.001). c-erbB-2 expression, confirmed also as a cytoplasmic membrane-bound reactivity by immunohistochemical stainings for c-erbB-2 oncoprotein, was significantly related to adenocarcinoma (P less than 0.025), whereas increasing tumor size correlated significantly with increasing c-myc expression (P less than 0.05). On average, all the tumor cell lines showed 2-fold expression of c-myc compared with the lung tumors (P less than 0.025). c-erbB-2 expression was found in six of 11 cell lines. High c-myc proto-oncogene expression was also found in broncho-epithelial cells and alveolar macrophages, and a low expression was found in lymphocytes but not in neutrophils, while none of these cells showed c-erbB-2 proto-oncogene expression. Our results demonstrate extensive c-myc proto-oncogene expression in both malignant and non-neoplastic proliferating cells, but not in terminally differentiated cells such as neutrophils. Therefore c-myc expression must also be related to general cell proliferation and not only malignancy per se. In marked contrast, c-erbB-2 proto-oncogene expression was found only in adenocarcinoma cells, and thus can be used as a marker for malignancy in diagnostic respiratory cytopathology.
Department of Pathology, University of Oulu, Finland.
P
P
Pääkkö
K
K
Nuorva
D
D
Kamel
Y
Y
Soini
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000367:Age Factors; D000368:Aged; D001707:Biopsy, Needle; D001980:Bronchi / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D016259:Genes, myc; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D009928:Organ Specificity / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D011519:Proto-Oncogenes; D011650:Pulmonary Alveoli / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D012737:Sex Factors; D014407:Tumor Cells, Cultured
D005819:Genetic Markers; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human