EXPRESSION OF THE ONCOGENE C-ERBB-2 IN CANINE MAMMARY CANCERS AND TUMOR-DERIVED CELL-LINES

Objective-To determine, for canine mammary tumors, whether malignancy, with or without local invasion or regional metastasis, was associated with overexpression of the oncogene c-erbB-2. Design-c-erbB-2 express ion was measured in canine mammary tumor-derived cell lines and in mam mary tumor tissues from clinical cases. Clinical samples were examined histologically to determine whether they were benign or malignant and , if malignant, whether they had evidence of local invasion or regiona l metastasis. Canine fibroblast cultures and normal canine mammary epi thelial tissues were used as reference standards for cell lines and ma mmary tumors, respectively. Sample Populations-28 canine mammary tumor tissue samples obtained surgically from clinical cases and samples fr om 7 canine mammary tumor cell lines derived from primary canine mamma ry tumors. Procedure-c-erbB-2 mRNA levels were determined by means of hybridization of total polysomal RNA with a P-32-labeled human c-erbB- 2 probe on dot blots, and results were quantified by means of scanning densitometry. Overexpression of c-erbB-2 was defined as an autoradiog raphic density greater than or equal to 2 times the density of referen ce samples on the same blot, Results-Overexpression of c-erbB-2 was de tected in 17 of 23 malignant tumors, 0 of 5 benign tumors, and 2 of 7 mammary tumor cell lines. c-erbB-2 overexpression was correlated with a histopathologic diagnosis of malignancy (P = 0.005) but not with the presence of local invasion or regional metastatic disease (P = 0.621) . Conclusions-Results suggest that overexpression of c-erbB-2 occurs p rior to the development of metastatic disease in canine mammary tumors and plays a role in the development of malignancy.