AMPLIFICATION AND EXPRESSION OF THE C-ERBB-2 ONCOGENE IN NORMAL, HYPERPLASTIC, AND MALIGNANT ENDOMETRIA

Using differential polymerase chain reaction (DPCR), dot blot hybridiz ation, and an immunohistochemical technique, we determined the amplifi cation and expression of the c-erbB-2 oncogene in 25 normal, 31 hyperp lastic, and 72 malignant samples of the endometrium in 128 patients. U sing DPCR, we found amplified c-erbB-2 (two to 12 copies) in two of 25 (8%) normal, 15 of 31 (48%) hyperplastic, and 45 of 72 (63%) malignan t samples. These results were closely correlated with those from dot b lot (r = 0.78). When comparing the results of DPCR with those of the i mmunohistochemical method, we noted that the negative findings coincid ed with one another, i.e., nonamplification was associated with the ab sence of immunoreactivity. Further analysis showed that amplified c-er bB-2 was found significantly more in complex and atypical hyperplasias versus simple hyperplasias. This indicates that c-erbB-2 may play a p otential role in the early development of some endometrial carcinomas. Although no correlation was seen between c-erbB-2 amplification and o verall survival in our patients, high-level c-erbB-2 amplification (at least five copies) was significantly associated with the histological grade of endometrial carcinoma and vascular or lymphatic invasion. It is possible that high-level c-erbB-2 amplification identifies a subse t of aggressive endometrial carcinoma that involves vascular or lympha tic invasiveness and poor cell differentiation.