HER-2 AMPLIFICATION BUT NOT BUTYRYLCHOLINESTERASE MUTABILITY REFLECTSAGGRESSIVENESS OF EUROPEAN-ORIGINATED OVARIAN-TUMORS

Tumorigenic roles were variably suggested for HER-2 and INT-2 oncogene amplifications and the ''atypical'' aspartate to glycine mutability i n the butyrylcholinesterase (BCHE) gene in ovarian adenocarcinomas. To examine this notion we searched for correlations between these three phenomena and ovarian tumor classification and aggressiveness, using q uantitative polymerase chain reaction (PCR), single-strand conformatio n polymorphism (SSCP), and direct PCR sequencing. Our findings reveale d no alleles carrying the atypical BCHE mutability in 30 European-orig inated patients with ovarian tumors compared with 11% (2/18) such alle les in Israeli patients with malignant ovarian tumors. This apparently reflected population diversity rather than disease relationship. INT- 2 amplification was observed in 14/94 (15%) of the European patients; however, there was no correlation between this phenomenon and clinicop athological indices in the corresponding patients. In contrast, in 94 tumor samples we found that 40% (38/94) of the cases had HER-2 amplifi cation. Moreover, there was a highly significant correlation (P < 0.00 8) between the over fivefold HER-2 amplification and ovarian tumor sev erity. These findings demonstrate an informative value for HER-2 ampli fication tests in tumor DNA, but not for INT-2 amplification or BCHE m utability, for the assessment of treatment. (C) 1995 Academic Press, I nc.