Correlation between histologic grade of malignancy and copy number of c-erbB-2 gene in breast carcinoma. A retrospective analysis of 176 cases.

A system of histologic grade of malignancy in human breast carcinoma was devised by significantly modifying the way of evaluating number of mitoses and architectural atypia in the histologic grading of Bloom and Richardson. The modified grading system was applicable to all histologic subtypes of adenocarcinoma and showed a good association with prognosis of breast carcinoma patients in retrospective analysis of 176 consecutive surgical cases (P less than 0.0001). Of the three components of histologic grade, architectural atypia and number of mitotic figures independently had a significant effect on the prognosis. The copy number of c-erbB-2, a prognostic factor independent of tumor size and nodal status, was strongly correlated with the histologic grade, number of mitotic figures, and degree of nuclear atypia (P less than 0.001, each). Cox's regression model analysis showed that nodal status and histologic grade were two determinants of prognosis, and the independent effect of c-erbB-2 amplification was absorbed within that of the histologic grade. Although the importance of c-erbB-2 gene copy number seemed to be inferior to that of the histologic grade, both were shown to be strongly associated with the aggressiveness of the tumor itself rather than the extent of tumor spread.