Paul-Georg Knapstein

Immunohistochemical evaluation of growth fractions in human breast cancers using monoclonal antibody Ki-67

SummaryWe performed immunohistochemical analyses of 568 breast/cancer specimens using Ki-67, a monoclonal antibody specific for a nuclear antigen present in proliferating cells. The specimens were divided into three groups (I–III) according to the proportion of Ki-positive cells detected. These findings were compared with features of tumor extension as well as with certain prognostic variables.There was no detectable correlation between Ki-67 reactivity and either tumor size or node involvement. In contrast, a statistically significant correlation was found between Ki-67 reactivity and tumor grading, in that G-I tumors had small growth fractions, while a high proportion of G-III tumors exhibited strong (group III) Ki-67 positivity. When growth fractions were compared with biochemical receptor status, a significant difference was detected between tumors with negative and positive findings for receptors. The same co-variation was observed with respect to the overexpression ofneu-protein P185, with mostneu-positive carcinomas being strongly positive for Ki-67 (group III).In the relapse cases examined, there was a close correspondence between Ki-67 reactivity and the duration of the disease-free period. Long-term observation of patients with primary breast carcinoma revealed that, with regard to overall survival, the less reactive groups I and II differed significantly from group III. With respect to disease-free survival, no difference was detectable between Ki-groups II and III, but when these two groups together were compared with group I, a significant trend emerged. Similar results for both overall and disease-free survival were obtained for subgroups of pT2 and G-II carcinomas as well as for receptor expression. Node-negative tumors in the highly reactive group III exhibited a strong trend indicating unfavorable overall survival rates, whereas no such difference was demonstrable with respect to disease-free survival. Node-positive tumors could not be differentiated on the basis of overall survival, but the correlation with growth fraction was significant for disease-free survival.In conclusion, Ki-67 offers a simple and effective method for defining the proliferating cell compartment of breast carcinoma, and may facilitate the assessment of individual tumors as well as efforts to predict the course of disease.

C-erbB-2-oncogene expression in breast carcinoma: Analysis by S1 nuclease protection assay and immunohistochemistry in relation to clinical parameters

The c-erbB-2 mRNA was detected by the S1 nuclease protection assay and Northern blotting in breast cancer tissues. In contrast to the Northern blot analysis which has been used in all recent publications concerning c-erbB-2 expression on the level of RNA, the S1-nuclease protection assay has distinct advantages with respect to sensitivity, reproducibility, and handling of radioactive probes. We compared the expression of c-erbB-2 in 120 breast carcinomas which were operated in the years 1989-1990 on the level of the mRNA (S1 nuclease protection assay) and the protein (immunohistochemistry), respectively. In general, results obtained with both methods were in good agreement. Only minor differences in classification were observed with 18 samples, all of them belonging to either the moderate or the weak c-erbB-2 expression phenotype. In addition, the level of c-erbB-2-protein was investigated by immunohistochemistry in 271 breast carcinomas which were operated in the years 1984-1987. Comparison of the level of c-erbB-2 expression with the patient history indicates that patients whose tumors had already metastasized to the axillary nodes showed a reduced overall and disease-free survival in the group with pronounced expression of the c-erbB-2 protein. Thus the strong expression of c-erbB-2 oncogene in primary breast cancers appears to be an additional and particular prognostic factor in lymph node positive patients.