DNA grading of malignancy in breast cancer. Prognostic validity, reproducibility and comparison with other classifications.

The prognostic significance of the "DNA malignancy grade" (DNA-MG) was tested in a series of 104 breast cancer patients in comparison with TNM staging, histomorphologic grading according to Bloom and Richardson, mean nuclear area (MNA) and DNA-histogram classification according to Auer. The reproducibility and representativity of the grading systems were investigated, and their results in primary tumors and lymph node metastases were compared. The scalar DNA-MG was assessed on monolayer smears prepared from paraffin-embedded tissues; the smears were automatically Feulgen stained and used for rapid interactive DNA cytometric evaluation by an automated microscope and a TV image-analysis system. TNM staging showed the highest correlation with survival, followed by histomorphologic grading and DNA-MG; MNA and the DNA-histogram classification failed to give statistically significant prognostic information. Both histomorphologic grading and DNA-MG were identified as parameters adding independent prognostic information to the TNM staging. However, only DNA-MG demonstrated an acceptable reliability, with small 95% ranges between repeated measurements within the primary tumor (+/- 0.3 DNA-MG) and a strong correlation between the results in the primary tumor and its lymph node metastases. These findings show that the DNA-MG is a valid and reliable prognostic index that adds significant prognostic information to TNM staging.