Correlation between nuclear grade and biological prognostic variables in invasive breast cancer

Grading of carcinomas is an estimation of differentiation. Nuclear grading is the cytological evaluation of tumor nuclei in comparison with the nuclei of normal mammary epithelial cells. Because nuclear grading does not involve an assessment of the growth pattern of the tumor, it applies not only to invasive ductal carcinoma but also to other subtypes of breast carcinoma.

A total of 215 primary breast carcinomas obtained from the Affiliated Kihoku Hospital of Wakayama Medical College were enrolled in our present study. Nuclear grade was evaluated according to the criteria of the National Surgical Adjuvant Study of Breast Cancer (NSAS-B) protocol. Immunohistochemistry was also performed to determine Bcl-2, p53, c-erbB-2, estrogen receptor (ER) and MIB-1 expression in paraffin-embedded tissues for all cases.

Thirty-two (14.9%) of the patients were graded as 1,124 (57.7%) as 2, and 59 (27.4%) as 3. Nuclear grade displayed a negative correlation with Bcl-2 expression (r=-0.308, p<0.0001), and a positive correlation with c-erbB-2 overexpression (r= 0.172, p=0.0117) and tumor proliferative index labeling by MIB-1 (r=0.485, p<0.0001).

These results imply that nuclear grade is related to the characteristics of tumor biology, indicating that the morphology and biology of breast cancer are tightly linked. Our present results also suggest that adding the nuclear grade to the pathological diagnosis of invasive breast carcinoma may be clinically useful for predicting tumor behavior, for example aggressiveness, and for prognostication.