DUCTAL CARCINOMA IRI SITU OF THE BREAST - A PROPOSAL FOR A NEW SIMPLIFIED HISTOLOGICAL CLASSIFICATION ASSOCIATION BETWEEN CELLULAR PROLIFERATION AND C-ERBB-2 PROTEIN EXPRESSION

The diagnosis of ductal carcinoma in situ of the breast (DCIS) has bec ome common with the advent of breast screening programs. Methods: Prol iferation indices (S-phase fraction) were studied in 76 cases of pure DCIS. Tumors were classified according to conventional criteria and al so according to a novel simplified classification based on cellular ne crosis and morphology. This new classification defines three distinct tumor groups: pure comedo in 19 (25.0%) cases, DCIS with necrosis (non -pure comedo) in 21 (27.6%) patients, and DCIS without necrosis in 36 (47.4%) of cases, the latter group comprising largely classical cribri form or micropapillary architectural subtypes. Results: Flow cytometri c DNA analysis showed a significantly higher S-phase fraction in comed o DCIS than in the subgroup of DCIS tumors without necrosis (P < 0.01 (anova)). A preliminary analysis of disease recurrence and disease-fre e survival in a large series of 391 cases of pure DCIS showed that of 181 cases of pure comedo DCIS there were 19 local recurrences at the 7 -year stage (82% 7-year disease-free survival), with 5 local recurrenc es in 51 cases of DCIS with necrosis (non-pure comedo) (85% 7-year dis ease-free survival) and only 6 local recurrences in the 159 cases of t he DCIS-without-necrosis subgroup (94% 7-year disease-free survival). The x(2) value for the frequency of disease recurrence of all cases of DCIS with necrosis (i.e., combining the groups of comedo DCIS and DCI S with necrosis (non-pure comedo)) as compared to DCIS without histolo gical evidence of necrosis was 5705 (df = 2; P = 0.0001), and the x(2) for disease-free survival of types of DCIS with necrosis as compared to cases without necrosis was 178 (df = 2; P = 0.0001). This analysis indicates that the histological presence of necrosis appears to be a r elatively powerful predictor of increased disease recurrence and poore r disease-free survival after treatment for DCIS. Conclusions: Necrosi s in DCIS in the absentee of pure classical comedo morphology is a fea ture of more biologically aggressive in situ breast cancer with an int ermediate proliferative fraction as compared with the high proliferati ve fraction of pure comedo DCIS and the low proliferative fraction of DCIS without necrosis. There was no significant difference in DNA ploi dy (diploid or aneuploid) between the subgroups as assessed by x(2) an alysis. Further larger studies are required to establish if DCIS with necrosis (non-pure comedo) also shows a greater tendency to local recu rrence after breast conservation treatment than do subtypes of DCIS wi thout necrosis. DCIS with necrosis (non-pure comedo) should be adopted as a distinct histological subgroup of DCIS in future clinical studie s of in situ mammary carcinoma.