Assessment of necrosis and hypoxia in ductal carcinoma in situ of the breast: basis for a new classification

Modern classifications of ductal in situ carcinoma (DCIS) of the breast suf fer from unsatisfactory reproducibility in inter-observer circulation analy ses. Ducts in DCIS are markedly enlarged in the range of 360 mum in diamete r. Since the diffusion of oxygen from peri-ductal vessels is limited to 100 mum, cells in the center of DCIS are poorly oxygenated and become either n ecrotic or remain hypoxic but viable. There is evidence that such alternati ve fate is dictated by the biological characteristics of the neoplastic cel ls. Therefore, determination of presence or absence of necrosis in ducts up to 360 mum in diameter might represent a simple, reproducible, and biologi cally sound criterion to classify DCIS. In the present work, following this criterion, we classified 32 cases of intra-ductal lesions as either "necro tic" or "hypoxic" and tested the reproducibility of such classification usi ng K statistics. These cases had already been circulated among a group of E uropean pathologists, who classified the lesions using five different class ifications. The K statistics value obtained with the presently proposed sys tem was extremely high (0.91). It remains to be established whether the cla ssification "necrotic/hypoxic" withstands large inter-observer circulation analyses, whether it is predictive of the clinical evolution of DCIS, and w hether it might constitute a reproducible basis for selecting appropriate t reatments.