Poller D N, Silverstein M J, Galea M, Locker A P, Elston C W, Blamey R W, Ellis I O
Department of Histopathology, City Hospital, Nottingham, England.
Mod Pathol. 1994 Feb;7(2):257-62.
The diagnosis of ductal carcinoma in situ of the breast (DCIS) has become common with the advent of breast screening programs.
Proliferation indices (S-phase fraction) were studied in 76 cases of pure DCIS. Tumors were classified according to conventional criteria and also according to a novel simplified classification based on cellular necrosis 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 cribriform or micropapillary architectural subtypes.
Flow cytometric DNA analysis showed a significantly higher S-phase fraction in comedo DCIS than in the subgroup of DCIS tumors without necrosis (P < 0.01 [anova]). A preliminary analysis of disease recurrence and disease-free 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 recurrences in 51 cases of DCIS with necrosis (non-pure comedo) (85% 7-year disease-free survival) and only 6 local recurrences in the 159 cases of the DCIS-without-necrosis subgroup (94% 7-year disease-free survival). The chi 2 value for the frequency of disease recurrence of all cases of DCIS with necrosis (i.e., combining the groups of comedo DCIS and DCIS with necrosis (non-pure comedo)) as compared to DCIS without histological evidence of necrosis was 5705 (df = 2; P = 0.0001), and the chi 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 relatively powerful predictor of increased disease recurrence and poorer disease-free survival after treatment for DCIS.
Necrosis in DCIS in the absence of pure classical comedo morphology is a feature of more biologically aggressive in situ breast cancer with an intermediate proliferative fraction as compared with the high proliferative fraction of pure comedo DCIS and the low proliferative fraction of DCIS without necrosis. There was no significant difference in DNA ploidy (diploid or aneuploid) between the subgroups as assessed by chi 2 analysis. Further larger studies are required to establish if DCIS with necrosis (non-pure comedo) also shows a greater tendency to local recurrence after breast conservation treatment than do subtypes of DCIS without necrosis. DCIS with necrosis (non-pure comedo) should be adopted as a distinct histological subgroup of DCIS in future clinical studies of in situ mammary carcinoma.
随着乳腺筛查项目的出现，乳腺导管原位癌（DCIS）的诊断已变得常见。
对76例纯DCIS病例进行增殖指数（S期分数）研究。肿瘤根据传统标准分类，也根据基于细胞坏死和形态学的新型简化分类进行分类。这种新分类定义了三个不同的肿瘤组：19例（25.0%）为纯粉刺型，21例（27.6%）为伴有坏死的DCIS（非纯粉刺型），36例（47.4%）为无坏死的DCIS，后一组主要包括经典筛状或微乳头结构亚型。
流式细胞术DNA分析显示，粉刺型DCIS的S期分数显著高于无坏死的DCIS肿瘤亚组（P < 0.01[方差分析]）。对391例纯DCIS病例的疾病复发和无病生存的初步分析表明，在181例纯粉刺型DCIS中，7年时有19例局部复发（7年无病生存率82%），在51例伴有坏死的DCIS（非纯粉刺型）中有5例局部复发（7年无病生存率85%），而在159例无坏死的DCIS亚组中仅有6例局部复发（7年无病生存率94%）。与无组织学坏死证据的DCIS相比，所有伴有坏死的DCIS病例（即粉刺型DCIS组和伴有坏死的DCIS（非纯粉刺型）组合）的疾病复发频率的卡方值为57.05（自由度 = 2；P = 0.0001），伴有坏死的DCIS类型与无坏死病例的无病生存的卡方值为17.8（自由度 = 2；P = 0.0001）。该分析表明，坏死的组织学存在似乎是DCIS治疗后疾病复发增加和无病生存较差的一个相对有力的预测指标。
在不存在纯经典粉刺形态的情况下，DCIS中的坏死是一种生物学上更具侵袭性的原位乳腺癌的特征，其增殖分数处于中间水平，与纯粉刺型DCIS的高增殖分数和无坏死的DCIS的低增殖分数相比。通过卡方分析评估，各亚组之间的DNA倍体（二倍体或非整倍体）无显著差异。需要进一步更大规模的研究来确定伴有坏死的DCIS（非纯粉刺型）在保乳治疗后是否也比无坏死的DCIS亚型有更大的局部复发倾向。伴有坏死的DCIS（非纯粉刺型）应在未来原位乳腺癌的临床研究中作为DCIS的一个独特组织学亚组采用。
