Mandard A M, Denoux Y, Herlin P, Duigou F, van De Vijver M J, Clahsen P C, van Den Broek L, Sahmoud T M, Henry-Amar M, van De Velde C J
Department of Pathology, Centre François Baclesse, Caen, France.
Cancer. 2000 Oct 15;89(8):1748-57. doi: 10.1002/1097-0142(20001015)89:8<1748::aid-cncr15>3.0.co;2-e.
The clinical relevance of DNA image cytometry (ICM) and flow cytometry (FCM) remains under investigation in breast carcinoma. The objective of the current work was to study the prognostic value of DNA ICM and FCM in a series of patients randomized in a control trial. A multivariate analysis has been performed including other factors still under investigation such as Ki-67 index, mitotic count, microvessel density, and P53 and Bcl-2 expression.
Two hundred and eighty-one patients were randomized in the European Organization for Research and Treatment of Cancer 10854 trial comparing surgery followed by one course of perioperative chemotherapy versus surgery alone. Tumor parameters studied were pT, multicentricity, tumor grading according to modified Scarff-Bloom-Richardson, estrogen receptors, mitotic count per 1.7 mm(2), MIB-1, and BCL-2 scores, microvessel density, and p53 expression. ICM DNA parameters studied from paraffin embedded specimens, were DNA ploidy, proliferative index, 2c deviation index, malignancy grade, and Auer-Baldetorp typing. FCM DNA parameters analyzed on the same samples were ploidy and S-phase fraction statistics. The influence of tumor parameters, and DNA parameters on overall survival (OS), disease free survival (DFS), and metastasis-free survival (MFS) was evaluated using the Cox model. Median follow-up was 82 months.
For OS, the prognostic parameters retained were pathologic tumor size (pT) and mitotic index (MI). Overall survival was 94% and 68% for tumors pT1/MI less than 10 and pT2-3 MI greater than or equal to 10, respectively. For DFS, age, multicentricity, and grading according to modified Scarff and Bloom were predicting factors with the same relative risk. Disease free survival was 96%, 78% and 68% respectively, when 1, 2, or 3 of those factors were present. For MFS, the only retained predicting factor was MI. MFS was 97% and 73% when MI was less than 10 and MI was greater than or equal to 10, respectively.
Evaluation of proliferative compartment was the most important predicting factor for OS and MFS in the current series of premenopausal lymph node negative patients with breast invasive carcinoma. When working on paraffin embedded tissue, the best way of assessing it was MI count. ICM DNA analysis results were not selected in multivariate analysis. DNA analysis by FCM should be considered as an unsuitable technique when working on paraffin embedded tissue.
在乳腺癌中，DNA图像细胞术（ICM）和流式细胞术（FCM）的临床相关性仍在研究中。当前研究的目的是在一项对照试验中随机分组的一系列患者中研究DNA ICM和FCM的预后价值。已进行多变量分析，纳入了其他仍在研究的因素，如Ki-67指数、有丝分裂计数、微血管密度以及P53和Bcl-2表达。
281例患者被随机纳入欧洲癌症研究与治疗组织10854试验，该试验比较了手术加一个疗程围手术期化疗与单纯手术。研究的肿瘤参数包括pT、多中心性、根据改良的斯卡夫-布鲁姆-理查森法进行的肿瘤分级、雌激素受体、每1.7平方毫米的有丝分裂计数、MIB-1和BCL-2评分、微血管密度以及p53表达。从石蜡包埋标本中研究的ICM DNA参数包括DNA倍体、增殖指数、2c偏差指数、恶性程度分级以及奥尔-巴尔德托普分型。在相同样本上分析的FCM DNA参数是倍体和S期分数统计。使用Cox模型评估肿瘤参数和DNA参数对总生存期（OS）、无病生存期（DFS）和无转移生存期（MFS）的影响。中位随访时间为82个月。
对于OS，保留的预后参数是病理肿瘤大小（pT）和有丝分裂指数（MI）。pT1/MI小于10和pT2 - 3 MI大于或等于10的肿瘤的总生存期分别为94%和68%。对于DFS，年龄、多中心性以及根据改良的斯卡夫和布鲁姆法进行的分级是具有相同相对风险的预测因素。当存在这些因素中的1个、2个或3个时，无病生存期分别为96%、78%和68%。对于MFS，唯一保留下来的预测因素是MI。MI小于10和MI大于或等于10时，MFS分别为97%和73%。
在当前这组绝经前淋巴结阴性的乳腺浸润癌患者中，对增殖区的评估是OS和MFS最重要的预测因素。在处理石蜡包埋组织时，评估它的最佳方法是有丝分裂计数。ICM DNA分析结果在多变量分析中未被选中。在处理石蜡包埋组织时，FCM DNA分析应被视为一种不合适的技术。
