Beerman H, Smit V T, Kluin P M, Bonsing B A, Hermans J, Cornelisse C J
Department of Pathology, Faculty of Medicine, University of Leiden, The Netherlands.
Cytometry. 1991;12(2):147-54. doi: 10.1002/cyto.990120208.
Flow cytometric DNA-ploidy analysis was used to investigate intratumor DNA stemline heterogeneity in primary breast carcinomas and lymph node metastases (LNM). The study was done in tumor specimens from 44 patients 35 of whom had LNM. In all, measurements were done in 214 different samples of primary tumors and 211 lymph nodes. Sixty-one percent (27/44) of the primary tumors were found to have multiple DNA aneuploid stemlines when the data of the separate samples per tumor (mean 4.9) were compared. Only five of 44 (11%) primary tumors were DNA diploid; two of these had DNA aneuploid metastases. Statistical analysis of these results indicated that, on average, four samples are needed for reliable determination of the DNA ploidy status of primary tumors by flow cytometry. In the majority of the cases (26/35), distinct tumor DNA stemlines found in LNM were also present in the primary tumor, which suggests that the generation of DNA ploidy diversity may have taken place prior to metastasis. Multiploidy was not related to tumor size but, particularly for LNM, was significantly correlated with age (r = 0.40, P = 0.02). The results of this study support the view that breast cancer is an extremely heterogeneous disease and that underestimation of this factor might account for the disagreement in literature about the prognostic value of DNA ploidy determinations.
采用流式细胞术DNA倍体分析来研究原发性乳腺癌及淋巴结转移癌（LNM）的肿瘤内DNA干系异质性。该研究在44例患者的肿瘤标本中进行，其中35例有淋巴结转移。总共对214个原发性肿瘤样本和211个淋巴结进行了测量。当比较每个肿瘤单独样本的数据（平均4.9个）时，发现61%（27/44）的原发性肿瘤有多个DNA非整倍体干系。44例原发性肿瘤中只有5例（11%）为DNA二倍体；其中2例有DNA非整倍体转移灶。对这些结果的统计分析表明，平均而言，通过流式细胞术可靠测定原发性肿瘤的DNA倍体状态需要4个样本。在大多数病例（26/35）中，在淋巴结转移灶中发现的不同肿瘤DNA干系也存在于原发性肿瘤中，这表明DNA倍体多样性的产生可能在转移之前就已发生。多倍体与肿瘤大小无关，但特别是对于淋巴结转移癌，与年龄显著相关（r = 0.40，P = 0.02）。本研究结果支持以下观点：乳腺癌是一种极其异质性的疾病，而对这一因素的低估可能是文献中关于DNA倍体测定预后价值存在分歧的原因。
