Department of Biomedical and Neuromuscular Sciences, "M. Malpighi" Anatomic Pathology Section, University of Bologna, Italy.
Hum Pathol. 2013 Jul;44(7):1310-9. doi: 10.1016/j.humpath.2012.09.022. Epub 2013 Jan 18.
Nearly 80% of well-differentiated in situ duct carcinomas (g1 DCIS) have been shown to be multicentric (multilobar) lesions, while most in situ poorly differentiated duct carcinomas (g3 DCIS) were unifocal (unilobar) lesions. Here we present a clonality study of 15 cases of DCIS, all showing multiple foci. Twelve of these cases were associated with an invasive duct carcinoma. Fifteen cases of female breast cancer patients all showing multiple DCIS foci (5 g1 DCIS, 5 g2 DCIS, 5 g3 DCIS) were randomly selected and histologically studied using large histological sections. Care was taken to laser-microdissect DCIS foci that were most distantly located from one another in the same large section, and pertinent cells were genetically studied. Invasive duct carcinoma and ipsilateral lymph node metastases and/or contralateral lesions, whenever present, were additionally microdissected. DNA of neoplastic cells was purified, and the mtDNA D-loop region was sequenced. Genetic distance of different foci from the same case was visualized by phylogenetic analyses using the neighbor-joining method. Patients ranged in age from 36 to 87 years (mean 65.1). All 9 cases of widely spread DCIS were not clonal. Four of 6 cases that showed multiple adjacent foci were clonally related on mtDNA analysis. In the present series, 11/15 DCIS appeared as multiple synchronous primary breast tumors, genetically not related to one another. The present data enhance the view that breast can also show the field cancerization phenomenon, paralleling what has already been proposed in other organs.
已有研究表明，近 80%分化良好的原位导管癌（g1 DCIS）为多灶性（多叶性）病变，而大多数分化不良的原位导管癌（g3 DCIS）为单灶性（单叶性）病变。在此，我们报告了 15 例 DCIS 的克隆性研究，所有病例均显示多个病灶。其中 12 例与浸润性导管癌相关。随机选择了 15 例女性乳腺癌患者的 15 例均显示多个 DCIS 病灶（5 例 g1 DCIS、5 例 g2 DCIS、5 例 g3 DCIS），并使用大组织切片进行组织学研究。在同一大切片中，从彼此最远的位置仔细激光显微解剖 DCIS 病灶，并对相关细胞进行遗传研究。如有浸润性导管癌和同侧淋巴结转移和/或对侧病变，也会进行额外的显微解剖。纯化肿瘤细胞的 DNA，并对 mtDNA D-环区域进行测序。使用邻接法进行系统发育分析，以直观显示同一病例不同病灶之间的遗传距离。患者年龄为 36-87 岁（平均 65.1 岁）。所有 9 例广泛传播的 DCIS 均不是克隆性的。6 例显示多个相邻病灶的病例中有 4 例在 mtDNA 分析上存在克隆相关性。在本系列中，11/15 的 DCIS 表现为多个同步的原发性乳腺癌，彼此之间没有遗传关系。本研究结果进一步证实了乳腺癌也可能表现出“癌前病变”现象，与其他器官中已经提出的观点一致。
