乳腺小叶原位癌、导管原位癌及相关浸润性癌的遗传关系。
Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and associated invasive carcinoma of the breast.
作者信息
Buerger H, Simon R, Schäfer K L, Diallo R, Littmann R, Poremba C, van Diest P J, Dockhorn-Dworniczak B, Böcker W
机构信息
Gerhard-Domagk-Institute of Pathology, University of Münster, Germany.
出版信息
Mol Pathol. 2000 Jun;53(3):118-21. doi: 10.1136/mp.53.3.118.
AIMS
The mutual relation of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) of the breast, as accepted precursor lesions of invasive breast cancer, is controversial. Because they display genetic heterogeneity, it is not clear how genetically advanced these entities are and what causes the transition to an invasive carcinoma.
METHODS
Six cases of LCIS, four of them with associated lobular invasive carcinoma, four cases of intermediately differentiated DCIS with an associated invasive lobular carcinoma, and nine cases of intermediately and poorly differentiated DCIS with associated ductal invasive carcinoma were investigated by means of comparative genomic hybridisation (CGH) after microdissection and immunohistochemical staining of E-cadherin.
RESULTS
LCIS was characterised by a low average rate of copy number changes, no evidence of amplifications, and a high rate of gains and losses of chromosomal material at 1q and 16q, respectively. A high degree of genetic homology with well differentiated DCIS was obvious, as reported previously. The cases of intermediately differentiated DCIS with associated lobular invasive components and lobular differentiation revealed striking homologies, and a significant difference of E-cadherin expression. The comparison of preinvasive and invasive breast lesions, irrespective of differentiation within the same patient, revealed no specific alteration that might be associated with invasion. Genetic alterations seen in invasive carcinoma were not necessarily seen in the adjacent precursor lesions.
CONCLUSIONS
These results provide strong evidence that invasive breast cancer is a disease with multiple cytogenetic subclones already present in preinvasive lesions. Moreover, specific CGH alterations associated with invasion were not observed. Furthermore, the close genetic association between well differentiated and a subgroup of intermediately differentiated DCIS and LCIS led to the hypothesis that LCIS and a subgroup of DCIS are different phenotypic forms of a common genotype.
目的
乳腺小叶原位癌（LCIS）和导管原位癌（DCIS）作为浸润性乳腺癌公认的前驱病变，它们之间的相互关系存在争议。由于它们表现出基因异质性，目前尚不清楚这些实体在基因上的进展程度以及是什么导致向浸润性癌的转变。
方法
对6例LCIS（其中4例伴有小叶浸润癌）、4例伴有小叶浸润癌的中度分化DCIS以及9例伴有导管浸润癌的中度和低分化DCIS进行了研究，采用显微切割后的比较基因组杂交（CGH）以及E-钙黏蛋白的免疫组织化学染色。
结果
LCIS的特征是平均拷贝数变化率低，无扩增证据，且在1q和16q分别有较高的染色体物质增加和丢失率。如先前报道，与高分化DCIS有高度的基因同源性。伴有小叶浸润成分和小叶分化的中度分化DCIS病例显示出显著的同源性，以及E-钙黏蛋白表达的显著差异。对同一患者内的浸润前和浸润性乳腺病变进行比较，无论其分化程度如何，均未发现可能与浸润相关的特异性改变。浸润性癌中所见的基因改变不一定见于相邻的前驱病变。
结论
这些结果提供了有力证据，表明浸润性乳腺癌是一种在浸润前病变中就已存在多个细胞遗传学亚克隆的疾病。此外，未观察到与浸润相关的特异性CGH改变。此外，高分化和一部分中度分化DCIS与LCIS之间密切的基因关联导致了这样一种假说，即LCIS和一部分DCIS是共同基因型的不同表型形式。
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