Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions.
Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions.
复制标题
DOI：
10.1186/bcr3222
复制
发表时间：
2012-07-09
期刊：
影响因子：
--
通讯作者：
King TA
中科院分区：
文献类型：
--
作者：
Andrade VP;Ostrovnaya I;Seshan VE;Morrogh M;Giri D;Olvera N;De Brot M;Morrow M;Begg CB;King TA
小叶原位癌（LCIS）已被接受为浸润性乳腺癌发展的风险标志物，但现代乳腺癌发生模型包括LCIS作为低级别癌的前体。我们提供的证据支持LCIS的克隆起源和乳腺导管和小叶表型的同步雌激素受体阳性恶性病变。从2003年到2008年，术前确定了接受乳房切除术的既往LCIS患者。标本广泛取样，冷冻块进行筛选LCIS和共存的恶性病变，并进行显微解剖。将来自65名患者的样品与Affyssin SNP 6.0阵列平台杂交。评估具有LCIS样本和相关导管原位癌（DCIS）或侵袭性肿瘤样本的病例的体细胞拷贝数变化模式，以评估克隆相关性的证据。在44例病例中确定了LCIS，其中21例病例还确定了DCIS和/或浸润性病变。共有17对肿瘤具有足够的DNA/阵列数据用于分析，包括9对LCIS/浸润性小叶癌、4对LCIS/DCIS和4对LCIS/浸润性导管癌。总体而言，7对（41%）被判定为克隆相关;在5个（29%）证据表明克隆性，但模棱两可，5个（29%）被认为是独立的。在所有匹配的病变类型和低和高组织学分级中观察到克隆对。我们还显示了LCIS、DCIS和浸润性导管癌患者匹配三联体之间克隆性的轶事证据。我们的研究结果支持LCIS作为高级别和低级别导管癌和小叶癌发展的前体的作用。
Lobular carcinoma in situ (LCIS) has been accepted as a marker of risk for the development of invasive breast cancer, yet modern models of breast carcinogenesis include LCIS as a precursor of low-grade carcinomas. We provide evidence favoring a clonal origin for LCIS and synchronous estrogen receptor-positive malignant lesions of the ductal and lobular phenotype. Patients with prior LCIS undergoing mastectomy were identified preoperatively from 2003 to 2008. Specimens were widely sampled, and frozen blocks were screened for LCIS and co-existing malignant lesions, and were subject to microdissection. Samples from 65 patients were hybridized to the Affymetrix SNP 6.0 array platform. Cases with both an LCIS sample and an associated ductal carcinoma in situ (DCIS) or invasive tumor sample were evaluated for patterns of somatic copy number changes to assess evidence of clonal relatedness. LCIS was identified in 44 of the cases, and among these a DCIS and/or invasive lesion was also identified in 21 cases. A total of 17 tumor pairs had adequate DNA/array data for analysis, including nine pairs of LCIS/invasive lobular cancer, four pairs of LCIS/DCIS, and four pairs of LCIS/invasive ductal cancer. Overall, seven pairs (41%) were judged to be clonally related; in five (29%) evidence suggested clonality but was equivocal, and five (29%) were considered independent. Clonal pairs were observed with all matched lesion types and low and high histological grades. We also show anecdotal evidence of clonality between a patient-matched triplet of LCIS, DCIS, and invasive ductal cancer. Our results support the role of LCIS as a precursor in the development of both high-grade and low-grade ductal and lobular cancers.
登录
查看更多内容
影响因子：
6.2
作者：
Hwang, ES;Nyante, SJ;Waldman, FM
通讯作者：
Waldman, FM
影响因子：
5.6
作者：
Jacobs, TW;Pliss, N;Schnitt, SJ
通讯作者：
Schnitt, SJ
影响因子：
11.5
作者：
Allred, D. Craig;Wu, Yun;Medina, Dan
通讯作者：
Medina, Dan
影响因子：
4.5
作者：
Moriya, Takuya;Kozuka, Yuji;Tan, Puay-Hoon
通讯作者：
Tan, Puay-Hoon
影响因子：
3.7
作者：
King, Tari A.;Sakr, Rita A.;Morrow, Monica
通讯作者：
Morrow, Monica