Henry Ford Hospital, Detroit, MI, Pathology.
Curr Genomics. 2006;7(8):523-32. doi: 10.2174/138920206779315719.
Pleomorphic variant of invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular carcinoma (ILC). Its in situ counterpart, pleomorphic lobular carcinoma in situ (PLCIS) is a recently described entity. Morphologically it has the typical architectural pattern of LCIS, but the neoplastic cells resemble intermediate grade DCIS. Molecular signatures that distinguish PLCIS from DCIS and LCIS would provide additional tools to aid in the histopathologic classification of PLCIS as a lesion distinct from LCIS and DCIS. CIS lesions, obtained from a study cohort of 38 breast cancer patients, were divided into 18 DCIS, 14 PLCIS and 6 LCIS. DNA from microdissected archival tissue was interrogated for loss or gain of 112 breast-cancer-specific genes using the Multiplex Ligation-dependent Probe Amplification Assay (MLPA). Classification Regression Tree (CART) analysis was employed to develop a gene-based molecular classification to distinguish or separate out PLCIS from DCIS and LCIS. Molecular classification via CART, based on gene copy number, agreed with histopathology in 34/38 CIS cases. Loss of CASP1 was predictive of LCIS (n=4) with one misclassified PLCIS. Gain of RELA predicted only the LCIS classification (n=2 cases). STK15 and TNFRSF1B were predictive only for DCIS with no misclassifications. Gain of EHF and TNFRSF1B and loss of NCOA3 were predictive of PLCIS, but not without misclassification. Molecular reclassification by CART was accomplished in 4 CIS cases: 1 PLCIS was reclassified as LCIS, 1 LCIS reclassified as PLCIS, and 2 DCIS cases as PLCIS. This study provides additional rationale for molecular modeling strategies in the evaluation of CIS lesions. This diagnostic aid may serve to minimize misclassification between PLCIS and DCIS, and PLCIS and LCIS, aiding to increase accuracy in the differential diagnosis of CIS lesions.
多形性浸润性小叶癌（PILC）是浸润性小叶癌（ILC）的一种侵袭性变体。其原位对应物，多形性小叶原位癌（PLCIS）是最近描述的实体。从形态上看，它具有 LCIS 的典型结构模式，但肿瘤细胞类似于中等级别的 DCIS。将 PLCIS 与 DCIS 和 LCIS 区分开来的分子特征将为帮助病理组织学分类提供额外的工具，将 PLCIS 作为一种与 LCIS 和 DCIS 不同的病变进行分类。从 38 名乳腺癌患者的研究队列中获得的 CIS 病变分为 18 例 DCIS、14 例 PLCIS 和 6 例 LCIS。使用多重连接依赖性探针扩增检测（MLPA）对微切割存档组织中的 DNA 进行了 112 个乳腺癌特异性基因的缺失或获得检测。采用分类回归树（CART）分析来开发基于基因的分子分类，以区分或区分 PLCIS 与 DCIS 和 LCIS。基于基因拷贝数的 CART 分子分类与 38 例 CIS 病例中的组织病理学一致。CASP1 的缺失预测了 LCIS（n=4），其中有 1 例误诊为 PLCIS。RELA 的获得仅预测了 LCIS 分类（n=2 例）。STK15 和 TNFRSF1B 仅预测 DCIS，没有误诊。EHF 和 TNFRSF1B 的获得以及 NCOA3 的缺失预测了 PLCIS，但也有误诊。CART 对 4 例 CIS 进行了重新分类：1 例 PLCIS 重新分类为 LCIS，1 例 LCIS 重新分类为 PLCIS，2 例 DCIS 病例重新分类为 PLCIS。本研究为 CIS 病变的分子建模策略提供了更多的依据。这种诊断辅助手段可能有助于减少 PLCIS 与 DCIS 之间以及 PLCIS 与 LCIS 之间的误诊，从而提高 CIS 病变的鉴别诊断准确性。
