The relationship between the ductal and lobular components of invasive ductolobular carcinomas (IDLC) has not been fully elucidated. In this study, the molecular alterations of both components were analyzed in a series of 20 IDLC that were selected, not only by morphologic criteria, but also by the loss of E-cadherin expression in the lobular component. We found that 80% of tumors shared alterations of driver genes in both components, being PIK3CA the most common alteration. In addition, 45% of IDLC carried CDH1 mutations in their lobular component that were absent in the ductal component. Fluorescent in situ hybridization analysis of the CDH1 gene excluded homozygous CDH1 loss as a frequent cause of E-cadherin loss in tumors without CDH1 mutations. In addition, no pathogenic mutations of catenin genes were detected in this series of tumors. In 25% of tumors, actionable mutations in PIK3CA, AKT1, and ERBB2 were found in only 1 component. Altogether, our results confirm that most IDLC derive from invasive carcinoma of no special type, in which a population of cells lose E-cadherin and acquire a lobular phenotype. The frequency of CDH1 mutations in IDLC appears to be lower than in conventional invasive lobular carcinomas, suggesting the implication of alternative mechanisms of E-cadherin loss. Moreover, molecular heterogeneity between ductal and lobular areas suggests the need for molecular characterization of both components to guide targeted therapies.

浸润性导管小叶癌（IDLC）的导管和小叶成分之间的关​​系尚未完全阐明。在这项研究中，不仅根据形态学标准，而且根据小叶成分中 E-钙粘蛋白表达的丧失，对一系列 20 个 IDLC 中两种成分的分子变化进行了分析。我们发现 80% 的肿瘤在两个组件中都有驱动基因的改变，其中PIK3CA是最常见的改变。此外，45% 的 IDLC 的小叶成分携带CDH1突变，而导管成分则不存在。 CDH1基因的荧光原位杂交分析排除了纯合子CDH1缺失是无CDH1突变的肿瘤中 E-钙粘蛋白缺失的常见原因。此外，在该系列肿瘤中未检测到连环蛋白基因的致病性突变。在 25% 的肿瘤中，仅在 1 个成分中发现了PIK3CA 、 AKT1和ERBB2的可操作突变。总而言之，我们的结果证实，大多数 IDLC 源自无特殊类型的浸润性癌，其中一群细胞失去 E-钙粘蛋白并获得小叶表型。 IDLC 中CDH1突变的频率似乎低于传统浸润性小叶癌，这表明 E-钙粘蛋白丢失的替代机制的含义。此外，导管和小叶区域之间的分子异质性表明需要对这两种成分进行分子表征以指导靶向治疗。