Clinicopathological Characteristics of a Distinct Tumor Phenotype: Invasive Lobular Carcinoma With Tubular Elements in the West German Study Group ADAPTcycle Trial

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Laboratory Investigation Pub Date : 2025-03-04 DOI:10.1016/j.labinv.2025.104125

Martin Radner , Sandy Burmeister , Katarzyna Jóźwiak , Nora Schaumann , Malte Gronewold , Mieke Raap , Stephan Bartels , Henriette Christgen , Leonie D. Kandt , Pia Hillmann , Ulrich Lehmann , Oleg Gluz , Monika Graeser , Sherko Kümmel , Christine zu Eulenburg , Nadia Harbeck , Hans Kreipe , Matthias Christgen

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Abstract

Invasive lobular carcinoma with tubular elements (ILC-TE) is a recently identified variant of invasive lobular breast carcinoma (ILC). The histology of ILC-TE is defined by noncohesive carcinoma cells mixed with cohesive tubular elements and complete loss of epithelial (E)-cadherin. Cell–cell adhesion is partially restored by switching from an E-cadherin–deficient to a placental (P)-cadherin–proficient status (EPS). The prevalence of ILC-TE remains unknown. Here, we report data from the central pathology review of >4500 hormone receptor–positive/HER2-negative breast cancer (BC) cases recruited to the West German Study Group (WSG) ADAPTcycle trial (NCT04055493). The central pathology review included prospective assessment of BC types, variants, and E-cadherin expression. Cases classified as ILC-TE were analyzed for their molecular features and clinicopathological characteristics. Pure ILC with complete loss of E-cadherin accounted for 630 of 4619 (13.6%) BC cases. ILC-TE accounted for 47 of 630 (7.5%) lobular carcinomas, making it more than twice as prevalent as mixed BC (NST/ILC). ILC-TE harbored deleterious CDH1/E-cadherin mutations in 27 of 35 (77%) cases tested. EPS was detected in 43 of 47 (91%) ILC-TE cases. EPS was significantly more common in ILC-TE than in classic ILC or other ILC variants (P < .001). Clinically, ILC-TE was associated with cT1 stage (P = .023), cN0 status (P = .024), lower histologic grade (P = .004), and lower Ki67 (P = .012). In contrast, solid ILC was associated with higher Ki67 (P = .006). Following preoperative endocrine therapy, higher post–preoperative endocrine therapy Ki67 levels were observed in trabecular ILC, solid-papillary ILC, and pleomorphic ILC (P < .001, P = .006, and P = .021, respectively). In summary, ILC-TE is a quite common ILC variant that is associated with EPS, less-aggressive clinical features, and slow growth.

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一种不同肿瘤表型的临床病理特征：浸润性小叶癌伴小管细胞（ILC-TE）

背景：浸润性小叶癌伴小管细胞（ILC- te）是最近发现的一种浸润性小叶乳腺癌（ILC）。ILC-TE的组织学定义为非内聚性癌细胞混合有内聚性管状细胞和e -钙粘蛋白的完全丧失。细胞-细胞粘附通过从e -钙粘蛋白缺乏状态切换到p -钙粘蛋白精通状态（EPS）部分恢复。ILC-TE的患病率尚不清楚。方法：在这里，我们报告了来自WSG ADAPTcycle试验（NCT04055493）招募的bbb4500例激素受体阳性/ her2阴性乳腺癌（BC）病例的中心病理回顾数据。中心病理回顾包括对BC类型、变异和E-cadherin表达的前瞻性评估。对分类为ILC-TE的病例进行分子特征和临床病理特征分析。结果：纯ILC伴E-cadherin完全缺失占630/4619例（13.6%）BC病例。ILC- te占47/630（7.5%）小叶癌，是混合型BC （NST/ILC）的两倍多。在27/35（77%）的检测病例中，ILC-TE携带有害的CDH1/E-cadherin突变。43/47（91%）的ILC-TE患者检出EPS。EPS在ILC- te中比在经典ILC或其他ILC变异体中更为常见(结论：ILC- te是一种相当常见的ILC变异体，与EPS相关，临床特征侵袭性较低，生长缓慢。

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来源期刊

Laboratory Investigation 医学-病理学

CiteScore

8.30

自引率

0.00%

发文量

125

审稿时长

2 months

期刊介绍： Laboratory Investigation is an international journal owned by the United States and Canadian Academy of Pathology. Laboratory Investigation offers prompt publication of high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease. Both human and experimental studies are welcome.