Clinicopathologic and genomic features of lobular like invasive mammary carcinoma: Is it a distinct entity? Journal Article
| Authors: | Yu, J.; da Silva, E. M.; La, H. S.; Clark, B. Z.; Fine, J. L.; Carter, G. J.; Villatoro, T. M.; Soong, T. R.; Lee, A. V.; Oesterreich, S.; Basili, T.; Blanco-Heredia, J.; Selenica, P.; Ye, Q.; Da Cruz Paula, A.; Dopeso, H.; Gazzo, A.; Marra, A.; Pareja, F.; Reis-Filho, J. S.; Bhargava, R. |
| Article Title: | Clinicopathologic and genomic features of lobular like invasive mammary carcinoma: Is it a distinct entity? |
| Abstract: | This study describes “lobular-like invasive mammary carcinomas” (LLIMCas), a group of low- to intermediate-grade invasive mammary carcinomas with discohesive, diffusely infiltrative cells showing retained circumferential membranous immunoreactivity for both E-cadherin and p120. We analyzed the clinical-pathologic features of 166 LLIMCas compared to 104 classical invasive lobular carcinomas (ILCs) and 100 grade 1 and 2 invasive ductal carcinomas (IDCs). Tumor size and pT stage of LLIMCas were intermediate between IDCs and ILCs, and yet often underestimated on imaging and showed frequent positive margins on the first resection. Despite histomorphologic similarities to classical ILC, the discohesion in LLIMCa was independent of E-cadherin/p120 immunophenotypic alteration. An exploratory, hypothesis-generating analysis of the genomic features of 14 randomly selected LLIMCas and classical ILCs (7 from each category) was performed utilizing an FDA-authorized targeted capture sequencing assay (MSK-IMPACT). None of the seven LLIMCas harbored CDH1 loss-of-function mutations, and none of the CDH1 alterations detected in two of the LLIMCas was pathogenic. In contrast, all seven ILCs harbored CDH1 loss-of-function mutations coupled with the loss of heterozygosity of the CDH1 wild-type allele. Four of the six evaluable LLIMCas were positive for CDH1 promoter methylation, which may partially explain the single-cell infiltrative morphology seen in LLIMCa. Further studies are warranted to better define the molecular basis of the discohesive cellular morphology in LLIMCa. Until more data becomes available, identifying LLIMCas and distinguishing them from typical IDCs and ILCs would be justified. In patients with LLIMCas, preoperative MRI should be entertained to guide surgical management. © 2023, The Author(s). |
| Keywords: | immunohistochemistry; adult; controlled study; human tissue; cancer surgery; major clinical study; overall survival; promoter region; missense mutation; cancer patient; cancer staging; outcome assessment; ki 67 antigen; tumor associated leukocyte; phenotype; tumor volume; randomized controlled trial; epidermal growth factor receptor 2; gene locus; gene frequency; immunoreactivity; retrospective study; dna methylation; in situ hybridization; heterozygosity; breast carcinoma; cancer size; heterozygosity loss; estrogen receptor; progesterone receptor; protein structure; cadherin; loss of function mutation; dna extraction; genomic dna; exploratory research; lobular carcinoma; invasive ductal carcinoma; machine learning; cancer prognosis; high throughput sequencing; human; male; female; article; segmentectomy; ductal breast carcinoma in situ; invasive lobular breast carcinoma |
| Journal Title: | npj Breast Cancer |
| Volume: | 9 |
| ISSN: | 2374-4677 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-07-13 |
| Start Page: | 60 |
| Language: | English |
| DOI: | 10.1038/s41523-023-00566-7 |
| PROVIDER: | scopus |
| PMCID: | PMC10345141 |
| PUBMED: | 37443169 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Jorge Reis-Filho -- Source: Scopus |
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639Reis-Filho -
145Da Cruz Paula -
216Pareja Zea -
95Da Silva -
189Selenica -
52Gazzo -
44Marra -
5Ye
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