12/17/2023 0 Comments Nottingham histologic score 6 9When E-cadherin is absent or nonfunctional, p120 catenin undergoes redistribution from the cell membrane to the cytoplasm. Characteristically, ILC harbors biallelic inactivation of the CDH1 gene, often through a combination of pathogenic loss-of-function mutations coupled with loss-of-heterozygosity (LOH) of the CDH1 wild-type allele 7, 14. P120 catenin is a tyrosine kinase substrate anchored to the internal domain of E-cadherin in a juxtamembranous fashion 11, 12, 13. Immunohistochemical (IHC) assessment of E-cadherin with or without p120 and beta-catenin is often used to assist in the diagnosis of such cases.Į-cadherin is a transmembrane adhesion glycoprotein encoded by the CDH1 gene (16q22.1). Even though the diagnosis of IDC versus ILC is usually straightforward, cases with ambiguous histomorphology are not uncommon. More recently, attention has turned to the molecular and evolutionary differences between the two entities and their precursor lesions, laying the foundations for personalized management of breast cancers 6, 7, 8, 9, 10. The differences between IDC and ILC, from clinicopathological features to prognostic outcomes, have been extensively reported in the literature, sometimes with conflicting results 3, 4, 5. While IDCs typically show varying degrees of duct formation, ILCs are characterized by discohesive tumor cells with single-file infiltrative growth patterns dispersed in the fibrous stroma 2. Invasive mammary carcinoma of no special type, commonly referred to as invasive ductal carcinoma (IDC), and the special subtype of invasive lobular carcinoma (ILC) represent the two most common types of invasive breast carcinomas 1. In patients with LLIMCas, preoperative MRI should be entertained to guide surgical management. Until more data becomes available, identifying LLIMCas and distinguishing them from typical IDCs and ILCs would be justified. Further studies are warranted to better define the molecular basis of the discohesive cellular morphology in LLIMCa. Four of the six evaluable LLIMCas were positive for CDH1 promoter methylation, which may partially explain the single-cell infiltrative morphology seen in LLIMCa. In contrast, all seven ILCs harbored CDH1 loss-of-function mutations coupled with the loss of heterozygosity of the CDH1 wild-type allele. 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. 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). Despite histomorphologic similarities to classical ILC, the discohesion in LLIMCa was independent of E-cadherin/p120 immunophenotypic alteration. 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. 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). 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. Npj Breast Cancer volume 9, Article number: 60 ( 2023) Clinicopathologic and genomic features of lobular like invasive mammary carcinoma: is it a distinct entity?
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