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RB1 Genetic Alterations in Estrogen Receptor-Positive Breast Carcinomas: Correlation With Neuroendocrine Differentiation.
Schwartz, Christopher J; Marra, Antonio; Selenica, Pier; Gazzo, Andrea; Tan, Kiki; Ross, Dara; Razavi, Pedram; Chandarlapaty, Sarat; Weigelt, Britta; Reis-Filho, Jorge S; Brogi, Edi; Pareja, Fresia; Wen, Hannah Y.
Afiliação
  • Schwartz CJ; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: schwarc1@mskcc.org.
  • Marra A; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Selenica P; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Gazzo A; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Tan K; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Ross D; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Razavi P; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Chandarlapaty S; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Weigelt B; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Reis-Filho JS; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Now with AstraZeneca, Gaithersburg, Maryland.
  • Brogi E; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Pareja F; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Wen HY; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Mod Pathol ; 37(8): 100541, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38897452
ABSTRACT
Genetic alterations in the retinoblastoma susceptibility gene (RB1) are present in up to 40% of triple-negative breast cancers (BCs) and frequent in tumors with neuroendocrine differentiation, including small cell neuroendocrine carcinoma. Data on RB1 genetic alterations in estrogen receptor (ER)-positive BCs are scarce. In this study, we sought to define the morphologic, immunohistochemical, and genetic features of ER-positive BCs harboring somatic alterations in RB1, with emphasis on neuroendocrine differentiation. ER-positive BCs with pathogenic RB1 genetic alterations were identified in <1% of cases (N = 55) from a cohort of 6026 BCs previously subjected to targeted next-generation sequencing, including 23 primary BCs (pBCs) and 32 recurrent/metastatic BCs (mBCs). In cases where loss of heterozygosity of the wild-type RB1 allele could be assessed (93%, 51/55), most pBCs (82%, 18/22) and mBCs (90%, 26/29) exhibited biallelic RB1 inactivation, primarily through loss-of-function mutation and loss of heterozygosity (98%, 43/44). Upon histologic review, a subset of RB1-altered tumors exhibited neuroendocrine morphology (13%, 7/55), which correlated with expression of neuroendocrine markers (39%, 9/23) in both pBCs (27%, 3/11) and mBCs (50%, 6/12). Loss of Rb protein expression was observed in BCs with biallelic RB1 loss only, with similar frequency in pBCs (82%, 9/11) and mBCs (75%, 9/12). All cases with neuroendocrine marker expression (n = 9) and/or neuroendocrine morphology (n = 7) harbored biallelic genetic inactivation of RB1 and exhibited Rb loss of expression. TP53 (53%, 29/55) and PIK3CA (45%, 25/55) were the most frequently comutated genes across the cohort. Overall, these findings suggest that ER-positive BCs with biallelic RB1 genetic alterations frequently exhibit Rb protein loss, which correlates with neuroendocrine differentiation in select BCs. This study provides insights into the molecular and phenotypic heterogeneity of BCs with RB1 genetic inactivation, underscoring the need for further research into the potential clinical implications associated with these tumors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Receptores de Estrogênio / Carcinoma Neuroendócrino / Ubiquitina-Proteína Ligases / Proteínas de Ligação a Retinoblastoma Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Mod Pathol Assunto da revista: PATOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Receptores de Estrogênio / Carcinoma Neuroendócrino / Ubiquitina-Proteína Ligases / Proteínas de Ligação a Retinoblastoma Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Mod Pathol Assunto da revista: PATOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos