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Germline BRCA-Associated Endometrial Carcinoma Is a Distinct Clinicopathologic Entity.
de Jonge, Marthe M; Ritterhouse, Lauren L; de Kroon, Cornelis D; Vreeswijk, Maaike P G; Segal, Jeremy P; Puranik, Rutika; Hollema, Harry; Rookus, Matti A; van Asperen, Christi J; van Leeuwen, Flora E; Smit, Vincent T H B M; Howitt, Brooke E; Bosse, Tjalling.
Afiliação
  • de Jonge MM; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
  • Ritterhouse LL; Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago, Chicago, Illinois.
  • de Kroon CD; Department of Gynaecology, Leiden University Medical Center, Leiden, the Netherlands.
  • Vreeswijk MPG; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • Segal JP; Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago, Chicago, Illinois.
  • Hollema H; Department of Pathology, University Medical Center Groningen, Groningen, the Netherlands.
  • Rookus MA; Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • van Asperen CJ; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • van Leeuwen FE; Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Smit VTHBM; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
  • Howitt BE; Department of Pathology, Stanford University School of Medicine, Stanford, California.
  • Bosse T; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands. T.Bosse@lumc.nl.
Clin Cancer Res ; 25(24): 7517-7526, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31492746
ABSTRACT

PURPOSE:

Whether endometrial carcinoma (EC) should be considered part of the gBRCA1/2-associated hereditary breast and ovarian cancer (HBOC) syndrome is topic of debate. We sought to assess whether ECs occurring in gBRCA carriers are enriched for clinicopathologic and molecular characteristics, thereby supporting a causal relationship. EXPERIMENTAL

DESIGN:

Thirty-eight gBRCA carriers that developed EC were selected from the nationwide cohort study on hereditary breast and ovarian cancer in the Netherlands (HEBON), and these were supplemented with four institutional cases. Tumor tissue was retrieved via PALGA (Dutch Pathology Registry). Nineteen morphologic features were scored and histotype was determined by three expert gynecologic pathologists, blinded for molecular analyses (UCM-OncoPlus Assay including 1213 genes). ECs with LOH of the gBRCA-wild-type allele (gBRCA/LOHpos) were defined "gBRCA-associated," those without LOH (gBRCA/LOHneg) were defined "sporadic."

RESULTS:

LOH could be assessed for 40 ECs (30 gBRCA1, 10 gBRCA2), of which 60% were gBRCA/LOHpos. gBRCA/LOHpos ECs were more frequently of nonendometrioid (58%, P = 0.001) and grade 3 histology (79%, P < 0.001). All but two were in the TP53-mutated TCGA-subgroup (91.7%, P < 0.001). In contrast, gBRCA/LOHneg ECs were mainly grade 1 endometrioid EC (94%) and showed a more heterogeneous distribution of TCGA-molecular subgroups POLE-mutated (6.3%), MSI-high (25%), NSMP (62.5%), and TP53-mutated (6.3%).

CONCLUSIONS:

We provide novel evidence in favor of EC being part of the gBRCA-associated HBOC-syndrome. gBRCA-associated ECs are enriched for EC subtypes associated with unfavorable clinical outcome. These findings have profound therapeutic consequences as these patients may benefit from treatment strategies such as PARP inhibitors. In addition, it should influence counseling and surveillance of gBRCA carriers.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Neoplasias do Endométrio / Mutação em Linhagem Germinativa / Proteína BRCA1 / Perda de Heterozigosidade / Proteína BRCA2 Limite: Adulto / Idoso / Feminino / Humanos / Meia-Idade Idioma: Inglês Revista: Clin Cancer Res Assunto da revista: Neoplasias Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Holanda

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Neoplasias do Endométrio / Mutação em Linhagem Germinativa / Proteína BRCA1 / Perda de Heterozigosidade / Proteína BRCA2 Limite: Adulto / Idoso / Feminino / Humanos / Meia-Idade Idioma: Inglês Revista: Clin Cancer Res Assunto da revista: Neoplasias Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Holanda
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