Your browser doesn't support javascript.
loading
Determination of ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes to evaluate their association with clonal origin and disease progression in multifocal prostate cancer.
Segura-Moreno, Yenifer Yamile; Sanabria-Salas, María Carolina; Mesa-López De Mesa, Jorge Andrés; Varela-Ramirez, Rodolfo; Acosta-Vega, Natalia Lizeth; Serrano, Martha Lucía.
Afiliação
  • Segura-Moreno YY; Cancer Biology Research Group, Instituto Nacional de Cancerología, Bogotá, Colombia.
  • Sanabria-Salas MC; Department of Chemistry, Universidad Nacional de Colombia, Ciudad Universitaria, Bogotá, Colombia.
  • Mesa-López De Mesa JA; Cancer Biology Research Group, Instituto Nacional de Cancerología, Bogotá, Colombia.
  • Varela-Ramirez R; Department of Pathology, Instituto Nacional de Cancerología, Bogotá, Colombia.
  • Acosta-Vega NL; Department of Urology, Instituto Nacional de Cancerología, Bogotá, Colombia.
  • Serrano ML; Department of Urology, Universidad Nacional de Colombia, Bogotá, Colombia.
Cancer Rep (Hoboken) ; 6(2): e1728, 2023 02.
Article em En | MEDLINE | ID: mdl-36199157
BACKGROUND: The prognostic relevance of prostate cancer (PCa) molecular subtypes remains controversial, given the presence of multiple foci with the possibility of different subtypes in the same patient. AIM: To determine the clonal origin of heterogeneity in PCa and its association with disease progression, SPOP, ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes were analyzed. METHODS: A total of 103 samples from 20 PCa patients were analyzed; foci of adjacent non-tumor prostate tissue, HGPIN, GL3, GL4, GL5, and LN were examined to determine the presence of the TMPRSS2-ERG fusion and ERG, EZH2, NKX3.1, and SPINK-1 expression levels, using RT-PCR. Mutations in exons 6 and 7 of the SPOP gene were determined by sequencing. The presence of subtypes and molecular patterns were identified by combining all subtypes analyzed. To establish the clonal origin of multifocal PCa, molecular concordance between different foci of the same patient was determined. Association of these subtypes with histopathological groups and time to biochemical recurrence (BCR) was assessed. RESULTS: No mutation was found in SPOP in any sample. The ERG(+) subtype was the most frequent. The molecular pattern containing all four PCa subtypes was only detected in 3 samples (4%), all LN, but it was the most frequent (40%) in patients. Molecular discordance was the predominant status (55%) when all analyzed molecular characteristics were considered. It was possible to find all subtypes, starting as a preneoplastic lesion, and all but one LN molecular subtype were ERG(+) and NKX3.1 subtypes. Only the expression of the NKX3.1 gene was significantly different among the histopathological groups. No association was found between BCR time in patients and molecular subtypes or molecular concordance or between clinicopathological characteristics and molecular subtypes of ERG, EZH2, and SPINK-1. CONCLUSION: The predominance of molecular discordance in prostatic foci per patient, which reflects the multifocal origin of PCa foci, highlights the importance of analyzing multiple samples to establish the prognostic and therapeutic relevance of molecular subtypes in a patient. All the subtypes analyzed here are of early onset, starting from preneoplastic lesions. NKX3.1 gene expression is the only molecular characteristic that shows a progression pattern by sample.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Inibidor da Tripsina Pancreática de Kazal Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Inibidor da Tripsina Pancreática de Kazal Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article