RESUMO
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
Neoplasias da Próstata , Inibidor da Tripsina Pancreática de Kazal , Masculino , Humanos , Proteínas de Fusão Oncogênica/genética , Neoplasias da Próstata/patologia , Fatores de Transcrição/genética , Progressão da Doença , Regulador Transcricional ERG , Proteínas Nucleares , Proteínas Repressoras , Proteína Potenciadora do Homólogo 2 de ZesteRESUMO
Resumen El cáncer gástrico avanzado es una entidad que incluye dos situaciones clínicas distintas: el cáncer gástrico localmente avanzado no resecable y la enfermedad metastásica, cuyo tratamiento estándar es la quimioterapia. La sobreexpresión del receptor 2 del factor de crecimiento epidérmico humano (HER2) se puede presentar en esta enfermedad de un 9 % a un 38 % y ha sido el primer biomarcador predictivo utilizado para el tratamiento dirigido con trastuzumab en pacientes con tumores gástricos y de la región gastroesofágica avanzados. Se presenta en este artículo el caso de un paciente con cáncer gástrico avanzado con HER2 positivo manejado con quimioterapia convencional más trastuzumab como terapia blanco con adecuada respuesta clínica.
Abstract Advanced gastric cancer (AGC) is an entity that encompasses two distinct clinical situations: locally advanced unresectable gastric cancer and metastatic disease, with chemotherapy as the standard treatment. HER2 overexpression can occur in 9% to 38% of the cases with this disease and has been the first predictive biomarker used for trastuzumab-targeted therapy in patients with advanced gastric and gastroesophageal tumors. This article presents a patient with AGC and positive HER2 treated with conventional chemotherapy plus trastuzumab as targeted therapy with adequate clinical response.
