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Characterization of HOXB13 expression patterns in localized and metastatic castration-resistant prostate cancer.
Patel, Radhika A; Sayar, Erolcan; Coleman, Ilsa; Roudier, Martine P; Hanratty, Brian; Low, Jin-Yih; Jaiswal, Neha; Ajkunic, Azra; Dumpit, Ruth; Ercan, Caner; Salama, Nina; O'Brien, Valerie P; Isaacs, William B; Epstein, Jonathan I; De Marzo, Angelo M; Trock, Bruce J; Luo, Jun; Brennen, W Nathaniel; Tretiakova, Maria; Vakar-Lopez, Funda; True, Lawrence D; Goodrich, David W; Corey, Eva; Morrissey, Colm; Nelson, Peter S; Hurley, Paula J; Gulati, Roman; Haffner, Michael C.
Afiliação
  • Patel RA; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Sayar E; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Coleman I; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Roudier MP; Department of Urology, University of Washington, Seattle, WA, USA.
  • Hanratty B; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Low JY; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Jaiswal N; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Ajkunic A; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Dumpit R; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Ercan C; Institute of Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland.
  • Salama N; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • O'Brien VP; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Isaacs WB; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Epstein JI; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • De Marzo AM; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Trock BJ; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Luo J; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Brennen WN; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Tretiakova M; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Vakar-Lopez F; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • True LD; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Goodrich DW; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Corey E; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Morrissey C; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Nelson PS; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hurley PJ; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Gulati R; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • Haffner MC; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
J Pathol ; 262(1): 105-120, 2024 01.
Article em En | MEDLINE | ID: mdl-37850574
ABSTRACT
HOXB13 is a key lineage homeobox transcription factor that plays a critical role in the differentiation of the prostate gland. Several studies have suggested that HOXB13 alterations may be involved in prostate cancer development and progression. Despite its potential biological relevance, little is known about the expression of HOXB13 across the disease spectrum of prostate cancer. To this end, we validated a HOXB13 antibody using genetic controls and investigated HOXB13 protein expression in murine and human developing prostates, localized prostate cancers, and metastatic castration-resistant prostate cancers. We observed that HOXB13 expression increases during later stages of murine prostate development. All localized prostate cancers showed HOXB13 protein expression. Interestingly, lower HOXB13 expression levels were observed in higher-grade tumors, although no significant association between HOXB13 expression and recurrence or disease-specific survival was found. In advanced metastatic prostate cancers, HOXB13 expression was retained in the majority of tumors. While we observed lower levels of HOXB13 protein and mRNA levels in tumors with evidence of lineage plasticity, 84% of androgen receptor-negative castration-resistant prostate cancers and neuroendocrine prostate cancers (NEPCs) retained detectable levels of HOXB13. Notably, the reduced expression observed in NEPCs was associated with a gain of HOXB13 gene body CpG methylation. In comparison to the commonly used prostate lineage marker NKX3.1, HOXB13 showed greater sensitivity in detecting advanced metastatic prostate cancers. Additionally, in a cohort of 837 patients, 383 with prostatic and 454 with non-prostatic tumors, we found that HOXB13 immunohistochemistry had a 97% sensitivity and 99% specificity for prostatic origin. Taken together, our studies provide valuable insight into the expression pattern of HOXB13 during prostate development and cancer progression. Furthermore, our findings support the utility of HOXB13 as a diagnostic biomarker for prostate cancer, particularly to confirm the prostatic origin of advanced metastatic castration-resistant tumors. © 2023 The Pathological Society of Great Britain and Ireland.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias de Próstata Resistentes à Castração Limite: Animals / Humans / Male País/Região como assunto: Europa Idioma: En Revista: J Pathol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias de Próstata Resistentes à Castração Limite: Animals / Humans / Male País/Região como assunto: Europa Idioma: En Revista: J Pathol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos