NKX3.1 Expression in Non-Prostatic Tumors and Characterizing its Expression in Esophageal/Gastroesophageal Adenocarcinoma

Adv Anat Pathol. 2024 May 1;31(3):202-205. doi: 10.1097/PAP.0000000000000447. Epub 2024 Mar 25.


The NKX3.1 immunohistochemical stain is widely recognized as a highly sensitive and specific marker for prostate adenocarcinoma. Nevertheless, its expression has been documented in various nonprostatic tissues and malignancies. This review aims to provide an overview of NKX3.1 expression in diverse tumor types, with a specific focus on its aberrant expression in esophageal/gastroesophageal adenocarcinoma (E/GE-ADC). In our investigation, we explored the expression of NKX3.1 in a series of E/GE-ADC to shed light on its prevalence in this tumor category. A total of 50 samples, comprising primary and metastatic E/GE-ADC specimens from 34 patients, were subjected to immunohistochemical analysis. Stained sections were scored based on the intensity and distribution-categorized as negative, weak, moderate, or strong in either a focal or diffuse pattern. Strong staining corresponds to the intensity observed in normal prostate controls, while focal and diffuse staining denote <50% and ≥50% of tumor nuclei staining positive, respectively. Our semiquantitative scoring revealed that 6 (12%) of the primary and metastatic E/GE-ADC specimens exhibited variable positivity for NKX3.1. This finding suggests that E/GE-ADC can sporadically stain positive for NKX3.1, introducing potential challenges in definitively determining the primary site of origin in certain clinical scenarios. Along with a literature review of NKX3.1 expression in other tumor types, our study provides additional important information about the extent to which this immunostain can be seen in E/GE-ADCs, which, to our knowledge, has not been reported.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma* / pathology
  • Biomarkers, Tumor / analysis
  • Esophageal Neoplasms*
  • Homeodomain Proteins / analysis
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Prostate / pathology
  • Prostatic Neoplasms* / pathology
  • Transcription Factors / metabolism


  • Biomarkers, Tumor
  • Homeodomain Proteins
  • Transcription Factors
  • NKX3-1 protein, human

Supplementary concepts

  • Adenocarcinoma Of Esophagus