STEAP1 is overexpressed in prostate cancer and prostatic intraepithelial neoplasia lesions, and it is positively associated with Gleason score

Urol Oncol. 2014 Jan;32(1):53.e23-9. doi: 10.1016/j.urolonc.2013.08.028. Epub 2013 Nov 13.

Abstract

Background: Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a transmembrane protein of epithelial cells, mostly located at cell-cell junctions, and is overexpressed in several types of tumors, particularly prostate cancer. Several studies have pointed STEAP1 as a biomarker, but the clinical significance of its overexpression is not fully understood. Therefore, we aimed to establish the association of STEAP1 immunoreactivity with histologic diagnosis and clinical data of patients.

Materials and methods: Human tissue microarrays were constructed from tissue biopsies of prostate adenocarcinoma (n = 63), including nonneoplastic adjacent tissue (n = 41), prostatic intraepithelial neoplasia (PIN) lesions (n = 7), and 41 prostate samples from patients diagnosed with benign prostatic hyperplasia (BPH). The histologic features of tumor specimens were classified and clinical and pathologic data were retrieved. STEAP1 expression was evaluated by immunohistochemical analysis, and a semiquantitative quantification was performed using a grade score system based on the intensity and percentage of stained cells.

Results: Overexpression of STEAP1 protein was found in both plasma membrane and cytoplasm of prostate cancer and PIN lesions when compared with nonneoplastic adjacent tissue and BPH samples. Furthermore, its expression associates positively with higher Gleason scores, but not with other clinical data, such as age, prostate-specific antigen levels, pathologic stage, and metastasis. Regarding its role as a biomarker, STEAP1 is highly liable for distinguishing malignant prostate stages from BPH. On the contrary, it lacks specificity in distinguishing PIN lesions from prostate cancer.

Conclusions: STEAP1 is consistently overexpressed in malignant prostate tissue, namely adenocarcinoma and PIN lesions. Its overexpression in PIN lesions and positive association with higher Gleason scores suggest that STEAP1 could be involved in tumor initiation and progression. The high sensitivity and specificity for detection of malignant lesions suggests that STEAP1 may be of clinical usefulness in early disease diagnosis.

Keywords: BPH; Biomarker; Gleason score; PIN; Prostate cancer; STEAP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / biosynthesis*
  • Biomarkers, Tumor / biosynthesis
  • Disease Progression
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Oxidoreductases / biosynthesis*
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Intraepithelial Neoplasia / diagnosis
  • Prostatic Intraepithelial Neoplasia / metabolism*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / metabolism*
  • ROC Curve
  • Tissue Array Analysis

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Oxidoreductases
  • STEAP1 protein, human