Tissue immunostaining of candidate prognostic proteins in metastatic and non-metastatic prostate cancer

J Cancer Res Clin Oncol. 2023 Feb;149(2):567-577. doi: 10.1007/s00432-022-04274-w. Epub 2022 Aug 25.

Abstract

Purpose: Prostate cancer (PCa) lacks specific markers capable of distinguishing aggressive tumors from those with indolent behavior. Therefore, the aim of this study was to evaluate the immunostaining of candidate proteins (PTEN, AKT, TRPM8, and NKX3.1) through the immunohistochemistry technique (IHC) on patients with metastatic and non-metastatic PCa.

Methods: Tissues from 60 patients were divided into three groups categorized according to prognostic parameters: better prognosis (n = 20), worse prognosis (n = 23), and metastatic (n = 17). Immunostaining was analyzed by a pathologist and staining classifications were considered according to signal intensity: (0) no staining, (+) weak, and (++ and +++) intermediate to strong.

Results: AKT protein was associated (p = 0.012) and correlated (p = 0.014; Tau = - 0.288) with the prognostic groups. The immunostaining for TRPM8 (p = 0.010) and NKX3.1 (p = 0.003) proteins differed between malignant tumor and non-tumoral adjacent tissue as well as for proteins in cellular locations (nucleus and cytoplasm). TRPM8 was independently associated with the ISUP grade ≥ 4 (p = 0.024; OR = 8.373; 95% CI = 1.319-53.164). The NKX3.1 showed positive and predominantly strong immunostaining in all patients in both tumoral and non-tumoral adjacent tissues. All metastatic samples had positive immunostaining, with strong intensity for NKX3.1 (p = 0.021; Tau = - 0.302). In the non-metastatic group, this strong protein staining was not observed in any patients.

Conclusion: This study confirmed that NKX3.1 is highly specific for prostate tissue and indicated that NKX3.1, AKT, and TRPM8 may be candidate markers for prostate cancer prognosis.

Keywords: AKT; Immunohistochemistry; Metastasis; NKX3-1; PTEN; TRPM8.

MeSH terms

  • Homeodomain Proteins* / metabolism
  • Humans
  • Male
  • Prognosis
  • Prostatic Neoplasms* / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Transcription Factors / metabolism

Substances

  • Homeodomain Proteins
  • Proto-Oncogene Proteins c-akt
  • Transcription Factors