Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study).

Abstract

In the last years, many studies have highlighted the hypothesis that diabetes and hyperglycemia could be relevant for prostate cancer (PC) development and progression. We aimed to identify the prognostic value of tissue expression of androgen receptor (AR), Prostate-Specific Membrane Antigen (PSMA), Ki-67, insulin receptors (IR)  α and β, insulin growth factor-1 (IGF-1) receptor, in patients with PC and to evaluate their association with diabetes. We retrospectively collected data from 360 patients who underwent radical prostatectomy for PC or surgery for benign prostatic hyperplasia (BPH), between 2010 and 2020. We constructed tissue microarray for immunohistochemistry (IHC) analysis. In the final cohort (76 BPH and 284 PC), 57 (15.8%) patients had diabetes, 17 (22.37%) in BPH and 40 (14.08%) in PC (P = 0.08). IR-α was more expressed in patients with PC compared to the BPH Group (95.96% vs 4.04%; P <0.01). We found that AR was associated with increased risk of International Society of Urological Pathology (ISUP) score ≥4 (OR: 2.2; P <0.05), higher association with Ki-67 (OR: 2.2; P <0.05) and IR-α (OR: 5.7; P <0.05); IGF-1 receptor was associated with PSMA (OR: 2.8; P <0.05), Ki-67 (OR: 3.5; P <0.05) and IR-β (OR: 5.1; P <0.05). Finally, IGF-1 receptor was predictive of ISUP ≥ 4 (OR: 16.5; P =0.017) in patients with PC and diabetes. In the present study we highlighted how prostate cancer patients have a different protein expression in the tissue. This expression, and in particular that relating to IGF-1R, is associated with greater tumor aggressiveness in those patients with diabetes. We suppose that these results are attributable to an alteration of the insulin signal which therefore determines a greater mitogenic activity that can influence tumor progression.

• Authors: Giuseppe Broggi, Arturo Lo Giudice, Marina Di Mauro, Elisabetta Pricoco, Eliana Piombino, Matteo Ferro, Rosario Caltabiano, Giuseppe Morgia, Giorgio Ivan Russo
• Journal: Translational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 238 Pg. 25-35 (12 2021) ISSN: 1878-1810 [Electronic] United States
• PMID: 34314871 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• AR protein, human
• Antigens, CD
• Antigens, Surface
• Biomarkers, Tumor
• Insulin
• Receptors, Androgen
• INSR protein, human
• Receptor, IGF Type 1
• Receptor, Insulin
• FOLH1 protein, human
• Glutamate Carboxypeptidase II

Topics

• Aged
• Antigens, CD (metabolism)
• Antigens, Surface (metabolism)
• Biomarkers, Tumor (analysis, metabolism)
• Diabetes Mellitus (blood, metabolism)
• Glutamate Carboxypeptidase II (metabolism)
• Humans
• Immunohistochemistry
• Insulin (metabolism)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Prostatic Neoplasms (metabolism, mortality, pathology)
• Receptor, IGF Type 1 (metabolism)
• Receptor, Insulin (metabolism)
• Receptors, Androgen (metabolism)
• Retrospective Studies
• Tissue Array Analysis