Calgranulin A (S100A8) Immunostaining: A Future Candidate for Risk Assessment in Patients with Non-Muscle-Invasive Bladder Cancer (NMIBC)

Adv Ther. 2018 Nov;35(11):2054-2068. doi: 10.1007/s12325-018-0789-7. Epub 2018 Sep 19.

Abstract

Introduction: There is an urgent need to identify patients with bladder cancer (BC) who are at high risk of recurrence or progression. Calgranulin A is a strong marker for muscle-invasive or advanced BC and recent studies have shown its potential for identifying patients at risk even in non-muscle-invasive bladder cancer (NMIBC). The present study examines risks of recurrence and progression dependent on immunostaining with calgranulin A in NMIBC.

Methods: Calgranulin A protein expression was evaluated through the immunohistochemistry of 158 randomly selected, transurethrally resected BC specimens of separate patients (pTa 89, pT1 69) using tissue microarrays. Kaplan-Meier survival analysis and Cox regression were performed to determine whether calgranulin A expression is associated with recurrence-free survival (RFS), progression-free survival (PFS), or cancer-specific survival (CSS).

Results: Calgranulin A expression is significantly different between pTa and pT1 tumors (p = 0.000, Mann-Whitney U test) and between tumor grades (p = 0.015, Kruskal-Wallis test). Kaplan-Meier estimates produced significant results for low and high calgranulin A expression concerning RFS [5y-RFS 70.4 ± 4.0% vs. 35.9 ± 12.5%, median RFS not reached (NR) vs. 12.0 ± 4.4 month, p = 0.029, log-rank test], PFS (5y-PFS 90.3 ± 2.7% vs. 51.5 ± 14.0%, median PFS NR in both groups, p = 0.000, log-rank test), and CSS (5y-CSS 92.9 ± 2.6% vs. 70.7 ± 12.4%, median CSS NR in both groups, p = 0.005, log-rank test). Calgranulin A remained an independent factor for RFS (p = 0.024, HR 2.43) and PFS (p = 0.002, HR 5.92) according to the multivariate Cox regression model.

Conclusions: Calgranulin A expression in NMIBC, detected through immunohistochemistry, is a promising marker for the identification of NMIBC patients at high risk of recurrence and progression.

Keywords: Bladder cancer; Calgranulin A; Cancer-specific survival; Immunohistochemistry; NMIBC; Oncology; Progression; Recurrence; S100A8; Tissue microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Calcium-Binding Proteins / analysis
  • Calcium-Binding Proteins / metabolism
  • Calgranulin A* / analysis
  • Calgranulin A* / metabolism
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Grading
  • Neoplasm Invasiveness / diagnosis*
  • Neoplasm Recurrence, Local / diagnosis*
  • Prognosis
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Assessment / methods*
  • Urinary Bladder Neoplasms* / diagnosis
  • Urinary Bladder Neoplasms* / metabolism
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Calgranulin A

Associated data

  • figshare/10.6084/m9.figshare.7047752