Relationship between concentration of heavy metals in bladder cancer tissue and molecular types using luminal GATA3 and basal cytokeratin 5/6 markers.

INTRODUCTION AND OBJECTIVES: Data on molecular sub-typing of bladder cancer (BC) associated with heavy metals (HMTE) are lacking. Clinical significance of luminal (GATA3) and basal (cytokeratin 5/6) markers in BC is controversial. Therefore, objective is to use these markers to characterize BC associated with HMTE into luminal and basal, and to investigate their clinical significance. METHODS: Study included 143 patients undergoing radical cystectomy (RC) for urothelial carcinoma. Two fresh samples were obtained from cancerous and non-cancerous RC specimens to measure [aluminum-Al, cadmium-Cd, cobalt-Co, chromium-Cr, copper-Cu, iron-Fe, nickel-Ni, lead-Pb, zinc-Zn] concentration and GATA3,CK5,CK6, by ICP-OES and RT-PCR, respectively. Also, histopathology and immunohistochemistry for GATA3/CK5/6 were performed. RESULTS: Stage was pT1/pT2/pT3/pT4 in 36/17/75/15 and grade was G1/G2/G3 in 26/32/85 patients, respectively. High Cd, Co, Cr, Ni, and/or Pb concentration in BC tissue was associated with high CK5/6 and lower GATA3 expression. High GATA3 was associated with low stages, low grade and negative lymph nodes (LN), while high CK5/6 expression was associated with the reverse. Cu had antagonistic effects to (Cd, Co, Cr, Ni, Pb) regarding both markers. No significant association was found between Fe or Zn and GATA3or CK5/6 expression. CONCLUSIONS: High BC tissue concentration of Cd, Co, Cr, Ni, and/or Pb has been proved to be associated with high expression of the basal Cytokeratin 5/6 and lower expression of luminal marker GATA3. High GATA3 and CK5/6 expression are associated with favorable (low stages, low grade, negative LN) and aggressive BC, respectively. However, data on cancer specific survival are awaited.