A subclass of HER1 ligands is a prognostic marker for survival in bladder cancer patients

Members of the epidermal growth factor (EGF) family have been suggested as prognostic markers in patients with bladder cancer. Thus far, there has bee n no consensus on their usefulness. We report an analysis of six ligands an d two receptors of which a subset correlate to tumor stage and survival. Biopsies from bladder cancer tumors were obtained from 73 patients followed for a median of 28 months. The mRNA content for six ligands [EGF, transfor ming growth factor alpha (TGF-alpha), amphiregulin (AR), beta-cellulin (bet a CL), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EPI)] a nd two receptors [EGF receptor I Human EGF Receptor (HER1) and 2 (HER2)] wa s examined by a newly developed quantitative reverse transcription-PCR meth od. Five ligands and two receptors (HER1 and HER2) were present in median conce ntrations of (10(-21) mol/mug RNA) 0.39 (AR), 11 (beta CL), 2.4 (EPI), 40 ( HB-EGF), 1.4 (TGF-alpha), 75 (HER1), and 39,000 (HER2. EGF was barely detec table. A significantly higher expression of EPI (P < 0.001), HB-EGF (P < 0. 001), and TGF-alpha (P < 0.05) were observed in T2-T4 tumors as compared wi th T alpha tumors. Especially the expression of EPI mRNA correlated strongl y to survival (P < 0.0005), but increased expression of TGF-alpha (P < 0.00 5), AR, and HB-EGF (P < 0.02) was also associated with a reduced life span. For the first time, mRNA expression of six ligands and two receptors of the EGF family have been examined in bladder cancer tumors. Our data emphasize that members of the EGF family, especially EPI, may be potential bladder t umor markers.