TY - JOUR

T1 - A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients

AU - Thøgersen, Helle-Merete Vissing

AU - Sørensen, B S

AU - Poulsen, S S

AU - Orntoft, T F

AU - Wolf, H

AU - Nexo, E

AU - Poulsen, Steen Seier

PY - 2001/8/15

Y1 - 2001/8/15

N2 - Members of the epidermal growth factor (EGF) family have been suggested as prognostic markers in patients with bladder cancer. Thus far, there has been no consensus on their usefulness. We report an analysis of six ligands and 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, transforming growth factor alpha (TGF-alpha), amphiregulin (AR), betacellulin (betaCL), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EPI)] and two receptors [EGF receptor I Human EGF Receptor (HER1) and 2 (HER2)] was examined by a newly developed quantitative reverse transcription-PCR method. Five ligands and two receptors (HER1 and HER2) were present in median concentrations of (10(-21) mol/microg RNA) 0.39 (AR), 11 (betaCL), 2.4 (EPI), 40 (HB-EGF), 1.4 (TGF-alpha), 75 (HER1), and 39,000 (HER2). EGF was barely detectable. 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 with Ta tumors. Especially the expression of EPI mRNA correlated strongly to survival (P <0.0005), but increased expression of TGF-alpha (P <0.005), 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 tumor markers.

AB - Members of the epidermal growth factor (EGF) family have been suggested as prognostic markers in patients with bladder cancer. Thus far, there has been no consensus on their usefulness. We report an analysis of six ligands and 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, transforming growth factor alpha (TGF-alpha), amphiregulin (AR), betacellulin (betaCL), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EPI)] and two receptors [EGF receptor I Human EGF Receptor (HER1) and 2 (HER2)] was examined by a newly developed quantitative reverse transcription-PCR method. Five ligands and two receptors (HER1 and HER2) were present in median concentrations of (10(-21) mol/microg RNA) 0.39 (AR), 11 (betaCL), 2.4 (EPI), 40 (HB-EGF), 1.4 (TGF-alpha), 75 (HER1), and 39,000 (HER2). EGF was barely detectable. 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 with Ta tumors. Especially the expression of EPI mRNA correlated strongly to survival (P <0.0005), but increased expression of TGF-alpha (P <0.005), 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 tumor markers.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Epidermal Growth Factor

KW - Female

KW - Glycoproteins

KW - Growth Substances

KW - Humans

KW - Immunohistochemistry

KW - Intercellular Signaling Peptides and Proteins

KW - Ligands

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Prospective Studies

KW - RNA, Messenger

KW - Receptor, Epidermal Growth Factor

KW - Receptor, erbB-2

KW - Transforming Growth Factor alpha

KW - Tumor Markers, Biological

KW - Urinary Bladder Neoplasms

M3 - Journal article

C2 - 11507076

VL - 61

SP - 6227

EP - 6233

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 16

ER -