Immunohistochemical expression of EGFR, HB-EGF, CD9 and MAPK in superficial bladder cancer could be marker for recurrence and progression.
M.I.Toma1, U.Sommer1, M.O.Grimm2, S. Füssel2, M.P.Wirth2, G.B.Baretton1
1 Institut für Pathologie, Universitätsklinikum Carl Gustav Carus, Dresden
2 Klinik und Poliklinik für Urologie, Universitätsklinikum Carl Gustav Carus, Dresden
Aims: This study explores the expression of EGFR, HB-EGF, MAPK and CD9 in superficial and invasive bladder cancer (BCa) and its correlation with recurrence and disease progression.
Methods: Tissue microarrays from archival material from 117 patients undergoing transurethral resection or cystoprostatectomy for superficial BCa were included in the study. 55 patients showed no recurrence or progression after transurethral resection, 45 patients showed recurrence after first therapy and 17 patients showed disease progression. The immunohistochemistry was done by incubation with mono- and polyclonal antibodies (EGFR from Fa Dako, HB-EGF from Dr. R. M. Adam, Harvard Medical School, Boston, MAPK from Cell Signaling and CD9 from Fa. Serotec), followed by incubation with Envision Plus (Dako, Denmark). Cytoplasmic expression was evaluated and the cases were separated in negative, weak, moderate or strong staining for EGFR. For CD9 and MAPK intensity of staining and percent of stained cells were noticed. HB-EGF was evaluated as staining intensity of the cytoplasm and percent of stained nuclei. Statistical analysis was done by SPSS 17 for Windows.
Results: Significant correlations were noticed in EGFR, MAPK and CD9 expression patterns in recurrent or progressive BCa comparing with tumors without recurrence or progress. Statistic significant differences were also observed between normal tissue and pTa and pT1 BCa for EGFR expression and between pTa and pT1 BCa for the cytoplasmic HB-EGF expression.
Expression of EGFR and nuclear expression of MAPK correlated with tumor grade. Tumor specific, but not overall survival, is shorter in CD9 negative bladder cancer cases than in CD9 positive cases (log rank test, p=0.015) as well as in tumor with positive cytoplasmic expression for HB-EGF (log rank test, p=0.037).The tumor specific survival is correlated with cytoplasmic as well as with nuclear MAPK expression in bladder cancer (log rank test; p=0.009, p=0.007, respectively). The Spearman correlation showed an association between immunohistochemical expression of CD9, MAPK and HB-EGF.
Conclusions: Expression of EGFR, HB-EGF, CD9 and MAPK are associated with tumor stage and grade in superficial BCa and could predict progression and recurrence, and may play an important role for tumor specific survival in BCa.