Identification of Bladder Cancer Patients at Risk for Recurrence or Progression: An Immunohistochemical Study Based on the Expression of Metallothionein

Identification of Bladder Cancer Patients at Risk for Recurrence or Progression: An Immunohistochemical Study Based on the Expression of Metallothionein

Despite similarities in tumor stage and grade the individual outcome of bladder cancer patients is not predictable. The ideal tool for treatment stratification has not yet been found. Metallothionein (MT) overexpression is correlated with poor tumor differentiation, resistance to chemotherapy, and i...

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Published in:Journal of Toxicology and Environmental Health, Part A Vol. 71; no. 13-14; pp. 954 - 959
Main Authors: Hinkel, Andreas, Schmidtchen, Sonja, Palisaar, Rein-Jueri, Noldus, Joachim, Pannek, Jürgen
Format: Journal Article
Language:English
Published: England Taylor & Francis Group 01-01-2008
Subjects:
Adult
Aged
Aged, 80 and over
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic - physiology
Humans
Immunohistochemistry
Male
Metallothionein - genetics
Metallothionein - metabolism
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Prognosis
Retrospective Studies
Risk Factors
Urinary Bladder Neoplasms - mortality
Urinary Bladder Neoplasms - pathology
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Summary:Despite similarities in tumor stage and grade the individual outcome of bladder cancer patients is not predictable. The ideal tool for treatment stratification has not yet been found. Metallothionein (MT) overexpression is correlated with poor tumor differentiation, resistance to chemotherapy, and impaired survival in different malignancies. The clinical relevance of MT expression for defining patients at high risk for recurrence or progression was assessed. MT was detected immunohistochemically and evaluated semiquantitively in tumor specimens of 103 male and 19 female patients (transsurethral resection: n = 94, cystectomy: n = 28). Mean age of the patients was 68 (38-87) yr. According to histopathological features, three groups were distinguished for further analysis (pTa-1G1-2, pTis/pT1G3, and muscle invasive tumors). A cutoff value of 50% immunoreactive cells was used for further analysis. The 5-yr tumor specific survival rate was significantly lower in patients with high MT expression (32 vs. 72%). Accordingly, impaired 5-yr recurrence (90 vs. 58%), and progression rates (78 vs. 54%) were associated with high MT expression. All patients suffering from pTis and pT1G3 tumors with MT expression above the cutoff value showed recurrence within less than 40 mo, whereas 26% of those patients with MT expression below the cutoff value remained long-term recurrence free. Long term progression free survival was detected in 75% of pT1G3 patients with MT expression below the cutoff value. In contrast, 68% of pT1G3 tumor patients with MT expression above the cutoff value progressed, all within the first 12 mo after initial tumor resection. A correlation between high MT expression and prognosis was demonstrated especially in pT1G3 and pTis tumors, where >50% MT expression was linked to shorter tumor-specific survival and increased recurrence/progression rates. Thus, MT expression seems to be a promising marker for further risk stratification in the clinical treatment of bladder cancer patients.
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ISSN:1528-7394
1087-2620
DOI:10.1080/15287390801989101