title: Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.
abstract: Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82-17.03) and ovarian tumors (OR 7.83; 1.09-56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03-0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08-2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03-2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47-2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.
authors.affiliation: Department of Pathological Physiology, Masaryk University, Brno, Czech Republic ; Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Jaromir
authors.initials: J
authors.lastname: Gumulec
authors.affiliation: Department of Pathological Physiology, Masaryk University, Brno, Czech Republic ; Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Raudenska
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic ; Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic ; Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
authors.forename: Rene
authors.initials: R
authors.lastname: Kizek
authors.affiliation: Department of Pathological Physiology, Masaryk University, Brno, Czech Republic ; Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Masarik
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D016206:Databases, Bibliographic; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008668:Metallothionein / Q000378:metabolism*; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D008668:Metallothionein