Mismatch repair expression in testicular cancer predicts recurrence and survival

We investigated mismatch repair (MMR) gene expression in testicular cancer as a molecular marker for clinical outcome (recurrence, response to chemotherapy and death) using protein expression and specific genetic alterations associated with the presence or absence of MMR activity. One hundred sixty‐...

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Bibliographic Details
Published in:International journal of cancer 2008-04, Vol.122 (8), p.1774-1777
Main Authors: Velasco, Alfredo, Corvalan, Alejandro, Wistuba, Ignacio I., Riquelme, Erick, Chuaqui, Rodrigo, Majerson, Alejandro, Leach, Fredrick S.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
DNA Mismatch Repair
Gene Expression Regulation, Neoplastic
Gynecology. Andrology. Obstetrics
hMSH2
Humans
Immunohistochemistry
Loss of Heterozygosity
Male
Male genital diseases
Medical sciences
Microsatellite Instability
mismatch repair
MutL Protein Homolog 1
MutS Homolog 2 Protein - genetics
MutS Homolog 2 Protein - metabolism
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - metabolism
Neoplasm Recurrence, Local - mortality
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Platinum Compounds - administration & dosage
Predictive Value of Tests
Retrospective Studies
Survival Analysis
testicular cancer
Testicular Neoplasms - drug therapy
Testicular Neoplasms - genetics
Testicular Neoplasms - metabolism
Testicular Neoplasms - mortality
Tumors
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Summary:We investigated mismatch repair (MMR) gene expression in testicular cancer as a molecular marker for clinical outcome (recurrence, response to chemotherapy and death) using protein expression and specific genetic alterations associated with the presence or absence of MMR activity. One hundred sixty‐two cases of paraffin‐embedded testis cancer specimens were subjected to immunohistochemical analysis using monoclonal antibody for MLH1 and MSH2 MMR proteins and genetic analysis using specific polymorphic markers. The degree of MMR immunoreactivity and genetic instability in the form of loss of heterozygosity (LOH) and/or microsatellite instability (MSI) were determined by comparing matched normal and tumor tissue. The degree of immunohistochemical staining for MMR expression was associated with a shorter time to tumor recurrence, resistance to chemotherapy and death. Furthermore, clinical relapse and cancer specific death was also associated with tumors exhibiting a high degree of MSI, p = 0.01 and 0.04, respectively. In contrast, LOH was not associated with recurrence, resistance to chemotherapy or death. Therefore, MMR expression defines testis cancers with distinct molecular properties and clinical behavior, such that tumors with decreased MMR immunostaining and/or increased frequency of MSI have a shorter time to recurrence and death despite chemotherapy. © 2007 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.23291