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Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to cancer predisposition in hereditary non-polyposis colon cancer

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Abstract

The majority of tumours in patients with hereditary non-polyposis colon cancer (HNPCC) occur in large intestine and endometrium; also, other tissues are at increased risk. We studied expression of hMLH1 and hMSH2 proteins in 148 normal samples of various tissues from non-HNPCC patients and in 14 normal colon tissues from HNPCC patients. Immunohistochemical technique was used. Intensity of nuclear staining, percentage of stained cells and H-scores were calculated. Tissues were divided into groups. Groups A, B and C included tissues with increased risk of cancer in HNPCC A) stomach, small and large bowel; (B) endometrium; (C) ovary, ureter, urinary bladder, kidney and liver. Group D tissues were without increased risk. Expression of the proteins was significantly higher in groups A, B and C compared with group D (P<0.0001, P=0.0004 for hMSH2 in C versus D). The expression was highest in testis. In colons of HNPCC patients, expression of the mutated gene product was significantly lower than in non-HNPCC patients. In conclusion, hMLH1/hMSH2 protein expression is constitutively higher in certain cell types of certain tissues, including the majority of tissues that are at increased risk of cancer in HNPCC. However, association of strong hMLH1/hMSH2 expression with cancer risk is not strictly valid.

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Acknowledgements

This work was supported by Ministry of Health Care of the Czech Republic, grant no. NC/6741–3. I am indebted to reviewers for their helpful comments.

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Authors and Affiliations

  1. Předvrší 560, 725 26 , Ostrava-Krásné Pole, Czech Republic

    Pavlína Plevová

  2. Institute of Pathology and Laboratory of Molecular Pathology, Medical Faculty of the Palacký University, Hněvotínská 3, 775 15 , Olomouc, Czech Republic

    Pavlína Plevová, Eva Sedláková, Petra Skýpalová & Zdeněk Kolář

  3. Department of Medical Genetics, University Hospital of Ostrava, tř. 17.listopadu 1790, 708 52 , Ostrava, Czech Republic

    Pavlína Plevová

  4. Institute of Biophysics and Statistics, Palacký University, Hněvotínská 3, 775 15 , Olomouc, Czech Republic

    Jana Zapletalová

  5. Institute of Genetics, Faculty Hospital, V úvalu 84, Prague-Motol, Czech Republic

    Anna Křepelová

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  1. Pavlína Plevová
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Correspondence to Pavlína Plevová.

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Plevová, P., Sedláková, E., Zapletalová, J. et al. Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to cancer predisposition in hereditary non-polyposis colon cancer. Virchows Arch 446, 112–119 (2005). https://doi.org/10.1007/s00428-004-1139-5

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  • DOI: https://doi.org/10.1007/s00428-004-1139-5

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