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Regular Article| Volume 95, ISSUE 7, P588-593, July 2001

p53, p21 and metallothionein immunoreactivities in patients with malignant pleural mesothelioma: correlations with the epidemiological features and prognosis of mesotheliomas with environmental asbestos exposure

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      Abstract

      The aim of this study is to investigate immunoreactivity for p53, p21 and metallothionein in diffuse malignant pleural mesothelioma (DMPM) and to determine the relationships between the age, sex, asbestos exposure time, survival of DMPM patients with environmental asbestos exposure and immunoreactivity to p53, p21 and metallothionein.
      Sixty-seven histopathologically-confirmed DMPMs, 38 of whom had environmental and 29 had occupational asbestos exposure, were included. The tumour tissue samples were immunostained with antibodies against p53, p21 and metallothionein. Epidemiological data and the survival times for the DMPM patients with environmental asbestos exposures were obtained from hospital records. Thirty-three per cent of the DMPMs were positive for p53, 35% for p21 and 52% for metallothionein. There was no statistical difference between the histological subtypes of DMPM in terms of immunoreactivity for p53, p21 and metallothionein. For p21 and metallothionein there was a statistically significant difference between the exposure characteristics: patients with environmental asbestos exposure had shown more immunopositivity. There were statistically significant differences between age groups and between asbestos exposure times for metallothionein, and between asbestos exposure times and p21. The patients with positive immunostaining had longer exposure times and were older than those having negative immunostaining. The differences between survival of the patients were not statistically significant in terms of the immunohistochemical results for p53, p21 and metallothionein.

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      References

      References

        • Bignon J
        Overview of current issues with respect to mesothelioma.
        Eur Respir Rev. 1993; 3: 12-17
        • Light RW
        Tumours of the pleura.
        in: Murray JF Nadel JA Testbook of Respiratory Medicine. 2. W.B. Saunders, Philedelphia1994: 2222-2234
        • Tammilehto L
        • Tuomi T
        • Tiainen M
        Malignant mesothelioma: clinical characteristics, asbestos minerology and chromosomal absormalities of 42 patients.
        Eur J Cancer. 1992; 28: 1373-1379
        • Bielefeldt-Ohmann H
        • Jarnicki AG
        • Fitzpatrick DR
        Molecular pathobiology and immunology of malignant mesothelioma.
        J Pathol. 1996; 178: 369-378
        • Craighead JE
        • Kane AB
        The pathogenesis of malignant and nonmalignant serosal lesions in body cavities cosequent to asbestos exposure.
        in: Jauren MC Bignon J Mesothelial Cell and Mesothelioma. Marcel Dekker, New York1994: 79-101
        • Kern JA
        • McLennan G
        Genetic and molecular changes of human lung cancer.
        in: Fishman AP Fisherman's Pulmonary Diseases and Disorders. 2. McGraw Hill, New York1998: 1695-1705
        • Hunchareck M
        Genetic factors in the aetiology of malignant mesothelioma.
        Eur J Cancer. 1995; 31: 1741-1747
        • Cote RJ
        • Jhanwar SC
        • Novick S
        Genetic alterations of the p53 gene are a feature of malignant mesothelioma.
        Cancer Res. 1991; 51: 5410-5416
        • Knuutila S
        • Tammilehto L
        • Mattson K
        Chromosomal abnormalities in human malignant mesothelioma.
        in: Jauren MC Bignon J Mesothelial Cell and Mesothelioma. Marcel Dekker, New York1994: 245-253
        • Metintas M
        • Özdemir N
        • Hillerdal G
        Environmental asbestos exposure and malignant pleural mesothelioma.
        Respir Med. 1999; 93: 349-355
        • Mayall FG
        • Goddard H
        • Gibbs AR
        p53 immunostaining in the distinction between benign and malignant mesothelial proliferation using formalin-fixed paraffin sections.
        J Pathol. 1992; 168: 377-381
        • Levine AJ
        • Momand J
        • Finlay CA
        The p53 tumour supressor gene.
        Nature. 1991; 351: 453-456
        • Smit EF
        • Groen H JM
        • Splinter T AW
        Prognostic factors in resectable non-small cell lung cancer.
        Thorax. 1996; 51: 638-646
        • Nuorva K
        • Mäkitaro R
        • Huhti E
        p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke.
        Am J Respir Crit Care Med. 1994; 150: 528-533
        • McAllen R
        • Kudzu I
        • Dunhill M
        The relationship of p53 immunostaining to survival in carcinoma of the lung.
        Br J Cancer. 1992; 66: 735-738
        • Harris CC
        • Hollstein M
        Clinical implications of the p53 tumour-supressor gene.
        N Eng J Med. 1993; 329: 1319-1327
        • Mayall FG
        • Goddard H
        • Gibbs AR
        The frequency of p53 immunostaining in asbestos-associated mesotheliomas and non-asbestos associated mesotheliomas.
        Histopathology. 1993; 22: 383-386
        • Cagle PT
        • Brown RW
        • Lebovitz RM
        P53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens.
        Hum Pathol. 1993; 25: 443-448
        • Ramael M
        • Lemmens G
        • Eerdekens C
        Immunoreactivity for p53 protein in malignant mesothelioma and nonneoplastic mesothelium.
        J Pathol. 1992; 168: 371-375
        • Kafiri G
        • Thomas DM
        • Shepard NA
        p53 expression in malignant mesothelioma.
        Histopathology. 1992; 21: 331-334
        • Carbone M
        • Rizzo P
        • Grimley PM
        Simian virus-40 large T antigen binds p53 in human mesotheliomas.
        Nat Med. 1997; 3: 908-912
        • Ramael M
        • Deblier I
        • Eerdekens C
        Immunohistochemical staining of ras oncogene product in neoplastic and non neoplastic mesothelial tissues: immunoreactivity for N-ras and lack of immunohistochemical staining for Ha-ras and K-ras.
        J. Pathol. 1993; 169: 421-424
        • Cristaudo A
        • Vivaldi A
        • Sensales G
        Molecular biology studies on mesothelioma tumour samples: preliminary data on H-ras, p21 and SV40.
        J Environ Pathol Tox Oncol. 1995; 14: 29-34
        • Jasani B
        • Schmid KW
        Significance of metallothionein overexpression in human tumors.
        Histopathology. 1997; 31: 211-214
        • Satoh M
        • Cherian MG
        • Imura N
        Modulation of residence to anticancer drugs by inhibition of metallothionein synthesis.
        Cancer Res. 1994; 54: 5255-5257
        • Osmak M
        Multifactorial molecular mechanisms are involved in resistance of preradiated human cervix carcinoma cells to cis-dichlorodiamminoplatinum (II) and vincristine.
        Neoplasma. 1993; 40: 97-101
        • Satoh M
        • Kloth DM
        • Kadhim SA
        Modulation of both cisplatin nephrotoxicity and drug resistance in murine bladder tumor by controlling metallothionein synthesis.
        Cancer Res. 1993; 53: 1829-1832
        • Giuffre G
        • Barrest G
        • Sturniolo GC
        Immunohistochemical expression of metallothionein in normal human colorectal mucosa, in adenocarcinomas and their associated metastates.
        Histopathology. 1996; 29: 347-354
        • Çöplü L
        • Dumortier P
        • Demir AU
        An epidemiological study in an Anatolian village in Turkey environmentally exposed to tremolite asbestos.
        J Environ Pathol Toxic Oncol. 1996; 15: 177-182
        • Dumortier P
        • Çöplü L
        • De Maertelaer V
        • Emri S
        • Bary I
        • De Vuyst P
        Assessment of environmental asbestos exposure in Turkey by bronchoalveolar lavage.
        Am J Respir Crit Care Med. 1998; 158: 1815-1824