Immunophenotypic analysis of the p53 gene in non‐melanoma skin cancer and correlation with apoptosis and cell proliferation

Journal of the European Academy of Dermatology and Venereology - Tập 19 Số 2 - Trang 180-186 - 2005
A. Stratigos1, Nikiforos Kapranos2, E Petrakou2, A Anastasiadou2, A Pagouni1, E. Christofidou1, Athanasios K. Petridis1, O. Papadopoulos1, Eleni Kokka2, C. Antoniou1, S. Georgala1, A. Katsambas1
1Department of Dermatology, University of Athens, Andreas Sygros Hospital, Athens, Greece
2Department of Molecular Pathology, Amalia Fleming Hospital, Athens, Greece.

Tóm tắt

ABSTRACTBackground   Sunlight precipitates a series of genetic events that lead to the development of skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The p53 tumour suppressor gene, which plays a pivotal role in cell division and apoptosis, is frequently found mutated in sunlight‐induced skin tumours.Objective   To investigate the immunoreactivity of the p53 gene in non‐melanoma skin cancers and to correlate its expression with apoptotic and cell proliferation markers.Methods   We analysed 35 non‐melanoma tumours including 19 BCCs and 16 SCCs from sun‐exposed skin areas. p53 protein expression was studied immunohistochemically using the DO7 monoclonal antibody against wild‐type and mutant p53 forms. The percentage of p53‐immunopositive nuclei was measured by image analysis. Cell proliferation and apoptosis were also assessed by image analysis following Ki‐67 immunostaining and application of the TUNEL method on paraffin sections, respectively.Results   The percentage of p53‐expressing cells varied from 3.5 to 90 in BCCs (median value 54.4%) and from 3.7 to 94 in SCCs (median value 40.3%). The mean value of Ki‐67‐positive cells was comparable in both groups of tumours with a mean value of 40.6% in BCCs and 34.6% in SCCs. Conversely, the TUNEL assay showed sporadic staining of apoptotic cells within the tumours with a mean value of 1.12% in BCCs and 1.8% in SCCs. p53 protein expression was correlated positively with cell proliferation (r = 0.75, P = 0.000001) and negatively with apoptosis (r = −0.23, P = 0.05).Conclusion   p53 immunoreactivity was high in the majority of the skin carcinomas examined and correlated positively with cell proliferation and negatively with apoptosis. The p53 protein overexpression appears to be related to an inactivated protein resulting from mutations of the p53 gene or other unclear molecular mechanisms.

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Tài liệu tham khảo

10.1126/science.1905840

10.1073/pnas.88.22.10124

10.1038/358015a0

10.1038/351453a0

10.1073/pnas.90.9.4216

10.1101/gad.4.1.1

10.1111/1523-1747.ep12475717

10.1111/j.1365-2133.1993.tb11840.x

10.1002/1097-0142(19890415)63:8<1607::AID-CNCR2820630827>3.0.CO;2-1

10.1111/j.1365-2559.1990.tb00788.x

Gorczyca W, 1993, Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynucleotidyl transferase end nick translation assays, Cancer Res, 53, 1945

Gusterson BA, 1991, Expression of p53 in premalignant and malignant squamous cell epithelium, Oncogene, 6, 1179

10.1111/j.1365-2133.1992.tb14866.x

McGregor JM, 1992, Aberrant expression of p53‐tumor suppressor protein in non‐melanoma skin cancer, Br J Dermatol, 127, 566

10.1016/S0190-9622(97)80274-5

Shea CR, 1992, Overexpression of p53 protein in basal cell carcinomas of human skin, Am J Pathol, 141, 25

10.1016/S0959-8049(98)00062-8

Gusterson BA, 1991, Expression of p53 in premalignant and malignant squamous epithelium, Oncogene, 6, 1785

10.1111/1523-1747.ep12321051

Kerschmann RL, 1994, p53 oncoprotein expression and proliferation index in keratoacanthoma and squamous cell carcinoma, Arch Dermatol, 130, 181, 10.1001/archderm.1994.01690020047007

10.1097/00000372-199810000-00006

10.1159/000245947

10.1159/000018216

10.1038/356215a0

10.1002/mc.2940040606

10.1002/path.1711660402

10.1002/path.1711720104

Pruneri G, 1997, MDM‐2 oncoprotein overexpression in laryngeal squamous cell carcinoma: association with wild‐type p53 accumulation, Mod Pathol, 10, 785

10.1006/jmbi.1996.0560

10.1111/j.1600-0560.1992.tb01366.x

10.1073/pnas.93.1.274

Hall PA, 1993, High levels of p53 protein in UV‐irradiated normal human skin, Oncogene, 8, 203

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Journal of the European Academy of Dermatology and Venereology

Tập 19 Số 2

180-186

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