Full-text resources of PSJD and other databases are now available in the new Library of Science.
Visit https://bibliotekanauki.pl

PL EN


Preferences help
enabled [disable] Abstract
Number of results
2002 | 49 | 2 | 377-385

Article title

Expression of p16 in sporadic primary uveal melanoma.

Content

Title variants

Languages of publication

EN

Abstracts

EN
Expression of p16 protein, intragenic mutations of CDKN2A and hypermethylation of CDKN2A promoter region in 41 sporadic primary uveal melanomas were studied. There were 2 cases of spindle cell B histological type, 11 of A + B and 28 of mixed type. All melanomas infiltrated sclera but in 28 cases infiltration was superficial while in 13 profound. In 7 cases the tumor infiltrated the optic nerve. Expression of p16 was studied by immunohistochemistry and recorded by assessment of the proportion of positive tumor cells and staining intensity. Results were expressed as staining index (IRS). Intragenic mutations were studied by PCR-SSCP followed by sequencing, while hypermethylation of the promoter region by CpG methylation assay. In 15% of cases less than 10% of melanoma cells were p16 positive, in 70% of cases less than 50% of cells, while in 7% more than 80% of cells stained for p16 (mean IRS for all cases was 4.87 ± 2.43). In B type the IRS was 8.5 ± 0.7, in A + B type 6.0 ± 2.1 and in the mixed type 4.17 ± 2.43 (differences statistically significant). In melanomas profoundly infiltrating sclera mean IRS was 4.16, while in those infiltrating optic nerve 3.71 (statistically not significant). Analysis of the intragenic mutations revealed in two patients a GAC/GAT substitution in codon 84 - a silent mutation. No hypermethylation of the CpG island of the p16 promoter region was found. In conclusion, we found that the degree of p16 expression is related to the histological type of tumor but not to the histological indicators of tumor invasiveness and that intragenic mutations and promoter hypermethylation are not major mechanisms of p16 inactivation in sporadic uveal melanoma.

Year

Volume

49

Issue

2

Pages

377-385

Physical description

Dates

published
2002
received
2002-04-22
revised
2002-05-23
accepted
2002-06-2

Contributors

  • Department of Cancer Immunology, University School of Medical Sciences and GreatPoland Cancer Center, Poznań, Poland
  • Department of Cancer Immunology, University School of Medical Sciences and GreatPoland Cancer Center, Poznań, Poland
  • Department of Cancer Immunology, University School of Medical Sciences and GreatPoland Cancer Center, Poznań, Poland
  • Department of Cancer Immunology, University School of Medical Sciences and GreatPoland Cancer Center, Poznań, Poland
  • Department of Ophtalmology, College of Medicine, Jagiellonian University, Kraków, Poland
  • Department of Ophtalmology, College of Medicine, Jagiellonian University, Kraków, Poland
  • Department of Ophtalmology, College of Medicine, Jagiellonian University, Kraków, Poland
  • Department of Clinical and Experimental Pathomorphology, College of Medicine, Jagiellonian University, Kraków, Poland
  • Department of Cancer Immunology, University School of Medical Sciences and GreatPoland Cancer Center, Poznań, Poland

References

  • Brantly MA, Harbour JW. (2000) Inactivation of retinoblastoma protein in uveal melanoma by phosphorylation of sites in the COOH-terminal region. Cancer Res.; 60: 4320-3.
  • Cairns P, Polascik TJ, Eby Y, et al. (1995) Frequency of homozygous deletion at p16/ CDKN2 in primary human tumours. Nat Genet.; 11: 210-2.
  • Coupland SE, Bechrakis N, Schuler A, et al. (1998) Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma. Br J Ophthalmol.; 82: 961-70.
  • Flores FF, Graeme JW, Glendending JM. (1996) Loss of the p16INK4a and p15INK4b genes, as well as neighboring 9p21 markers, in sporadic melanoma. Cancer Res.; 58: 5023-32.
  • Fountain JW, Bale SJ, Housman DE, Dracopoli NC. (1990) Genetics of melanoma. Cancer Surv.; 9: 645-71.
  • Funk JO, Schiller PI, Barrett MT, Wong DJ, Kind P, Sander CA. (1998) P16INK4a expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma. J Cutan Pathol.; 25: 291-6.
  • Garner A, Klintworth GK. (1994) Pathobiology of ocular disease: a dynamic approach. Marcel Dekker Inc., New York.
  • Grover R, Chana JS, Wilson GD, Richman PI, Sanders R. (1998) An analysis of p16 protein expression in sporadic malignant melanoma. Melanoma Res.; 8: 267-72.
  • Hara F, Smith R, Parry D, Tahara H, Stone S, Peters G. (1996) Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol Cell Biol.; 16: 859-67.
  • Herman JG, Merlo A, Mao L, et al. (1995) Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res.; 55: 4525-30.
  • Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A.; 93: 9821-6.
  • Holuska FG, Hodi, FS. (1998) Molecular genetics of familial cutaneous melanoma. J Clin Oncol.; 16: 670-82.
  • Kamijo T, Zindy F, Roussel MF, et al. (1997) Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell.; 91: 649-59.
  • Keller-Melchior R, Schmidt R, Piepkorn M. (1998) Expression of the tumor suppressor gene product p16 INK4a in benign and melanocytic lesions. J Invest Dermatol.; 110: 932-8.
  • Liu Q, Neuhausen S, McClure M, et al. (1995) CDKN2 (MTS1) tumor suppressor gene mutations in human cell lines. Oncogene.; 10: 1061-7.
  • Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H. (1998) Mutation of p16 and p15 tumor supressor genes and replication errors contribute independently to the pathogenesis of sporadic malignant melanoma. Arch Dermatol Res.; 290: 175-80.
  • McLean IW, Foster WD, Zimmerman LE, et al. (1983) Modifications of Callender's classification of uveal melanoma at the Armed Forces Institute of Pathology. Am J Ophthalmol.; 96: 502-9.
  • Merbs SL, Sidranski D. (1999) Analysis of p16 (CDKN2/MTS-1/INK4A) alternations in primary sporadic uveal melanoma. Invest. Ophthalmol Vis Sci.; 40: 779-83.
  • Morita R, Fujimoto A, Hatta N, Takehara K, Takata M. (1998) Comparison of genetic profiles between primary melanomas and their metastases reveals alternation and clonal evolution during progression. J Invest Dermatol.; 111: 919-24.
  • Ohta M, Berd D, Shimizu M, et al. (1996) Deletion mapping of chromosome region 9p21-22 surrounding the CDKN2 locus in melanoma. Int J Cancer.; 65: 762-7.
  • Peng HQ, Bailey D, Bronson D, Goss PE, Hogg D. (1995) Loss of heterozygosity of tumor suppressor genes in testis cancer. Cancer Res.; 55: 2871-5.
  • Reed JA, Loganzo F, Shea CR, et al. (1995) Loss of expression of p16/cyclin-dependent kinase inhibitor 2 tumor suppression gene in melanocytic lesion correlates with invasive stage of tumor progression. Cancer Res.; 55: 2713-8.
  • Remmele W, Stegner HE. (1987) Vorschlag zür Einheitlichen Definition eines ImmunoReaktiven Score (IRS) für dem ImmunoHistochemischen Ostrogenrezeptor - Nachweis (ER-ICA) im MammakarZinomgeweke. Pathologe.; 8: 138-40.
  • Ruiz A, Puig S, Lynch M, Castel T, Estivill X. (1998) Retention of the CDKN2A locus and low frequency of point mutations in primary and metastatic cutaneous malignant melanoma. Int J Cancer.; 76: 312-6.
  • Smith-Sorensen B, Hoving E. (1996) CDKN2(p16INK4a) somatic and germline mutations. Hum Mutat.; 7: 294-03.
  • Sparrow LE, Eldon MJ, English DR, Heenan PJ. (1998) p16 and p21 WAF1 protein expression in melanocytic tumors by immunohistochemistry. Am J Dermatopathol.; 20: 255-61.
  • Strume O, Akslen LA. (1997) Alternation and prognostic significance of p16 and p53 protein expression in subgroups of cutaneous melanoma. Int J Cancer.; 74: 535-9.
  • Wagner SN, Wagne, C, Briedigkeit L, Goos M. (1998) Homozygous deletion of the p16 INK4a and p15 INK4b tumour suppressor genes in subset of human sporadic malignant melanoma. Br. J Dermatol.; 138: 13-21.

Document Type

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.bwnjournal-article-abpv49i2p377kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.