p16(INK4a) expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma

Jens Oliver Funk, Peter I. Schiller, Michael Barrett, David J. Wong, Peter Kind, Christian A. Sander

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

The product of the p16/INK4a/CDKN2/MTS1 tumor-suppressor gene acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein. p16 is inactivated in a wide range of human malignancies, including familial melanoma. However, its expression and function in sporadic melanoma has not been extensively investigated. We studied p16 expression in 62 archival melanomas and 30 archival nevi and lentigines by immunohistochemistry. Eighteen of 26 (69%) superficial spreading melanomas, 17 of 28 (61%) nodular melanomas, all of three lentigo maligna melanomas, and all of five melanoma metastases were found to harbor less than 10% p16-positive tumor cells. In contrast, only six of 24 (25%) nevi had less than 10% positive cells. No correlation between tumor thickness and loss of p16 expression was found. Using DNA from micro-dissected tumor and matched normal tissues, five of seven (71%) p16-negative melanoma cases had 9p21 loss of heterozygosity (LOH), and one of these 9p21 LOH cases had promoter region hypermethylation of the remaining p16 allele. These data demonstrate that partial or complete loss of p16 expression is prevalent in sporadic melanoma and is frequently associated with 9p21 LOH.

Original languageEnglish (US)
Pages (from-to)291-296
Number of pages6
JournalJournal of Cutaneous Pathology
Volume25
Issue number6
DOIs
StatePublished - 1998
Externally publishedYes

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Loss of Heterozygosity
Melanoma
Nevus
Neoplasms
Hutchinson's Melanotic Freckle
Lentigo
Retinoblastoma Protein
Cyclin-Dependent Kinases
Tumor Suppressor Genes
Genetic Promoter Regions
Cell Cycle
Immunohistochemistry
Alleles
Neoplasm Metastasis
DNA

ASJC Scopus subject areas

  • Dermatology
  • Pathology and Forensic Medicine

Cite this

p16(INK4a) expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma. / Funk, Jens Oliver; Schiller, Peter I.; Barrett, Michael; Wong, David J.; Kind, Peter; Sander, Christian A.

In: Journal of Cutaneous Pathology, Vol. 25, No. 6, 1998, p. 291-296.

Research output: Contribution to journalArticle

Funk, Jens Oliver ; Schiller, Peter I. ; Barrett, Michael ; Wong, David J. ; Kind, Peter ; Sander, Christian A. / p16(INK4a) expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma. In: Journal of Cutaneous Pathology. 1998 ; Vol. 25, No. 6. pp. 291-296.
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abstract = "The product of the p16/INK4a/CDKN2/MTS1 tumor-suppressor gene acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein. p16 is inactivated in a wide range of human malignancies, including familial melanoma. However, its expression and function in sporadic melanoma has not been extensively investigated. We studied p16 expression in 62 archival melanomas and 30 archival nevi and lentigines by immunohistochemistry. Eighteen of 26 (69{\%}) superficial spreading melanomas, 17 of 28 (61{\%}) nodular melanomas, all of three lentigo maligna melanomas, and all of five melanoma metastases were found to harbor less than 10{\%} p16-positive tumor cells. In contrast, only six of 24 (25{\%}) nevi had less than 10{\%} positive cells. No correlation between tumor thickness and loss of p16 expression was found. Using DNA from micro-dissected tumor and matched normal tissues, five of seven (71{\%}) p16-negative melanoma cases had 9p21 loss of heterozygosity (LOH), and one of these 9p21 LOH cases had promoter region hypermethylation of the remaining p16 allele. These data demonstrate that partial or complete loss of p16 expression is prevalent in sporadic melanoma and is frequently associated with 9p21 LOH.",
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T1 - p16(INK4a) expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma

AU - Funk, Jens Oliver

AU - Schiller, Peter I.

AU - Barrett, Michael

AU - Wong, David J.

AU - Kind, Peter

AU - Sander, Christian A.

PY - 1998

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