The role of cell cycle regulatory proteins in the pathogenesis of melanoma

Li, Wei; Sanki, Amira; Karim, Rooshdiya Z.; Thompson, John F.; Lee, C. Soon; Zhuang, Liqing; McCarthy, Stanley W.; Scolyer, Richard A.

doi:10.1080/00313020600817951

Cited by 123 publications

(184 citation statements)

References 160 publications

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“…In agreement with our results, p21 levels are usually low or undetectable in the majority of cutaneous nevi, with greater expression in primary melanomas [8,21,22]. The exact mechanism causing the increased expression of p21 in primary melanomas is unclear, although possible hypotheses include microenvironmental signals, checkpoint adaptation, p21 mutations, altered or inhibited p21 binding to cyclin/cdk complexes and abnormal protein degradation [5]. On the other hand, the expression of p21 is lower in melanoma metastases when compared with the corresponding primary lesions in most studies [20,22].…”

Section: Discussionsupporting

confidence: 87%

“…In agreement with these results, cutaneous nevi have been shown to be uniformly positive for p16 in more than 70% of cells [7,15]. On the other hand, loss of p16 expression has also been demonstrated in almost 50% of primary cutaneous and oral melanomas, similarly to many other cancers, including pancreatic, esophageal, lung, head and neck, breast, bladder, brain and ovarian [1,5,13,14]. Although there is general consensus regarding the loss of p16 expression in cutaneous melanomas, it is suggested that this occurs in later stages of the disease, as it is not altered in melanoma in situ [16].…”

Section: Discussionsupporting

confidence: 69%

“…However, these findings may not be applied to oral melanomas, because we found reduced p16 expression also in oral in situ melanomas, suggesting that this alteration may be relevant in the initial phases of oral melanoma development. In oral nevi, expression of p16 was not altered, indicating that in the mouth, nevi do not precede melanoma formation [5]. Reduced expression of p16 in cutaneous melanomas is also associated with a significant risk of recurrence and it is considered an independent predictor for decreased patient survival [13,17,18].…”

Section: Discussionmentioning

confidence: 99%

“…p27 was strongly expressed in all nevi cells, in contrast to oral melanomas where six out of 13 cases were weakly or moderately positive. High expression of p27 is a feature of benign lesions, and it can be used to distinguish benign and malignant tumors [5]. Strong p27 nuclear staining has been shown in cutaneous nevi, including Spitz nevi [9,19], and its expression is progressively lost during the development of melanomas [9,13,19].…”

Section: Discussionmentioning

confidence: 99%

“…Although most primary oral melanomas appear as new lesions from apparently normal mucosa, about 30-50% are preceded by oral pigmentation for several months or even years. The transformation of melanocytes to melanoma cells involves abnormal cell proliferation associated with alterations in the cell cycle regulatory mechanisms, such as inactivation of cyclindependent kinases (cdk) [4,5].…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

Andrade

León

Carlos³

et al. 2012

Head and Neck Pathol

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The acquisition of abnormalities at G1/S is considered a crucial step in the genesis and progression of melanoma. The expression of cell cycle regulators has also been used in various neoplasms as an adjunct to diagnosis. The aim of this study was to compare the expression of p16, p21, p27 and cyclin D1 in oral nevi and melanomas. Expression of these cell cycle regulatory proteins was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas. p16 and p27 were highly expressed in intramucosal nevi, whereas p21 and cyclin D1 expression was higher in oral melanomas. The results indicate that p21 and cyclin D1 may be involved in the development of oral melanomas, and eventually they may be useful in the differential diagnoses of oral benign and malignant melanocytic lesions.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

Andrade

León

Carlos³

et al. 2012

Head and Neck Pathol

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Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy alone

Chung¹,

Lee²,

Horng

et al. 2008

Head & Neck

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Background. Environmental exposures to tobacco, alcohol, human papillomavirus (HPV) and/or Epstein-Barr virus (EBV), all of which can perturb multiple cell cycle proteins or tumor suppressors, have been implicated in the pathogenesis of different subsets of head and neck cancers. The aim of this study was to investigate to which extent the virus infection by itself, and/or the altered cell cycle proteins, contributes to prognosis in locally advanced tonsillar squamous cell carcinomas (TSCCs) treated with concurrent chemoradiotherapy (CCRT) alone.Methods. Serial tumor tissue arrays from archival samples were tested for the presence of HPV genome integration or EBV episome by means of DNA sequencing, realtime polymerase chain reaction (PCR), and in situ hybridization. Alterations of cell cycle proteins (p53, pRb, and p21) were evaluated by immunohistochemical staining. The association of viral presence with altered cell cycle proteins was correlated to clinical outcomes.Results. Of the 46 patients with the same T2N2bM0 stage IVA among consecutive patients with TSCC, 23 (50%) had integrated HPV DNA and only 1 (2%) had EBV episome. The HPV types detected were almost all HPV-16. A reduced expression pattern of p53, pRb, and p21 was noted in HPVpositive tumors, and the incremental number of alterations in the 3 proteins was significantly associated with HPV-negative tumors. The presence or absence of HPV together with the number of altered expression of the 3 cell cycle markers resulted in further identification of 4 biologically and clinically distinct subgroups with different outcomes after CCRT.Conclusions. Use of combined biomarkers of oncogenic HPV and tumor suppressors of p53, pRb, and p21 in advanced TSCC provides prognostic molecular classification superior to the TNM stage system and identifies low-risk patients for organ preservation by CCRT alone and high-risk patients who might benefit from planned tonsillectomy and neck dissection before

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Anti‐proliferative effect of curcumin on melanoma cells is mediated by PDE1A inhibition that regulates the epigenetic integrator UHRF1

Abusnina

Keravis

Yougbaré

et al. 2011

Molecular Nutrition Food Res

107

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The role of cell cycle regulatory proteins in the pathogenesis of melanoma

Cited by 123 publications

References 160 publications

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy alone

Anti‐proliferative effect of curcumin on melanoma cells is mediated by PDE1A inhibition that regulates the epigenetic integrator UHRF1

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