The prognostic value of cyclin D1, p53, and MDM2 protein expression in uveal melanoma

Coupland, Sarah E.; Anastassiou, Gerasimos; Stang, Andreas; Schilling, Hannah; Anagnostopoulos, Ioannis; Bornfeld, Norbert; Stein, Harald

doi:10.1002/(sici)1096-9896(200006)191:2<120::aid-path591>3.0.co;2-p

Cited by 79 publications

(31 citation statements)

References 36 publications

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“…79 This has been observed in longitudinal studies using next-generation sequencing in paired primary and metastatic carcinomas, 89 and warrants further investigation using such techniques in UM. The retinoblastoma tumour suppressor pathway is disrupted in most UM either through: hyperphosphorylation of Rb; elevated expression of cyclin D1; or through methylation and inactivation of the INK4A gene [11][12][13][14][15][16] 2. Self-sufficiency in growth signals Gain of cell cycle stimulator-activation of pathways The PI3K-AKT prosurvival pathway is constitutively activated in UM.…”

Section: The Hallmarks Of Cancermentioning

confidence: 99%

Molecular Pathology of Uveal Melanoma

Coupland

Lake

Damato

2014

Clinical Ophthalmic Oncology

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Like other cancers, uveal melanomas (UM) are characterised by an uncontrolled, clonal, cellular proliferation, occurring as a result of numerous genetic, and epigenetic aberrations. Signalling pathways known to be disrupted in UM include: (1) the retinoblastoma pathway, probably as a result of cyclin D1 overexpression; p53 signalling, possibly as a consequence of MDM2 overexpression; and the P13K/AKT and mitogen-activated protein kinase/extracellular signal-related kinase pathway pathways that are disturbed as a result of PTEN and GNAQ/11 mutations, respectively. Characteristic chromosomal abnormalities are common and include 6p gain, associated with a good prognosis, as well as 1p loss, 3 loss, and 8q gain, which correlate with high mortality. These are identified by techniques such as fluorescence in situ hybridisation, comparative genomic hybridisation, microsatellite analysis, multiplex ligationdependent probe amplification, and singlenucleotide polymorphisms. UM can also be categorised by their gene expression profiles as class 1 or class 2, the latter correlating with poor survival, as do BRCA1-associated protein-1 (BAP1) inactivating mutations. Genetic testing of UM has enhanced prognostication, especially when results are integrated with histological and clinical data. The identification of abnormal signalling pathways, genes and proteins in UM opens the way for target-based therapies, improving prospects for conserving vision and prolonging life.

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Section: The Hallmarks Of Cancermentioning

confidence: 99%

Molecular Pathology of Uveal Melanoma

Coupland

Lake

Damato

2014

Clinical Ophthalmic Oncology

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“…Cyclin D1 is a regulatory subunit of the CDK holoenzymes that control the activation of pRB (Sherr, 1994;Hunter and Pines, 1994). Cyclin D1 has been found to collaborate with oncogenes in cellular transformation (Wang et al, 1994) and the protein levels are frequently elevated in uveal-melanomas (Coupland et al, 2000) and primary melanomas that express the tumor suppressor p16 INK4a (Bales et al, 1999). Cyclin D1 promoter activity and mRNA levels are induced by various growth factors, including epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), integrin-linked kinase (ILK) and HGF/SF (Musgrove et al, 1993;Filmus et al, 1994;Albanese et al, 1995;Allen et al, 1995;Alberch et al, 1995;Shambaugh et al, 1996;Bennett and Tonks, 1997;D'Amico et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte growth factor/scatter factor activates proliferation in melanoma cells through p38 MAPK, ATF-2 and cyclin D1

2002

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“…Abnormalities in the p53 gene/protein have been extensively studied in cutaneous and uveal melanomas [30][31][32]. Gwosdz et al [33] reported p53 mutations in 57-58% of MM suggesting the role of non-UV related mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Regulators of Cell Cycle and Apoptosis, p16INK4a, p53, and bcl-2 in Primary Mucosal Melanomas of the Head and Neck

Prasad

Patel

Shah

et al. 2011

Head and Neck Pathol

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Abnormalities in cell cycle regulation, tumor suppressor gene functions and apoptosis are frequent events in tumorigenesis. Their role in the pathogenesis and prognosis of primary mucosal melanomas (MM) of the upper aerodigestive tract remains unknown. Sixty-four patients (40 men, 24 women, median age 64 years) with MM were included in this study; 32 had tumors in the nasal/paranasal cavities, 28 in the oral cavity and 4 in the pharynx. Archival tissues from 47 initial mucosal tumors, 17 mucosal recurrences, and 13 nodal/distant metastases were subjected to immunohistochemistry using antibodies against p16, p53, and bcl-2. The results were correlated with histological features and survival data. Expressions of p16, p53, and bcl-2 proteins were seen in 25% (N = 19/ 76), 21% (N = 16/76), and 74% (N = 56/76) of all tumors, respectively. bcl-2 expression in the initial tumors was associated with significantly longer overall and disease specific survival (3.3 vs. 1.5 years, P B 0.05). Expression of p16 was increasingly lost, from 32% in initial tumors to 12% in recurrent and 15% in metastatic tumors (P = 0.06). Tumors comprised of undifferentiated cells were significantly more p53 positive than epithelioid or spindle cells (80% vs. 33%, P = 0.02). Expression of these markers did not correlate with necrosis, or vascular and/or deep tissue invasion. Expression of bcl-2 is associated with better survival in MM. Loss of p16 was seen with tumor progression whereas aberrant p53 expression was frequent in undifferentiated tumor cells.

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The prognostic value of cyclin D1, p53, and MDM2 protein expression in uveal melanoma

Cited by 79 publications

References 36 publications

Molecular Pathology of Uveal Melanoma

Molecular Pathology of Uveal Melanoma

Hepatocyte growth factor/scatter factor activates proliferation in melanoma cells through p38 MAPK, ATF-2 and cyclin D1

Prognostic Significance of Regulators of Cell Cycle and Apoptosis, p16INK4a, p53, and bcl-2 in Primary Mucosal Melanomas of the Head and Neck

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