p16INK4a is a Prognostic Marker in Resected Ductal Pancreatic Cancer

Gerdes, Berthold; Ramaswamy, Annette; Ziegler, Andreas; Lang, Sven A.; Kersting, Michael; Baumann, Renate; Wild, Anja; Moll, Roland; Rothmund, M.; Bartsch, Detlef K.

doi:10.1097/00000658-200201000-00007

Cited by 86 publications

(59 citation statements)

References 38 publications

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“…We believe that the significantly larger number of tumors in the current series, 77 tumor samples from 64 patients, provided superior statistical power to demonstrate progressive loss of p16 with tumor progression, unlike previous reports [5]. Similar to pancreatico-biliary [25,26], hepatocellular [27], colorectal [28], and non-small cell lung carcinomas [29], we found that MM that retained p16 expression had longer overall and disease specific survival but this did not reach significance.…”

Section: Discussioncontrasting

confidence: 69%

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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Section: Discussioncontrasting

confidence: 69%

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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“…5,6 Moreover, recent studies have extensively demonstrated that the inactivation of p16 INK4A in the members of the INK4 family leads to the development and aggression of a number of human malignancies including HCC. [7][8][9][10][11] These previous studies suggested that the other INK4 family might also play a role in the progression and prognosis of human cancers. Recently, inactivation of p18 INK4C has been reported in various human cancers.…”

Section: Discussionmentioning

confidence: 96%

Reduced expression of cell cycle regulator p18INK4C in human hepatocellular carcinoma

et al. 2004

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“…In our study, the loss of p16 expression was detected in 32 of 51 (62.7%) patients with gallbladder cancer. In addition, the loss of p16 expression has been correlated with tumor progression or with decreased survival among patients with carcinoma of the lung, pancreas and esophagus, and malignant melanoma [21,22,24] . The correlation between p16 expression and clinicopathological factors is controversial.…”

Section: Discussionmentioning

confidence: 99%

Two distinct pathways of p16 gene inactivation in gallbladder cancer

Hiroyuki¹

2007

WJG

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AIM:To examine the mechanism of inactivation of the p16 gene in gallbladder cancer, and to investigate p16 alterations and their correlation with clinicopathological features. METHODS:Specimens were collected surgically from 51 patients with gallbladder cancer. We evaluated the status of protein expression, loss of heterozygosity (LOH), homozygous deletion and promoter hypermethylation using immunohistochemistry, microsatellite analysis, quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR, respectively. In addition, mutations were examined by direct DNA sequencing. RESULTS:Homozygous deletions of the p16 gene exon2, LOH at 9p21-22, p16 promoter hypermethylation, and loss of p16 protein expression were detected in 26.0% (13/50), 56.9% (29/51), 72.5% (37/51) and 62.7% (32/51), respectively. No mutations were found. LOH at 9p21 correlated with the loss of p16 protein expression (P < 0.05). Homozygous deletion of the p16 gene, a combination LOH and promoter hypermethylation, and multiple LOH at 9p21 were significantly correlated with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13) of the tumors with homozygous deletion of the p16 gene, respectively. P16 alterations were not associated with clinicopathological features. CONCLUSION:Our results suggest that LOH and homozygous deletion may be two distinct pathways in the inactivation of the p16 gene. Homozygous deletion, a combination of LOH and promoter hypermethylation, and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer.

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p16INK4a is a Prognostic Marker in Resected Ductal Pancreatic Cancer

Cited by 86 publications

References 38 publications

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

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

Reduced expression of cell cycle regulator p18INK4C in human hepatocellular carcinoma

Two distinct pathways of p16 gene inactivation in gallbladder cancer

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