Expression ofp16INK4A and alterations of the 9p21-23 chromosome region in non-small-cell lung carcinomas: Relationship with tumor growth parameters and ploidy status

Mariatos, G.; Gorgoulis, Vassilis G.; Zacharatos, Panayotis; Kotsinas, Athanassios; Vogiatzi, Thelxiopi; Rassidakis, George Z.; Foukas, Pericles; Liloglou, T.; Tiniakos, Dina; Angelou, Nikos; Manolis, Evangelos N.; Veslemes, M.; Field, John K.; Kittas, Christos

doi:10.1002/(sici)1097-0215(20000320)89:2<133::aid-ijc6>3.0.co;2-c

Cited by 31 publications

(24 citation statements)

References 24 publications

(35 reference statements)

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“…This is similar to the results reported previously, indicating that biallelic inactivation of the FHIT gene by hypermethylation and LOH led to the loss of its expression 29 . In the present study, the frequency of p16 expression was low, compared with previous studies (37–41.9%) 17,30 . This may be due to the advanced cancer samples used in the present study.…”

Section: Discussioncontrasting

confidence: 83%

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Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung

Awaya

Takeshima²,

Amatya³

et al. 2004

Pathology International

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We investigated the aberrant promoter hypermethylation of p16, p15 and p14 genes and loss of heterozygosity (LOH) at 9p21-22 in 48 cases of adenocarcinoma of the lung. The frequencies of hypermethylation of genes were as follows: p16, 25.0%; p15, 22.9%; and p14, 18.8%. The frequency of LOH at chromosome 9p21-22 was 60.9%. The frequency of two-hit inactivation of the p16 gene by hypermethylation and LOH was 21.7%. Two-hit inactivation of the p16 gene showed loss of protein expression and was significantly correlated with tumor size, tumor grade and the Ki-67 labeling index. Hypermethylation of the p16 gene was not significantly correlated with hypermethylation of the p15 and p14 genes, both of which are close to the p16 gene locus, suggesting that hypermethylation of these genes occurs selectivity. In conclusion, biallelic inactivation of the p16 gene by hypermethylation and LOH might cause loss of p16 expression and play an important role in the development of adenocarcinoma of the lung. Therefore, controlling and monitoring for hypermethylation of the p16 gene may be partially useful for treatment and early diagnosis of adenocarcinoma of the lung.

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Section: Discussioncontrasting

confidence: 83%

“…29 In the present study, the frequency of p16 expression was low, compared with previous studies (37-41.9%). 17,30 This may be due to the advanced cancer samples used in the present study.…”

Section: Discussionmentioning

confidence: 93%

Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung

Awaya

Takeshima²,

Amatya³

et al. 2004

Pathology International

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“…The frequency of LOH at 9p21 in gallbladder carcinoma ranges from 38 to 60% [5,38,39] . Previous studies have demonstrated that LOH at 9p21 correlates with the loss of p16 expression in various types of cancer [22,40] . We also investigated the association between p16 protein expression and LOH at 9p21-22 in gallbladder cancer.…”

Section: Discussionmentioning

confidence: 96%

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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“…Immunohistochemistry was performed according to the indirect biotin-streptavidin-hyperoxidase method, as previously described. 32 The antibody dilutions were 1:75 for oestrogen receptors, 1:100 for maspin, 1:600 for CXCR4, 1:200 for LDH-5 and 1:20 for CD34. Negative controls were created by omitting the primary antibody.…”

Section: Patientsmentioning

confidence: 99%

Simultaneous evaluation of maspin and CXCR4 in patients with breast cancer

Tsoli

Tsantoulis²,

Papalambros³

et al. 2006

J Clin Pathol

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Aim: To study simultaneously the actions of maspin and CXCR4, which share several similar pathways in cancer, including apoptosis and angiogenesis. Methods: Our material consisted of 151 invasive breast carcinomas arranged in a tissue microarray setting. Maspin and CXCR4 expression was evaluated by immunohistochemistry. Microvessel density was assessed by CD34 immunodetection and apoptosis by the Tdt-mediated dUTP nick end labelling assay. Results: Maspin expression was related to CXCR4 expression, apoptosis, patient age and the Nottingham prognostic index. The expression of both maspin and CXCR4 progressively increased in high-grade tumours. In patients with lymph node negative breast cancer, maspin overexpression was associated with increased risk of death. High CXCR4 expression was associated with prolonged survival of patients with high maspin expression. Conclusions: Our results show that maspin overexpression could prove to be a potentially useful marker, especially for the clinically important group of patients with lymph node negative breast cancer. The expression of CXCR4 is of less significance in our study, but may be informative for specific patient subsets or in a longer time frame.

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Expression ofp16INK4A and alterations of the 9p21-23 chromosome region in non-small-cell lung carcinomas: Relationship with tumor growth parameters and ploidy status

Cited by 31 publications

References 24 publications

Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung

Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung

Two distinct pathways of p16 gene inactivation in gallbladder cancer

Simultaneous evaluation of maspin and CXCR4 in patients with breast cancer

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