ArticleJournal of cancer research and clinical oncology2003
p16INK4A alterations are accompanied by aberrant protein immunostaining in endometrial carcinomas.
Article in Journal of cancer research and clinical oncology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Clinicopathological Significance and Potential Drug Target of CDKN2A/p16 in Endometrial Carcinoma.Scientific reports · 2015Pooled it
- Aberrant promoter hypermethylation of p16 gene in endometrial carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Pooled it
- Research Progress of DNA Methylation in Endometrial Cancer.Biomolecules · 2022Review
- PRMT5 promotes progression of endometrioid adenocarcinoma via ERα and cell cycle signaling pathways.The journal of pathology. Clinical research · 2021Article
- Over-expression of HDAC8 down-regulate CDKN2A is associated with worse prognosis of esophageal squamous cell carcinoma.Translational cancer research · 2020Article
- Recent findings on epigenetic gene abnormalities involved in uterine cancer.Molecular and clinical oncology · 2017Article
- Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers.Frontiers in oncology · 2015Article
- hMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases.Clinical & experimental metastasis · 2012Article
- The genomics and genetics of endometrial cancer.Advances in genomics and genetics · 2012Article
- DNA methylation in endometrial cancer.Epigenetics · 2010Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo date, the significance of p16INK4A tumor suppressor gene inactivation in sporadic endometrial cancer (EC) has only rarely been described. In this study, we examined the alteration type and frequency of gene alterations [point mutations, aberrant promoter methylation and loss of heterozygosity (LOH)] in 50 sporadic ECs, and correlated the genetic findings with the immunohistochemical expression of the p16INK4A protein and the classical clinicopathological features.
methodsGene mutations were detected by PCR-SSCP-sequencing analysis, promoter hypermethylation by methylation-specific PCR (MSP), and LOH by PCR of the STS-marker c5.1.
resultsIn total, p16INK4A alterations were found in 14 of 50 (28%) sporadic ECs. In six (12%) cases, two alterations occurred simultaneously. Partial p16INK4A deletions were found in four of 50 (8%) samples. There was one missense mutation (codon 70; CCC-->GCC) and one frameshift mutation (1-bp deletion in exon 2). Only 2 of 47 (4.2%) tumors exhibited aberrant promoter methylation. An allelic loss was detected in 12 of 50 (24%) carcinomas with a higher incidence in advanced endometrial carcinomas than in early-stage uterine tumors. p16INK4A alterations were generally accompanied by gene silencing, confirmed by aberrant protein immunostaining ( r=-0.442; P=0.001). There was a significant difference in the frequency of p16INK4A alterations between early (stage I; 18%) and advanced (stages II-IV; 58%) ECs ( P=0.022). One case showed complete protein loss, but absence of genetic alterations.
conclusionsOur data indicate that p16INK4A inactivation plays a role in the tumorigenesis of the subset of sporadic ECs, particularly in cases exhibiting an aggressive clinical behavior. We demonstrate that p16INK4A methylation can act efficiently and similarly to other genetic alterations as one of the two necessary hits according to the Knudson two-hit hypothesis of tumor suppressor gene inactivation.
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