<i>p16</i>

Serra, Stefano; Chetty, Runjan

doi:10.1136/jclinpath-2018-205216

Cited by 96 publications

(79 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The CDKN2A gene is a tumor suppressor gene located on chromosome 9 band 21.3; it encodes for several transcript variants, which differ in their first exons, and two major proteins: P16INK4a, which is a cyclin-dependent kinase inhibitor, and p14ARF, which binds the p53-stabilizing protein MDM2 ( 11 ). P16INK4a, through the inhibition of CDK4 and CDK6 (cyclin-dependent kinases 4 and 6), activates the retinoblastoma protein (RB), which blocks cellular cycle progression from phase G1 to phase S ( 12 ). CDKN2A mutations are commonly found in familial melanoma ( 13 ), and it has been hypothesized that alterations in cell cycle control genes are necessary for the acquisition of invasive potential and the transformation into invasive melanoma ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

“…CDKN2A mutations determine the alteration of protein P16INK4a expression. Many authors have demonstrated that P16INK4a immunohistochemical expression is preserved in benign nevi and is lost in CM ( 14 ), except for desmoplastic melanoma ( 12 ). While P16INK4a has been shown to be of little use when used alone; a panel encompassing P16INK4a, Ki67, and HMB45 is more effective in the differential diagnosis of melanocytic lesions in clinical practice ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of P16INK4a in Uveal Melanoma: New Perspectives

et al. 2020

View full text Add to dashboard Cite

Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite sharing the name and similar morphological features with cutaneous melanoma (CM), it is an entirely different neoplasia with a particular genetic background and clinical behavior. CDKN2A is a gene located at chromosome 9p21, encoding for P16INK4a and P14(ARF) proteins, whose role as a tumor suppressor has been clearly defined in many malignant tumors. CDKN2A frequently presents germline mutations in familial CM and epigenetic downregulation in a considerable percentage of sporadic CM. It has been hypothesized that CDKN2A alterations are early events in CM development, playing a central role in the malignant transformation of melanocytes. Alterations of the CDKN2A gene reduce the expression of P16INK4a in most CM subtypes. Immunohistochemical evaluation of P16INK4a is currently used, in association with Ki67 and HMB45, in pathology practice to discriminate between dysplastic nevi and melanoma. On the other hand, CKDN2A is rarely mutated in UM, and the immunohistochemical expression of P16INK4a has only been reported in small case series. We tested P16INK4a expression on paraffin-embedded tissue sections from 9 tissue microarrays (TMAs), built with 2 mm cores derived from 133 uveal melanoma FFPE blocks, collected from 1990 to 2018, and from selected paraffin-blocks of 3 UM liver metastases. The immunohistochemical expression of P16INK4a was assessed with a visual evaluation by light microscopy and then with a digital approach. Both approaches, with an acceptable concordance rate, revealed P16INK4a expression in a large proportion of UM cases and all liver metastases, opening new possibilities of using it in the differential diagnosis between cutaneous and uveal melanoma metastases in cases of unknown primary tumor or patients with two different primary melanomas.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of P16INK4a in Uveal Melanoma: New Perspectives

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, p16 mutations appear to be infrequent in prostate cancer (4); moreover, p16 overexpression in cancer has not yet been fully clarified. Certain types of tumour, such as melanoma, HPV-associated tumours, non-small cell lung cancer, mesothelioma and lymphoma exhibit diminished p16 protein levels (5)(6)(7), while in other tumours, including prostate cancer, the overexpression of wild-type or mutant p16 has been found (8,9). p16 overexpression is associated with tumour recurrence (10), and with a poor clinical course in patients with erythroblast transformation-specific-related gene (ERG)-negative prostate cancer (11); therefore, although p16 acts as a tumour suppressor gene, stress or oncogenic factors or alternative molecular events may overcome the role of p16 as a negative cell cycle regulator (12).…”

Section: Introductionmentioning

confidence: 99%

p16 and its putative interplay with metabolic factors in prostate cancer: An analysis based on public TCGA data

et al. 2020

View full text Add to dashboard Cite

p16 is one of the most common tumour suppressor genes, mainly due to its genetic inactivation. However, the clinical significance of p16 in prostate cancer is not yet fully understood, and although p16 acts as a tumour suppressor gene, stress or oncogenic factors or alternative molecular events may overcome the role of p16 as a negative cell cycle regulator. p16 seems to be involved in the metabolic switch to glycolysis during tumorigenesis, possibly interacting with NADPH oxidase 4 (NOX4) and pyruvate kinase type M2 (PKM2), involved in energy metabolism, with differences depending on cell type. The aim of this study was to assess the putative crosstalk between p16, NOX4 and PKM2, with an involvement of miRNA-mediated regulation, in prostate cancer. Transcriptome data from a cohort of 243 patients were extracted from The Cancer Genome Atlas (TCGA) database. An elevated p16 expression level was significantly associated a high Gleason score, decreasing with the score (P<0.0001). NOX4 and PKM2 expression exhibited a similar trend as p16, with higher values in the samples with Gleason scores of 9-10 samples (P<0.0001 and P=0.02, respectively). Moreover, bioinformatics analysis by TargetScan revealed that miR-625-5p could bind to the 3'UTR of p16. A consequential pairing of the NOX4 and PKM2 target region with miR-23a-3p and miR-122-5p, respectively was also found. Of note, the miR-625-5p levels inversely correlated with p16 expression, miR-23a-3p and miR-122 with NOX4 and PKM2, respectively (data not shown). Taken together, these data suggest an interplay between p16 and metabolic factors, such as NOX4 and PKM2, and a miRNA regulation, with a potential clinical impact for the development of novel therapeutic strategies in prostate tumours.

show abstract

“…Due to the location of the tumor (vulva), we wondered if this expression was related to the presence of HPV infection. We didn't find HPV infection, but we know that p16 is not only associated with HPV infection but it's also a tumor suppressor gene implicated in several tumors [28].…”

Section: Resultsmentioning

confidence: 99%

Low grade malignant eccrine spiradenoma of the vulva: case report, review of the literature and discussion about the role of p53 and HPV

2020

View full text Add to dashboard Cite

Background: Malignant eccrine spiradenoma is one of the rarest sweat-gland tumors. Here, we describe a rare case of low grade malignant eccrine spiradenoma located at the vulva. Case presentation: The vulvar lesion was described as a mass measured 3.5 cm and located in the dermis and subcutis with no attachment to the epidermis. The neoplasm was arranged in ragged sheets or solid nodules sometimes with focal necrosis. The tumor cells had hyperchromatism, pleomorphism, and prominent nucleoli with high mitotic index and KI-67 estimated at 70-80%. Conclusions: It's only the fifth case of malignant eccrine spiradenoma localized at the vulva. This is the first time that an HPV genotyping was made in this type of lesion with no HPV found while the p16 expression was diffuse. Moreover, it's the first time that a p53 mutation is detected by sequencing in this location.

show abstract

p16

Abstract: The p16 gene belongs to INK4 family of genes and is made up of four members: p16INK4A, p15INK4B, p18INK4C and p19INK4D, all of which share biological properties, namely, inhibition of cell growth and tumour suppression. After p53, Show more

Cited by 96 publications

References 24 publications

Expression of P16INK4a in Uveal Melanoma: New Perspectives

Expression of P16INK4a in Uveal Melanoma: New Perspectives

p16 and its putative interplay with metabolic factors in prostate cancer: An analysis based on public TCGA data

Low grade malignant eccrine spiradenoma of the vulva: case report, review of the literature and discussion about the role of p53 and HPV

Contact Info

Product

Resources

About