p16

Our plain-English summary of p16, by S. Serra, R. Chetty (Journal of Clinical Pathology, 2018).

The study

• Authors: S. Serra, R. Chetty
• Journal: Journal of Clinical Pathology
• Published: 2018;71(10):853-858
• Type of article: Review
• Cited by: 110 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The p16 gene belongs to INK4 family of genes and is made up of four members: p16 INK4A , p15 INK4B , p18 INK4C and p19 INK4D , all of which share biological properties, namely, inhibition of cell growth and tumour suppression. After p53, p16 is the second most common tumour suppressor gene. It has been regarded as the familial melanoma gene. Immunohistochemistry for p16 has a well-defined role in distinct pathological scenarios. It is used to distinguish desmoplastic melanoma from reactive fibrous proliferation, with former showing strong nuclear positivity. In other types of melanoma, p16 protein expression is lost. Spitz nevi show retention of nuclear staining for p16. Benign mesothelial proliferations tend to retain nuclear p16 immunoreactivity, while malignant mesotheliomas lose expression. However, p16 fluorescent in-situ hybridisation analysis is recommended in the workup of malignant mesothelioma. Another common application of p16 immunohistochemistry is as an indicator for human papillomavirus (HPV) infection and p16 protein is overexpressed in HPV-associated tumours. In this context, p16 immunopositivity should be strong, diffuse, nuclear or nuclear and cytoplasmic in location. Another use for p16 is demonstration of p16 immunopositivity in well-differentiated and dedifferentiated liposarcoma.

© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This article was a review in the journal's "Gene of the month" series, commissioned and internally peer reviewed. It did not study any patients and did not discuss asbestos or any fiber exposure. The authors described the p16 tumour suppressor gene and its use in diagnosing tumours, including melanoma, fatty tumours, mesothelioma, and lesions linked to human papillomavirus (HPV). On malignant mesothelioma, the authors cited earlier work reporting that about 30% of malignant mesotheliomas show one of three p16 alterations: methylation, deletion or a point mutation. They wrote that almost all benign and reactive mesothelial proliferations keep nuclear p16 staining, while malignant mesotheliomas lose it. They added that failure to show this loss does not exclude malignant mesothelioma. Citing a study by Chiosea and colleagues, they reported that 87% of benign proliferations and 60% of malignant lesions kept p16 staining, including almost 30% of peritoneal mesotheliomas. The authors concluded that p16 fluorescent in-situ hybridisation (FISH) is important in diagnosing malignant mesothelioma. They called it a more reliable way to assess p16 status, and they noted a recommendation to combine it with BAP1 staining.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review (journal 'Gene of the month' series), commissioned and internally peer reviewed
• Who was studied: No patients or samples were studied by the authors; the review covered published work on p16 in many tumour types, including melanoma, fatty tumours, malignant mesothelioma, anogenital and gynaecological lesions, and oropharyngeal squamous carcinoma
• Exposure: Not applicable: the article concerns the p16 gene and p16 laboratory tests (immunohistochemistry and FISH); asbestos and fiber types are not discussed
• Main results:
  • Citing earlier work (Hirao et al.), the authors reported that approximately 30% of malignant mesotheliomas show one of three p16 alterations: methylation, deletion or a point mutation
  • A table adapted from Liggett and Sidransky listed mesothelioma with 50% homozygous deletion and less than 5% mutation of p16
  • The authors wrote that almost all benign and reactive mesothelial proliferations retain nuclear p16 staining on immunohistochemistry, while malignant mesotheliomas show loss of nuclear p16 staining
  • The authors cautioned that failure to show loss of nuclear p16 expression does not exclude a diagnosis of malignant mesothelioma
  • Citing Chiosea and colleagues, the authors reported that benign mesothelial proliferations retained nuclear p16 in 87% of cases, and that 60% of malignant lesions were also positive, including almost 30% of peritoneal mesotheliomas. The authors therefore recommended FISH for p16.
  • Citing Liggett and Sidransky, the authors reported that p16 inactivation occurs in about 26% of all malignancies, second to p53
  • For oropharyngeal squamous carcinoma, the authors reported a recommendation that 70% of tumour cells show strong, diffuse nuclear or nuclear and cytoplasmic p16 staining for the tumour to be labelled HPV-associated
• The authors' conclusion: The authors concluded that p16 FISH analysis is important in diagnosing malignant mesothelioma, and that p16 is the second most common tumour suppressor gene in all cancers, the familial melanoma gene, positive in well-differentiated and dedifferentiated liposarcoma, and a surrogate marker for HPV

Topics

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Desmoplastic Mesothelioma, Malignant Mesothelioma, Well-Differentiated.

Related studies

• CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival — A.M. Krasinskas, D.L. Bartlett, et al. (2010)
• p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer — T. Ito, M. Hamasaki, et al. (2015)
• p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma — H. Hwang, C. Tse, et al. (2014)
• Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma — Q. Hu, S. Akatsuka, et al. (2010)
• Homozygous deletion of CDKN2A in malignant mesothelioma: Diagnostic utility, patient characteristics and survival in a UK mesothelioma centre — K. Marshall, S. Jackson, et al. (2020)
• Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry — T. Hida, M. Hamasaki, et al. (2017)

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