Skip to main content
Top
Published in: Irish Journal of Medical Science (1971 -) 3/2018

Open Access 01-08-2018 | Original Article

p16, p21, and p53 proteins play an important role in development of pancreatic intraepithelial neoplastic

Authors: Justyna Zińczuk, Konrad Zaręba, Katarzyna Guzińska-Ustymowicz, Bogusław Kędra, Andrzej Kemona, Anna Pryczynicz

Published in: Irish Journal of Medical Science (1971 -) | Issue 3/2018

Login to get access

Abstract

Background

Deregulation of cell cycle takes place during the development of many cancers as well as pancreatic ductal adenocarcinoma (PDA), which develops from precursor lesions, most frequently including pancreatic intraepithelial neoplasia (PanIN).

Aims

The aim of this study was to evaluate and compare the expression of p16, p21, and p53 proteins taking part in the regulation of the cell cycle in normal pancreatic ducts and pancreatic intraepithelial neoplasia at its various advancing stages.

Methods

The expressions of p16, p21, and p53 were assessed immunohistochemically in 70 patients with different pancreatic diseases (pancreatic ductal adenocarcinoma, pancreatitis, and pancreatic cysts), showing also pancreatic intraepithelial neoplasia. The results correlated with chosen clinicopathological parameters.

Results

Our study revealed a difference in p16, p21, and p53 expressions between normal pancreatic ducts and various stages of PanIN. p16 expression progressively decreased, whereas p21 and p53 increased from normal pancreas to PanIN 1, 2, and 3. The expression of p21 was associated with age, p53 with PanIN location in the pancreas and p16 with the type of primary diseases. Simultaneously, we observed a directly proportional relationship between the expression of p21 and p53 proteins and inversely proportional between the p16 and the p21 and p53 proteins.

Conclusions

p16, p21, and p53 proteins play an important role in the deregulation of the cell cycle and participate in the development of pancreatic intraepithelial neoplasia. Immunohistochemical evaluation of their expressions may be helpful in the diagnosis of PanIN.
Literature
3.
go back to reference Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP (2008) Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. JOP 9(2):99–132PubMed Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP (2008) Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. JOP 9(2):99–132PubMed
4.
go back to reference Hruban RH, Adsay NV, Albores-Saavedra J et al (2001) Pancreatic intraepithelial neoplasia (PanIN): a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 25(5):579–586CrossRefPubMed Hruban RH, Adsay NV, Albores-Saavedra J et al (2001) Pancreatic intraepithelial neoplasia (PanIN): a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 25(5):579–586CrossRefPubMed
5.
go back to reference Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, Brosens LA, Fukushima N, Goggins M, Hruban RH, Kato Y, Klimstra DS, Klöppel G, Krasinskas A, Longnecker DS, Matthaei H, Offerhaus GJ, Shimizu M, Takaori K, Terris B, Yachida S, Esposito I, Furukawa T, Baltimore Consensus Meeting (2015) A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol 39(12):1730–1741. https://doi.org/10.1097/PAS.0000000000000533 CrossRefPubMedPubMedCentral Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, Brosens LA, Fukushima N, Goggins M, Hruban RH, Kato Y, Klimstra DS, Klöppel G, Krasinskas A, Longnecker DS, Matthaei H, Offerhaus GJ, Shimizu M, Takaori K, Terris B, Yachida S, Esposito I, Furukawa T, Baltimore Consensus Meeting (2015) A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol 39(12):1730–1741. https://​doi.​org/​10.​1097/​PAS.​0000000000000533​ CrossRefPubMedPubMedCentral
6.
go back to reference Abe K, Suda K, Arakawa A et al (2007) Different patterns of p16INK4A and p53 protein expressions in intraductal papillary-mucinous neoplasms and pancreatic intraepithelial neoplasia. Pancreas 34(1):85–91CrossRefPubMed Abe K, Suda K, Arakawa A et al (2007) Different patterns of p16INK4A and p53 protein expressions in intraductal papillary-mucinous neoplasms and pancreatic intraepithelial neoplasia. Pancreas 34(1):85–91CrossRefPubMed
7.
go back to reference Kern SE, Hruban RH, Hollingsworth MA et al (2001) A ‘white paper’: the product of a pancreas cancer think tank. Cancer Res 61(12):4923–4932PubMed Kern SE, Hruban RH, Hollingsworth MA et al (2001) A ‘white paper’: the product of a pancreas cancer think tank. Cancer Res 61(12):4923–4932PubMed
9.
go back to reference Domagała W (2007) Molekularne podstawy karcynogenezy i ścieżki sygnałowe niektórych nowotworów ośrodkowego układu nerwowego. Polski Przegląd Neurologiczny 3(3):127–141 Domagała W (2007) Molekularne podstawy karcynogenezy i ścieżki sygnałowe niektórych nowotworów ośrodkowego układu nerwowego. Polski Przegląd Neurologiczny 3(3):127–141
10.
go back to reference Karamitopoulou E, Zlobec I, Tornillo L, Carafa V, Schaffner T, Brunner T, Borner M, Diamantis I, Zimmermann A, Terracciano L (2010) Differential cell cycle and proliferation marker expression in ductal pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN). Pathology 42(3):229–234. https://doi.org/10.3109/00313021003631379 CrossRefPubMed Karamitopoulou E, Zlobec I, Tornillo L, Carafa V, Schaffner T, Brunner T, Borner M, Diamantis I, Zimmermann A, Terracciano L (2010) Differential cell cycle and proliferation marker expression in ductal pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN). Pathology 42(3):229–234. https://​doi.​org/​10.​3109/​0031302100363137​9 CrossRefPubMed
12.
go back to reference Norfadzilah MY, Pailoor J, Retneswari M et al (2011) P53 expression in invasive pancreatic adenocarcinoma and precursor lesions. Malaysian J Pathol 33(2):89–94 Norfadzilah MY, Pailoor J, Retneswari M et al (2011) P53 expression in invasive pancreatic adenocarcinoma and precursor lesions. Malaysian J Pathol 33(2):89–94
13.
go back to reference Biankin AV, Kench JG, Morey AL, Lee CS, Biankin SA, Head DR, Hugh TB, Henshall SM, Sutherland RL (2001) Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia. Cancer Res 61(24):8830–8837PubMed Biankin AV, Kench JG, Morey AL, Lee CS, Biankin SA, Head DR, Hugh TB, Henshall SM, Sutherland RL (2001) Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia. Cancer Res 61(24):8830–8837PubMed
14.
go back to reference Hermanová M, Lukás Z, Kroupová I et al (2003) Relationship between KRAS mutation and the expression of p21WAF1/CIP1 and p53 in chronic pancreatitis and pancreatic adenocarcinoma. Neoplasma 50(5):319–325PubMed Hermanová M, Lukás Z, Kroupová I et al (2003) Relationship between KRAS mutation and the expression of p21WAF1/CIP1 and p53 in chronic pancreatitis and pancreatic adenocarcinoma. Neoplasma 50(5):319–325PubMed
15.
go back to reference Hermanová M, Lukás Z, Nenutil R et al (2004) Amplification and overexpression of HER-2/neu in invasive ductal carcinomas of the pancreas and pancreatic intraepithelial neoplasms and the relationship to the expression of p21(WAF1/CIP1). Neoplasma 51(2):77–83PubMed Hermanová M, Lukás Z, Nenutil R et al (2004) Amplification and overexpression of HER-2/neu in invasive ductal carcinomas of the pancreas and pancreatic intraepithelial neoplasms and the relationship to the expression of p21(WAF1/CIP1). Neoplasma 51(2):77–83PubMed
16.
go back to reference Qiu W, Sahin F, Iacobuzio-Donahue CA et al (2011) Disruption of p16 and activation of Kras in pancreas increase ductal adenocarcinoma formation and metastasis in vivo. Oncotarget 2(11):862–873CrossRefPubMedPubMedCentral Qiu W, Sahin F, Iacobuzio-Donahue CA et al (2011) Disruption of p16 and activation of Kras in pancreas increase ductal adenocarcinoma formation and metastasis in vivo. Oncotarget 2(11):862–873CrossRefPubMedPubMedCentral
17.
go back to reference Rosty C, Geradts J, Sato N et al (2003) p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatiti. Am J Surg Pathol 27(12):1495–1501CrossRefPubMed Rosty C, Geradts J, Sato N et al (2003) p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatiti. Am J Surg Pathol 27(12):1495–1501CrossRefPubMed
19.
go back to reference Wilentz RE, Geradts J, Maynard R et al (1998) Inactivation of the p16 (INK4A) tumorsuppressor gene in pancreatic duct lesions: loss of intranuclear expression. Cancer Res 58:4740–4744PubMed Wilentz RE, Geradts J, Maynard R et al (1998) Inactivation of the p16 (INK4A) tumorsuppressor gene in pancreatic duct lesions: loss of intranuclear expression. Cancer Res 58:4740–4744PubMed
22.
go back to reference Aguirre AJ, Bardeesy N, Sinha M et al (2003) Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 17:3112–3126CrossRefPubMedPubMedCentral Aguirre AJ, Bardeesy N, Sinha M et al (2003) Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 17:3112–3126CrossRefPubMedPubMedCentral
Metadata
Title
p16, p21, and p53 proteins play an important role in development of pancreatic intraepithelial neoplastic
Authors
Justyna Zińczuk
Konrad Zaręba
Katarzyna Guzińska-Ustymowicz
Bogusław Kędra
Andrzej Kemona
Anna Pryczynicz
Publication date
01-08-2018
Publisher
Springer London
Published in
Irish Journal of Medical Science (1971 -) / Issue 3/2018
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-018-1751-z

Other articles of this Issue 3/2018

Irish Journal of Medical Science (1971 -) 3/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.