Please ensure Javascript is enabled for purposes of website accessibility
ORIGINAL PAPER
Survivin and caspase-3 and PanIN. Disorders of apoptosis in the process of pancreatic cancer formation
 
More details
Hide details
1
2nd Clinical Department of General, Gastroenterological and Oncological Surgery, Medical University of Bialystok, Bialystok, Poland
 
2
Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland
 
3
Students’ Scientific Association, 2nd Clinical Department of General, Gastroenterological and Oncological Surgery, Medical University of Bialystok, Bialystok, Poland
 
4
Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland
 
 
Submission date: 2022-10-27
 
 
Final revision date: 2023-08-09
 
 
Acceptance date: 2024-02-26
 
 
Publication date: 2024-03-28
 
 
Corresponding author
Konrad Zaręba
2nd Clinical Department of General, Gastroenterological and Oncological Surgery, Medical University of Białystok, M Skłodowskiej- Curie 24a, 15-276 Białystok, Poland
 
 
Medical Studies 2024;40(1):1-7
 
KEYWORDS
TOPICS
ABSTRACT
Introduction::
It is believed that pancreatic intraepithelial neoplasia is an important element of pancreatic carcinogenesis. Apoptosis is the process of programmed cell death. Survivin is one of the proteins that inhibit apoptosis. Caspase-3 is a cysteine protease, and plays important roles in the process of apoptosis.

Aim of the research::
The authors focus on analyzing the expression of survivin and caspase-3 in unchanged tissue and tissue from PanIN lesions. This study may help to better understand the cause-and-effect chain from low-grade intraepithelial neoplasia to high-grade neoplasia and invasive cancer.

Material and methods::
The study used tissue material obtained from 70 patients operated on at the 2nd Department of General, Gastroenterological and Oncological Surgery at the Medical University of Bialystok due to pancreatic diseases: adenocarcinoma (38 patients), chronic pancreatitis (23 patients), pancreatic cysts (9 patients). A total of 239 tissue samples were isolated for clinical examination.

Results::
There were statistically significant differences in survivin expression by sex (p < 0.05) and age (p < 0.05). The level of survivin expression was higher in male patients and patients over 60. There were statistically significant differences between the expression levels of survivin as well as caspase-3 depending on the degree of PanIN [PanIN 1A vs PanIN 1b survivin 15% vs. 38.8% (p < 0.05), and caspase-3 17%; vs. 26.9% (p < 0.05). PanIN 2 vs. PaIN3 survivin 62.4% vs. 85.7% (p < 0.05), caspase-3 36.1% vs. 54.3% (p < 0.05)].

Conclusions::
The expression level of survivin and caspase-3 is inextricably linked with the progression of pancreatic intraepithelial neoplasia. The more advanced neoplasia is, the higher is the expression level.
REFERENCES (25)
1.
Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol 2019; 10: 10-27.
 
2.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
 
3.
Hidalgo M, Cascinu S, Kleeff J, Labianca R, Lohr JM, Neoptolemos J, Real FX, Van Laethem JL, Heinemann V. Addressing the challenges of pancreatic cancer: future directions for improving outcomes. Pancreatology 2015; 15: 8-18.
 
4.
Organization WH. World Cancer Report 2014. Accessed 06 October 2021.
 
5.
United States National Cancer Institute. Pancreatic cancer: statistics 2018, May. Available from: https://www.cancer.net/cancer-.... Accessed 07 October 2018.
 
6.
Bosetti C, Lucenteforte E, Silverman DT, Petersen G, Bracci PM, Ji BT, Negri E, Li D, Risch HA, Olson SH, Gallin- ger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Bamlet WR, Holly EA, Bertuccio P, Gao YT, Hassan M, Yu H, Kurtz RC, Cotterchio M, Su J, Maisonneuve P, Duell EJ, Boffetta P, La Vecchia C. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 2012; 23: 1880-1888.
 
7.
Klein AP, Brune KA, Petersen GM, Goggins M, Tersmet- te AC, Offerhaus GJ, Griffin C, Cameron JL, Yeo CJ, Kern S, Hruban RH. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res 2004; 64: 2634-2638.
 
8.
Murphy SJ, Hart SN, Lima JF, Kipp BR, Klebig M, Win- ters JL, Szabo C, Zhang L, Eckloff BW, Petersen GM, Scherer SE, Gibbs RA, McWilliams RR, Vasmatzis G, Couch FJ. Genetic alterations associated with progression from pancreatic intraepithelial neoplasia to invasive pancreatic tumor. Gastroenterology 2013; 145: 1098-1109.
 
9.
Zińczuk J, Zaręba K, Guzińska-Ustymowicz K, Kędra B, Kemona A, Pryczynicz A. Expression of chosen cell cycle and proliferation markers in pancreatic intraepithelial neoplasia. Gastroenterology Rev 2018; 13: 118-126.
 
10.
Misiura M, Zińczuk J, Zaręba K, Kamińska D, Guzińska-Ustymowicz K, Pryczynicz A. Actin-bundling proteins (actinin-4 and fascin-1) are involved in the development of pancreatic intraepithelial neoplasia (PanIN). Am J Med Sci 2020; 359: 147-155.
 
11.
Brosens LA, Hackeng WM, Offerhaus GJ, Hruban RH, Wood LD. Pancreatic adenocarcinoma pathology: changing landscape. J Gastrointest Oncol 2015; 6: 358-374.
 
12.
Distler M, Aust D, Weitz J, Pilarsky C, Grützmann R. Precursor lesions for sporadic pancreatic cancer: PanIN, IPMN, and MCN. Biomed Res Int 2014; 2014: 474905.
 
13.
Kim GE, Bae HI, Park HU, Kuan SF, Crawley SC, Ho JJ, Kim YS. Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. Gastroenterology 2002; 123: 1052-1060.
 
14.
Biankin AV, Kench JG, Biankin SA, Lee CS, Morey AL, Dijkman FP, Coleman MJ, Sutherland RL, Henshall SM. Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrence. Am J Surg Pathol 2004; 28: 1184-1192.
 
15.
Westphal S, Kalthoff H. Apoptosis: targets in pancreatic cancer. Mol Cancer 2003; 2: 6.
 
16.
Wang Q, Zhang L, Yuan X, Ou Y, Zhu X, Cheng Z, Zhang P, Wu X, Meng Y, Zhang L. The relationship between the Bcl-2/Bax proteins and the mitochondria-mediated apoptosis pathway in the differentiation of adipose-derived stromal cells into neurons. PLoS One 2016; 11: e0163327.
 
17.
Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997; 3: 917-921.
 
18.
Vranic A. Caspase-3 and survivin expression in primary atypical and malignant meningiomas. ISRN Neurosci 2013; 19: 26290.
 
19.
Konstantinidou AE, Givalos N, Gakiopoulou H, Korkolopoulou P, Kotsiakis X, Boviatsis E, Agrogiannis G, Mahera H, Patsouris E. Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas. Apoptosis 2007; 12: 695-705.
 
20.
Chakravarti A, Zhai GG, Zhang M, Malhotra R, Lat- ham DE, Delaney MA, Robe P, Nestler U, Song Q, Loef- fler J. Survivin enhances radiation resistance in primary human glioblastoma cells via caspase-independent mechanisms. Oncogene 2004; 23: 7494-7506.
 
21.
Zhang M, Zhang X, Zhao S, Wang Y, Di W, Zhao G, Yang M, Zhang Q. Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients. Target Oncol 2014; 9: 349-357.
 
22.
Liu BB, Wang WH. Survivin and pancreatic cancer. World J Clin Oncol 2011; 2: 164-168.
 
23.
Kami K, Doi R, Koizumi M, Toyoda E, Mori T, Ito D, Fujimoto K, Wada M, Miyatake S, Imamura M. Survivin expression is a prognostic marker in pancreatic cancer patients. Surgery 2004; 136: 443-448.
 
24.
Bhanot U, Heydrich R, Möller P, Hasel C. Survivin expression in pancreatic intraepithelial neoplasia (PanIN): steady increase along the developmental stages of pancreatic ductal adenocarcinoma. Am J Surg Pathol 2006; 30: 754-759.
 
25.
Hurtado M, Sankpal UT, Kaba A, Mahammad S, Chhabra J, Brown DT, Gurung RK, Holder AA, Vishwanatha JK, Basha R. Novel survivin inhibitor for suppressing pancreatic cancer cells growth via downregulating Sp1 and Sp3 transcription factors. Cell Physiol Biochem 2018; 51: 1894-1907.
 
eISSN:2300-6722
ISSN:1899-1874
Journals System - logo
Scroll to top