Overexpression of p53 in extra large (more than 10 cm) hepatocellular carcinoma
Background: Extra large hepatocellular carcinoma (HCC) of >10 cm managed in our center shows a specific characteristic in tropical regions. This type of HCC exhibits distinct p53 expression. This study aimed to determine the association between p53 expression and tumor size and behavior.
Method: Subjects with HCC who underwent surgical resection in our hospital during 2012–2015 were enrolled in this
study. Subject’s characteristics, tumor size, histopathology findings, and tumor behavior were variables observed. An
immunohistochemical study on p53 expression was conducted to determine its association with those variables.
Results: This study involved 38 subjects with tumor size ranging from 3 cm to 25 cm in diameter and 20 subjects (52.8%) with tumor size ranging from 10 cm to 25 cm in diameter. Only 13 samples were evaluated for p53 expression. Five subjects with >10 cm (extra large) tumor showed highly/overexpressed p53 (intensity>50%), two subjects with strong p53 expression (intensity>5%–50%), and two subjects with weak expression. Three subjects with <10 cm (large) tumor showed strong expression of p53 (5%–9%) and a subject with 3 cm tumor showed weak p53 expression (<5%). Highly expressed p53 was found in patients with microvascular invasion, inflammatory response, mitosis, and necrosis.
Conclusion: Overexpression of p53 was associated with extra large and poorly differentiated HCC.
Ruiz I, Féray C. Current management of hepatocellular carcinoma. Cancer Radiother. 2015;19(6–7):410–5. https://doi.org/10.1016/j.canrad.2015.05.008
Han JH, Kim DG, Na GH, Kim EY, Lee SH, Hong TH, et al. Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma. World J Gastroenterol. 2014;20(45):17132–40. https://doi.org/10.3748/wjg.v20.i45.17132
Truant S, Boleslawski E, Duhamel A, Bouras AF, Louvet A, Febvay C, et al. Tumor size of hepatocellular carcinoma in noncirrhotic liver: a controversial predictive factor for outcome after resection. Eur J Surg Oncol. 2012;38(12):1189–96. https://doi.org/10.1016/j.ejso.2012.07.112
Choo SP, Tan WL, Goh BK, Tai WM, Zhu AX. Comparison of hepatocellular carcinoma in Eastern versus Western populations. Cancer. 2016;122(22):3430–46. https://doi.org/10.1002/cncr.30237
Fabregat I. Dysregulation of apoptosis in hepatocellular carcinoma cells. World J Gastroenterol. 2009;15(5):513–20. https://doi.org/10.3748/wjg.15.513
Marquardt JU, Galle PR, Teufel A. Molecular diagnosis and therapy of hepatocellular carcinoma (HCC): an emerging field for advanced technologies. J Hepatol. 2012;56(1):267–75. https://doi.org/10.1016/j.jhep.2011.07.007
Zhou T, Ye L, Bai Y, Sun A, Cox B, Liu D, et al. Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog. PLoS One. 2014;9(9):e107876. https://doi.org/10.1371/journal.pone.0107876
Zilfou JT, Lowe SW. Tumor suppressive functions of p53. Cold Spring Harb Perspect Biol. 2009;1(5):a001883. https://doi.org/10.1101/cshperspect.a001883
Kunst C, Haderer M, Heckel S, Schlosser S, Müller M. The p53 family in hepatocellular carcinoma. Transl Cancer Res. 2016;5(6):632–8. https://doi.org/10.21037/tcr.2016.11.79
Muller PAJ, Vousden KH. Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell. 2014;25(3):304–17. https://doi.org/10.1016/j.ccr.2014.01.021
Sanyal AJ, Yoon SK, Lencioni R. The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist. 2010;15(Supplement 4):14–22. https://doi.org/10.1634/theoncologist.2010-S4-14
Liu J, Li W, Deng M, Liu D, Ma Q, Feng X. Immunohistochemical determination of p53 protein overexpression for predicting p53 gene mutations in hepatocellular carcinoma: a meta-analysis. PLoS One. 2016;11(7):e0159636. https://doi.org/10.1371/journal.pone.0159636
Yang XD, Pan LH, Wang L, Ke Y, Cao J, Yang C, et al. Systematic review of single large and/or multinodular hepatocellular carcinoma: surgical resection improves survival. Asian Pac J Cancer Prev. 2015;16(13):5541–7. https://doi.org/10.7314/APJCP.2015.16.13.5541
Zhong JH, Rodríguez AC, Ke Y, Wang YY, Wang L, Li LQ. Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion. Medicine. 2015;94(3):e396. https://doi.org/10.1097/MD.0000000000000396
Zhan P, Ji YN. Prognostic significance of TP53 expression for patients with hepatocellular carcinoma: a meta-analysis. Hepatobiliary Surg Nutr. 2014;3(1):11–7.
Qin LX, Tang ZY, Ma ZC, Wu ZQ, Zhou XD, Ye QH, et al. P53 immunohistochemical scoring: an independent prognostic marker for patients after hepatocellular carcinoma resection. World J Gastroenterol. 2002;8(3):459–63. https://doi.org/10.3748/wjg.v8.i3.459
Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene. 2003;22(56):9030–40. https://doi.org/10.1038/sj.onc.1207116
Charni M, Aloni-Grinstein R, Molchadsky A, Rotter V. P53 on the crossroad between regeneration and cancer. Cell Death Differ. 2017;24(1):8–14. https://doi.org/10.1038/cdd.2016.117
Jiang P, Du W, Heese K, Wu M. The Bad guy cooperates with good cop p53: Bad is transcriptionally up-regulated by p53 and forms a Bad/p53 complex at the mitochondria to induce apoptosis. Mol Cell Biol. 2006;26(23):9071–82. https://doi.org/10.1128/MCB.01025-06
Guan YS, He Q, La Z. Roles of p53 in carcinogenesis, diagnosis and treatment of hepatocellular carcinoma. J Cancer Mol. 2006;2(5):191–7.
Aravalli RN, Cressman EN, Steer CJ. Cellular and molecular mechanisms of hepatocellular carcinoma: an update. Arch Toxicol. 2013;87(2):227–47. https://doi.org/10.1007/s00204-012-0931-2
Graur F, Furcea L, Mois E, Biliuta A, Rozs AT, Negrean V, et al. Analysis of p53 protein expression in hepatocellular carcinoma. J Gastrointestin Liver Dis. 2016;25(3):345–9.
Pedica F, Ruzzenente A, Bagante F, Capelli P, Cataldo I, Pedron S, et al. A re-emerging marker for prognosis in hepatocellular carcinoma: the add-value of FISHing c-myc gene for early relapse. PLoS One. 2013;8(7):e68203. https://doi.org/10.1371/journal.pone.0068203
Cioca A, Cimpean AM, Kundnani NR, Ceausu R, Suciu C, Raica M. P53 expression as a prognostic marker in hepatocellular carcinoma. Arch Biol Sci. 2014;66(2):841–5. https://doi.org/10.2298/ABS1402841C
Yang SF, Chang CW, Wei RJ, Shiue YL, Wang SN, Yeh YT. Involvement of DNA damage response pathways in hepatocellular carcinoma. Biomed Res Int. 2014;2014:153867. https://doi.org/10.1155/2014/153867
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