1. bookAHEAD OF PRINT
Journal Details
License
Format
Journal
eISSN
2501-062X
First Published
30 Mar 2015
Publication timeframe
4 times per year
Languages
English
access type Open Access

Epidermal Growth Factor Receptor immunohistochemical expression in hepatocellular carcinoma without Epidermal Growth Factor Receptor exons 18–21 mutations

Published Online: 27 Apr 2022
Volume & Issue: AHEAD OF PRINT
Page range: -
Received: 26 Feb 2022
Journal Details
License
Format
Journal
eISSN
2501-062X
First Published
30 Mar 2015
Publication timeframe
4 times per year
Languages
English
Abstract

Introduction: EGFR targeted therapies, have been proved beneficial for patients with HCC, nevertheless additional research on EGFR immunoexpresion and EGFR mutations is still needed, especially in population in which it has not been done yet. The aim of this study is to evaluate EGFR immunoexpression in HCC without EGFR exons 18-21 mutations and to evaluate its influence on survival in HCC patients in North Macedonia.

Methods: We studied 31 cases of HCC for EGFR immunohistochemical expression and EGFR exons 18–21 mutations. The following clinical parameters were analyzed: Hepatitis B and C virus infection, presence of cirrhosis, tumor size, enlarged lymph nodes, metastases, alpha fetoprotein level and overall survival. Presence of the EGFR immunosignal (membranous and cytoplasmic) and the percentage of positive tumor cells in the entire tumor tissue specimen were semi-quantitatively determined.

Results: Hepatitis B and C virus infection, tumor size, metastatic disease and EGFR immunoexpression have influence on patient’s survival. No EGFR exons 18–21 mutations were detected in this group of HCCs. EGFR expression of 61%-80% in tumor tissue significantly influenced survival of the patients (p < 0.01). Multiple Cox regression confirmed tumor size of 5-10cm (p < 0.05), tumor size > 10 cm (p < 0.01) and EGFR expression in range of 61% to 80% (p < 0.05) as independent survival predictors in patients with HCC.

Conclusion: EGFR overexpression in range of 61% to 80% was an independent survival predictor in patients with HCC, implying that these patients could benefit from EGFR inhibition. However, the absence of EGFR mutations in exons 18-21 in any of the cases of this study suggest that single drug EGFR targeted therapy in patients with HCC may be insufficient.

Keywords

1. GALUN D, BASARICc D, ZUVEALA M, BULAJIC P, BOGDANOVIC A, BIDZIC N, et al. Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols. World J Hepatol 2015 Sep 18;7(20):2274–2291.10.4254/wjh.v7.i20.2274 Search in Google Scholar

2. EL-SERAG HB. Hepatocellular carcinoma. N Engl J Med 2011;365:1118-1127.10.1056/NEJMra1001683 Search in Google Scholar

3. WRZESINSKI SH, TADDEI TH, STRAZZABOSCO M. Systemic Therapy in Hepatocellular Carcinoma. Clin Liver Dis. 2011 May;15(2):423–41.10.1016/j.cld.2011.03.002 Search in Google Scholar

4. SUEANGOEN N, TANTIWETRUEANGDET A, PANVICHIAN R. HCC-derived EGFR mutants are functioning, EGF-dependent, and erlotinib-resistant. Cell Biosci 2020 Mar;16:10:41.10.1186/s13578-020-00407-1 Search in Google Scholar

5. BRUIX J, SHETMAN M. American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: An update. Hepatology 2011;53:1020-1022.10.1002/hep.24199 Search in Google Scholar

6. WORNS MA, GALLE PR. Future perspectives in hepatocellular carcinoma. Dig Liver Dis 2010 Jul;42 Suppl 3:S302-9.10.1016/S1590-8658(10)60521-X Search in Google Scholar

7. WHITTAKER S, MARAIS R, ZHU AX. The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010 Sep;29(36):4989–5005.10.1038/onc.2010.23620639898 Search in Google Scholar

8. SESHACHARYULU P, PONNUSAMY MP, HARIDAS D, JAIN M, GANTI AK, BATRA SK. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 2012;16(1):15-31.10.1517/14728222.2011.648617329178722239438 Search in Google Scholar

9. KOMPOSCH K, SIBILIA M. EGFR Signaling in Liver Diseases. Int J Mol Sci 2016 Jan;17(1):30.10.3390/ijms17010030473027626729094 Search in Google Scholar

10. DIMIRI M, SATYANARAYANA A. Molecular Signaling Pathways and Therapeutic Targets in Hepatocellular Carcinoma. Cancers 2020;12(2):491.10.3390/cancers12020491707251332093152 Search in Google Scholar

11. SU MC, LIEN HC, JENG YM. Absence of epidermal growth factor receptor exon 18-21 mutation in hepatocellular carcinoma. Cancer Lett 2005 Jun 16;224(1):117-121.10.1016/j.canlet.2004.10.01015911107 Search in Google Scholar

12. NIKOLOVA D, CHALOVSKA IVANOVA V, GENADIEVA DIMITROVA M, NIKOLOVSKA E, VOLKANOVSKA A, OROVCHANEC N, et al. Immunohistochemical expression of Epidermal Growth Factor Receptor in Hepatocellular Carcinoma. Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2018 Dec 1;39(2-3):21-28.10.2478/prilozi-2018-003830864368 Search in Google Scholar

13. NIKOLOVA D, CHALOVSKA IVANOVA V, GENADIEVA DIMITROVA M, JOVANOVIK R, KOSTADINOVA KUNOVSKA S, OROVCHANEC N, et al. Hepatocellular carcinoma - clinicopathological characteristics, survival, and expression of various histologic molecular markers. Pol J Pathol 2019;70(4):269-276.10.5114/pjp.2019.9312932146796 Search in Google Scholar

14. PORTOLANI N, CONIGLIO A, GHIDONI S, GIOVANELLI M, BENETTI A, TIBERIO GAM, et al. Early and Late Recurrence After Liver Resection for Hepatocellular Carcinoma. Prognostic and Therapeutic Implications. Ann Surg 2006 Feb;243(2):229–235.10.1097/01.sla.0000197706.21803.a1144891916432356 Search in Google Scholar

15. HEIMBACH JK, KULIK LM, FINN RS, SIRLIN CB, ABECASSIS MM, ROBERTS LR, et al. AASLD Guidelines for the Treatment of Hepatocellular Carcinoma. Hepatology 2018;67(1):358-380.10.1002/hep.2908628130846 Search in Google Scholar

16. BELGHITI J, KIANMANESH R. Surgical treatment of hepatocellular carcinoma. HPB 2005; 7(1):42–49.10.1080/13651820410024067202392118333160 Search in Google Scholar

17. YEH CN, LEE WC, CHEN MF. Hepatic resection and prognosis for patients with hepatocellular carcinoma larger than 10 cm: two decades of experience at Chang Gung memorial hospital. Ann Surg Oncol 2003;10:1070–6.10.1245/ASO.2003.03.07214597446 Search in Google Scholar

18. BERASAIN C, AVILA MA. The EGFR signalling system in the liver: from hepatoprotection to hepatocarcinogenesis. J Gastroenterol 2014 Jan:49 (1):9–23.10.1007/s00535-013-0907-x24318021 Search in Google Scholar

19. BERASAIN C, PERUGORRIA MJ, LATESA MU, CASTILLO J, GONI S, SANTAMARIA M, et al. The epidermal growth factor receptor: a link between inflammation and liver cancer. Exp Biol Med (Maywood). 2009;234:713–25.10.3181/0901-MR-1219429859 Search in Google Scholar

20. LEE JS. The mutational landscape of hepatocellular carcinoma. Clin Mol Hepatol 2015 Sep; 21(3):220–229..10.3350/cmh.2015.21.3.220461228226523267 Search in Google Scholar

21. ZHU AX, ROSMODRUC O, EVANS JTR, ROSS PJ, SANTORO A, CARRILHO FJ, et al. SEARCH: A Phase III, Randomized, Double-Blind,Placebo-Controlled Trial of Sorafenib Plus Erlotinib in Patients With Advanced Hepatocellular Carcinoma. J Clin Oncol 2015 Feb 20;33:559-566.10.1200/JCO.2013.53.774625547503 Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo