C-ERB B2 EXPRESSION IN COLORECTAL CARCINOMA; ITS RELATIONSHIP WITH TUMOR GRADE AND OTHER PROGNOSTIC FACTORS

Abstract

Objective: The multidisciplinary management of colorectal carcinoma (CRC) is based on tumor stage, grade, and presence of vascular invasion. In this approach, information derived from the molecular characteristics of the tumor may be missed. There is a need to determine new prognostic parameters. Human epidermal growth factor 2 (c-erb B2) protein overexpression is implicated in the development of various tumor types, while the data on CRC is ambiguous. This study aimed at determining the frequency of c-erb B2 overexpression in CRC, checking it against prognostic parameters, as it has a special role in breast and gastric cancers. Material and Methods: A total of 71 colectomy specimens diagnosed as CRC at the Mustafa Kemal University Medical Faculty, Department of Pathology between January 2007, and December 2012, were included in this study. The c-erb B2 overexpression of tumor cells was detected by using immunohistochemistry (IHC). Results: Among the 71 CRC cases, 34 (47.9%) of them were c-erb B2 score 0, 22 (31%) of them were score 1, 10 (14.1%) of them were score 2, 5 (7%) of them were score 3. Conclusion: The overexpression of c-erb B2 protein was detected in 21.1% of CRC cases whereas no significant relationship with prognostic parameters was determined

Keywords

• ERBB-2 protein
• colorectal neoplasms
• prognosis

KOLOREKTAL KARSİNOMLARDA C-ERB B2 EKSPRESYONUNUN TÜMÖR DERECESİ VE DİĞER PROGNOSTİK FAKTÖRLERLE İLİŞKİSİ

Abstract

Amaç: Kolorektal karsinomlarda multidisipliner yaklaşımda tümör evresi ve derecesi ile vasküler invazyon varlığı esas alınmaktadır. Bu yaklaşımda tümörün moleküler karakteristik bilgileri atlanabilmektedir. Bu tümörler için yeni prognostik parametrelerin belirlenmesine ihtiyaç duyulmaktadır. Birçok tümör tipinin gelişiminde c-erb B2 proteini aşırı ekspresyonu gösterilmiştir, ancak kolorektal karsinomlarda bu konudaki sonuçlar net değildir. Bu çalışmada meme ve mide kanserinde özel bir rolü olan insan kaynaklı epidermal büyüme faktörü 2 (c-erb B2) proteini aşırı ekspresyonunun kolorektal karsinomlardaki frekansını belirlemek ve prognostik parametrelerle ilişkisini araştırmak hedeflenmiştir. Gereç ve Yöntemler: Ocak 2007 ile Aralık 2012 tarihleri arasında Mustafa Kemal Üniversitesi Tıp Fakültesi Patoloji Bölümü’nde kolorektal karsinom tanısı alan 71 kolektomi örneği bu çalışmaya dahil edilmiştir. Tümör hücrelerinin c-erb B2 protein ekspresyonu, immünohistokimyasal yöntemle araştırılmıştır. Bulgular: Yetmiş bir kolorektal karsinom olgusundan 34 (%47,9) tanesi c-erb B2 skor 0, 22 (%31) tanesi skor 1, 10 (%14,1) tanesi skor 2, 5 (%7) tanesi skor 3olarak değerlendirilmiştir. Sonuç: Kolorektal karsinom olgularının %21,1’inde c-erb B2 proteini aşırı ekspresyonu tespit edilmiştir; ancak prognostik parametrelerle anlamlı bir ilişkisi izlenmemiştir.

Keywords

• ERBB-2 proteini
• kolorektal neoplazmlar
• prognoz

References

1. Boyle P, Langman JS. ABC of colorectal cancer: Epidemiology. BMJ 2000;321(7264):805-8. google scholar
2. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001;2(2):127-37. google scholar
3. Normanno N, Bianco C, Strizzi L, Mancino M, Maiello M R, De Luca A, et al. The ErbB receptors and their ligands in cancer: an overview. Curr Drug Targets 2005;6(3):243-57. google scholar
4. Landgraf R. HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks. Breast Cancer Res 2007;9(1):202. google scholar
5. Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008;52(7):797-805. google scholar
6. Ross JS, McKenna BJ. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest 2001;19(5):554-68. google scholar
7. Zhang XL, Yang YS, Xu DP, Qu JH, Guo MZ, Gong Y, et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg 2009;33(10):2112-8. google scholar
8. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65(1):5-29. google scholar

9. Schuell B, Gruenberger T, Scheithauer W, Zielinski C, Wrba F. HER 2/neu protein expression in colorectal cancer. BMC Cancer 2006;6:123. google scholar
10. Ismail HM, El-Baradie M, Moneer M, Khorshid O, Touny A. Clinico-Pathological and Prognostic Significance of p53, Bcl-2 and Her-2/ neu Protein Markers in Colorectal Cancer Using Tissue Microarray. J Egypt Natl Canc Inst 2007;19(1):3-14. google scholar
11. Kavanagh DO, Chambers G, O’Grady L, Barry KM, Waldron RP, Bennani F, et al. Is overexpression of HER-2 a predictor of prognosis in colorectal cancer? BMC Cancer 2009;9(1):1471-2407. google scholar
12. Jesus EC, Matos D, Artigiani R, Waitzberg AF, Goldenberg A, Saad SS. Assessment of staging, prognosis and mortality of colorectal cancer by tumor markers: receptor erbB-2 and cadherins. Acta Cir Bras 2005;20(6):422-7. google scholar
13. Half E, Broaddus R, Danenberg KD, Danenberg PV, Ayers GD, Sinicrope FA. HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. Int J Cancer 2004;108(4):540-8. google scholar
14. Farzand S, Siddique T, Saba K, Bukhari MH. Frequency of HER2/neu overexpression in adenocarcinoma of the gastrointestinal system. World J Gastroenterol 2014;20(19):5889-96. google scholar
15. Seo AN, Kwak Y, Kim DW, Kang SB, Choe G, Kim WH, Lee HS. HER2 status in colorectal cancer: its clinical significance and the relationship between HER2 gene amplification and expression. PLoS One 2014;9(5):e98528. google scholar
16. Elezoglu B, Tolunay S. The relationship between the stromal mast cell number, microvessel density, c-erbB-2 staining and survival and prognostic factors in colorectal carcinoma. Turk Patoloji Derg 2012;28(2):110-8. google scholar
17. Ljuslinder I, Malmer B, Isaksson-Mettavainio M, Oberg A, Henriksson R, Stenling R, Palmqvist R. ErbB 1-4 expression alterations in primary colorectal cancers and their corresponding metastases. Anticancer Res 2009;29(5):1489-94. google scholar
18. Torabizadeh Z, Nosrati A, Tahvildari S. Human epidermal growth factor receptor expression in colorectal cancer and its relationship with clinicopathological characteristics. Middle East J Dig Dis 2016;8:24-30. google scholar
19. Sayadnejad N, Firouzjahi A, Shafaee S, Golshahi H, Sokouti Z, Gholinia H, et al. Immunohistochemical study of HER2/ neu expression in colorectal cancer and its relation to other clinicopathological criteria and prognostic factors. Int J Cancer Manag 2017;10(5):e5700 google scholar
20. Benli IC, Barut SG. Evaluation of the prevalence of HER-2 expression and its relationship with prognostic parameters in colorectal carcinoma. Istanb Med J 2020;21(3):207-12. google scholar
21. Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis f, Kawakami H, et al. DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol 2021;22:779-89. google scholar