The Expression of HER-2 and Ki-67 in Oesophageal Neoplasms

Title: The Expression of HER-2 and Ki-67 in Oesophageal Neoplasms

Authors: Meenakshi Somasundaram, Revathi Ramakrishnan

DOI: https://dx.doi.org/10.18535/jmscr/v5i6.117

Abstract

Introduction: HER 2 is amplified in up to 25% of patients with oesophageal carcinomas. The presence of this amplification provides a valuable novel therapeutic target for this group of patients. In patients with breast cancer who are HER 2 positive, trastuzumab, [a fully humanized monoclonal antibody which directed at HER 2 which binds the external domain of the receptor and exerts its action]reduced recurrence by about 50 percent. So, esophageal cancer recurrence rate is also expected to reduce with this treatment. None of the ligand belonging to the epidermal growth factor family activates HER 2.

Expression of Ki67 is also an independent prognostic factor.Ki67 are found only in actively proliferating cells. Tumors with deeper invasion and an advance stage showed an overexpression of Ki-67 than those tumors that had a superficial invasion and an early stage. Both HER2 and Ki67 expression is done in this study. This study is to evaluate the expression of HER-2 and KI-67 in oesophageal neoplasms and to analyze the value of expression of HER-2 and Ki-67 in determining the prognosis.

Materials and Methods: This is a prospective study undertaken during the period from August 2013 to August 2015. Both the surgical specimens and biopsy material were processed and histopathological diagnosis was made

All the resected specimens were fixed in 10% formalin for 24-48 hours. The immunohistochemical detection of biochemical markers was conducted using monoclonal primary antibody (anti-HER and MIB 1) against HER 2 cytoplasmic antigen and KI-67 nuclear antigen respectively. The super sensitive TM polymer-HRP detection system using biotin polymeric technology was used. In this technique, secondary antibody conjugated to poly-HRP reagent and bound to the primary antibody, is visualized by the DAB. HER 2 and KI67 expressions were interpreted as 0, 1+, 2+ ,3+ ,4+.

Observation and Results: This study is a retrospective one which includes 150 oesophageal biopsies and specimens sent from the medical, surgical and surgical gastroenterology departments , during the period of August 2013 to August 2015.

Out of the 150 samples, 113 were biopsies and 37 were surgical specimens. Of that10 were negative for malignancy on histopathological examination. The rest of 140 samples were taken for study.In total number of cases of squamous cell carcinomas, 12.5% of the cases are positive for HER2, 25% show equivocal results with HER2 and 62.5% of the cases are negative for HER2In total number of cases of esophageal adenocarcinoma, 38.46% of cases are positive for HER 2, 30.76% of cases are equivocal, 30.76% of cases are negative for HER 2 .

In our study, squamous cell carcinomas (Grade 1-16.66%, Grade 2-66.66%, Grade3-16.66%%) cases with >30% Ki67 expression was seen in 33.33% of cases and they were Grade 2 tumors. In adenocarcinoma (Grade3-75%, Grade 2-25%%), >30% Ki67expression was seen in % of cases and they were grade 3 tumors.

Conclussion: Ki 67 expression proves to be an independent prognostic factor. There is no correlation between the expression of HER2 and Ki 67 expression

Key Words: HER2, Ki 67, oesophageal carcinomas.

References

1. Akamatsu M, Matsumoto T, Oka K, Yamasaki S, Sonoue H, Kajiyama Y, et al. c-erbB-2 oncoprotein expression related to chemoradioresistance in esophageal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2003;57(5):1323–1327. doi: 10.1016/S0360-3016(03)00782]

2. Anderson KS, LaBaer J. The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res. 2005;4:1123–1133. doi: 10.1021/pr0500814.

3. Bagaria B, Sood S, Sharma R, Lalwani S. Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis) Cancer Biol Med. 2013;10(3):148–157.

4. Berry MF. Esophageal cancer: staging system and guidelines for staging and treatment. J Thorac Dis. 2014;6(3):289.

5. Bird-Lieberman EL, Dunn JM, Coleman HG, Lao-Sirieix P, Oukrif D, Moore CE, et al. Population-based study reveals new risk-stratification biomarker panel for Barrett’s esophagus. Gastroenter-ology. 2012;143(4):927–935 e3. doi: 10.1053/j.gastro.2012.06.041.

6. Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA, Eloubeidi MA. The accuracy of endoscopic ultrasonography with fine-needle aspiration, integrated positron emission tomography with computed tomography, and computed tomography in restaging patients with esophageal cancer after neoadjuvant chemoradiotherapy. J Thorac Cardiovasc Surg. 2005;129:1232–1241. doi: 10.1016/j.jtcvs.2004.12.042

7. Chan DS, Twine CP, Lewis WG. Systematic review and meta-analysis of the influence of HER2 expression and amplification in operable oesophageal cancer. J Gastrointest Surg. 2012;16(10):1821–1829. doi: 10.1007/s11605-012-1979-2.

8. DiMaio MA, Kwok S, Montgomery KD, Lowe AW, Pai RK. Immunohistochemical panel for distinguishing esophageal adenocarcinoma from squamous cell carcinoma: a combination of p63, cytokeratin 5/6, MUC5AC, and anterior gradient homolog 2 allows optimal subtyping. Hum Pathol. 2012;43(11):1799–1807. doi: 10.1016/j.humpath.2012.03.019.

9. Dong J, Zeng BH, Xu LH, Wang JY, Li MZ, Zeng MS, et al. Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma. J Transl Med. 2010;8:81. doi: 10.1186/1479-5876-8-81.

10. Dreilich M, Wanders A, Brattstrom D, Bergstrom S, Hesselius P, Wagenius G, et al. HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival. Dis Esophagus. 2006;19(4):224–231. doi: 10.1111/j.1442-2050.2006.00570.

11. Duong C, Greenawalt DM, Kowalczyk A, Ciavarella ML, Raskutti G, Murray WK, et al. Pretreatment gene expression profiles can be used to predict response to neoadjuvant chemoradiotherapy in esophageal cancer. Ann Surg Oncol. 2007;14(12):3602–3609. doi: 10.1245/s10434-007-9550-1.

12. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–2252. doi: 10.1056/NEJMra035010.

13. Finn OJ. Immune response as a biomarker for cancer detection and a lot more. N Engl J Med. 2005;353:1288–1290. doi: 10.1056/NEJMe058157.

14. Fitzgerald RC, di Pietro M, Ragunath K, Ang Y, Kang JY, Watson P, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014;63(1):7–42. doi: 10.1136/gutjnl-2013-305372.

15. Glickman JN, Yang A, Shahsafaei A, McKeon F, Odze RD. Expression of p53-related protein p63 in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders. Hum Pathol. 2001;32:1157–1165. doi: 10.1053/hupa.2001.28951.

16. Hiyoshi Y, Kamohara H, Karashima R, Sato N, Imamura Y, Nagai Y, et al. MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clin Cancer Res. 2009;15(6):1915–1922. doi: 10.1158/1078-0432.CCR-08-2545.

17. Huang YW, Liu JC, Deatherage DE, Luo J, Mutch DG, Goodfellow PJ, et al. Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer. Cancer Res. 2009;69(23):9038–9046. doi: 10.1158/0008-5472.CAN-09-1499.

18. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107.

19. Kan T, Sato F, Ito T, Matsumura N, David S, Cheng Y, et al. The miR-106b-25 polycistron, activated by genomic amplification, functions as an oncogene by suppressing p21 and Bim. Gastroenterology. 2009;136(5):1689–1700. doi: 10.1053/j.gastro.2009.02.002.

20. Kang M, Li Y, Liu W, Wang R, Tang A, Hao H, et al. miR-129-2 suppresses proliferation and migration of esophageal carcinoma cells through downregulation of SOX4 expression. Int J Mol Med. 2013;32(1):51–58.

21. Kaye PV, Haider SA, Ilyas M, James PD, Soomro I, Faisal W, et al. Barrett’s dysplasia and the Vienna classification: reproducibility, prediction of progression and impact of consensus reporting and p53 immunohistochemistry. Histopathology. 2009;54(6):699–712. doi: 10.1111/j.1365-2559.2009.03288.

22. Kilic A, Schuchert MJ, Luketich JD, Landreneau RJ, Lokshin AE, Bigbee WL, et al. Use of novel autoantibody and cancer-related protein arrays for the detection of esophageal adenocarcinoma in serum. J Thorac Cardiovasc Surg. 2008;136:199–204. doi: 10.1016/j.jtcvs.2008.01.012.

23. Kumar A, Chatopadhyay T, Raziuddin M, Ralhan R. Discovery of deregulation of zinc homeostasis and its associated genes in esophageal squamous cell carcinoma using cDNA microarray. Int J Cancer. 2007;120:230–242. doi: 10.1002/ijc.22246.

24. Lesnikova I, Lidang M, Hamilton-Dutoit S, Koch J. HER2/neu (c-erbB-2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimens. APMIS. 2009;117(10):737–745. doi: 10.1111/j.1600-0463.2009.02531.

25. Luthra R, Singh RR, Luthra MG, Li YX, Hannah C, Romans AM, et al. MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene. 2008;27(52):6667–6678. doi: 10.1038/onc.2008.256.

26. Mathe EA, Nguyen GH, Bowman ED, Zhao Y, Budhu A, Schetter AJ, et al. MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res. 2009;15(19):6192–6200. doi: 10.1158/1078-0432.CCR-09-1467.

27. Matsushima K, Isomoto H, Yamaguchi N, Inoue N, Machida H, Nakayama T, et al. MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells. J Transl Med. 2011;9:30. doi: 10.1186/1479-5876-9-30.

28. Motoori M, Takemasa I, Yamasaki M, Komori T, Takeno A, Miyata H, et al. Prediction of the response to chemotherapy in advanced esophageal cancer by gene expression profiling of biopsy samples. Int J Oncol. 2010;37(5):1113–1120.

29. Ohta M, Mimori K, Fukuyoshi Y, Kita Y, Motoyama K, Yamashita K, et al. Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer. Br J Cancer. 2008;98(2):410–417. doi: 10.1038/sj.bjc.6604124.

30. Pacha A, Rygiel AM, Westra W, Dijkgraaf MG, Rosmolen W, Visser M, et al. Su1181 A diagnostic DNA fish biomarker assay identifies HGD or EAC in Barrett esophagus. Elsevier Gastroenterol. 2012;142(5):S-445. doi: 10.1016/S0016-5085(12)61675-8

Abstract

References

Corresponding Author

Call For Paper Volume 12 Issue 10 November 2024

JMSCR Menu

Impact Factor SJIF 2024: 7.892

Crossref - DOI

Editorial Policy

Frequency of Publication

Submission of Articles

Search

Abstract

Call For Paper Volume 12 Issue 10 November 2024

JMSCR Menu

Impact Factor SJIF 2024: 7.892

Crossref - DOI

Editorial Policy

Frequency of Publication

Submission of Articles