Profil Ekspresi HER2 Dan Cyclin D1 Pada Pasien Adenokarsinoma Kolorektal Di RSUP Dr.Kariadi Semarang

  • Devia Eka Listiana
  • Hermawan Istiadi Kelompok Staf Medik Patologi Anatomi, RSUP Dr.Kariadi Semarang
  • Viena Alodia Bagian Patologi Anatomi, Fakultas Kedokteran Universitas Diponegoro

Abstract

Latar belakang: Adenokarsinoma kolorektal merupakan keganasan yang paling sering ditemui dengan mortalitas ketiga terbanyak. Beberapa ekspresi protein diketahui berhubungan dengan karsinogenesis adenokarsinoma kolorektal, diantaranya adalah HER2 dan Cyclin D1. HER2 dan Cyclin D1 merupakan proto-onkogen yang dapat mengalami overekspresi pada adenokarsinoma kolorektal. Penelitian ini bertujuan untuk mengetahui profil ekspresi HER2 dan Cyclin D1 dan hubungannya dengan parameter klinikopatologis pasien adenokarsinoma kolorektal.

Metode Penelitian: Penelitian ini merupakan penelitian observasional analitik dengan desain cross sectional dengan sampel 40 blok paraffin pasien adenokarsinoma kolorektal di RSUP dr. Kariadi Semarang, Indonesia pada periode Januari 2019 hingga Desember 2019. Parameter klinikopatologis yang diamati meliputi : lokasi tumor, kedalaman infiltrasi tumor, derajat histologi serta metastasis pada kelenjar getah bening (KGB) regiona serta ekspresi HER2 dan Cyclin D1 dengan imunohistokimia.

Hasil: Sebanyak 15% pasien memiliki ekspresi HER2 equivocal dan 5% pasien HER2 positif, sedangkan profil ekspresi Cyclin D1 menunjukkan low expresion sebanyak 60%, sedangkan high expresion sebanyak 40% sampel. Ekspresi HER2 positif ditemukan pada pasien dengan lokasi rectosigmoid dan rectum, infiltrasi serosa dan derajat histologi low grade, namun tidak bermakna. Ekspresi Cyclin D1 yang tinggi ditemukan pada pasien dengan lokasi rectosigmoid, infiltrasi serosa, derajat histologi low grade, tidak berbeda bermakna.

Kesimpulan: Ekspresi HER2 dan Cyclin D1 memiliki hubungan yang tidak bermakna dengan parameter klinikopatologik pasien adenokarsinoma kolorektal.

Kata kunci: adenokarsinoma kolorektal, HER2, Cyclin D1

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References

Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76:182–8.

Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer?: incidence , mortality , survival , and risk factors. Gastroenterol Rev. 2019;14(2):89–103.

Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2016;0:1–9.

Pedoman nasional pelayanan kedokteran tatalaksana kanker kolorektal 2018 [Internet]. Kementerian Kesehatan Republik Indonesia. 2018 [cited 2019 Oct 22]. Available from: http://kanker.kemkes.go.id/guidelines/PNPKkolorektal.pdf

Afriani N, Krisnuhoni E, Rahadiani N. Ekspresi HER2/neu(c-ErbB2) pada Kanker Kolorektal. MKA. 2014;37(2):48–53.

Seo AN, Kwak Y, Kim D, Kang S, Choe G, Kim WH, et al. HER2 Status in Colorectal Cancer?: Its Clinical Significance and the Relationship between HER2 Gene Amplification and Expression. PLoS One. 2014;9(5):e98528.

Albasri AM, Elkablawy MA, Ansari A, Alhujaily AS. Prognostic Significance of Cyclin D1 Over-expression in Colorectal Cancer?: An Experience from Madinah , Saudi Arabia. Asian Pac J Cancer Prev. 2019;20(8):2471–6.

Bahnassy A, Zekri AN, El-Houssini S, El-Shehaby A, Mahmoud MR, Abdallah S, et al. Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients. BMC Gastroenterol. 2004;4(22).

Li Y, Wei J, Xu C, Zhao Z, You T. Prognostic Significance of Cyclin D1 Expression in Colorectal Cancer?: A Meta-Analysis of Observational Studies. PLoS One. 2014;9(4):20–5.

Tai W, Mahato R, Cheng K. The role of HER2 in cancer therapy and targeted drug delivery. J Control Release. 2010;146(3):264–75.

Siena S, Sartore-Bianchi A, Marsoni S, Hurwitz HI, Mccall SJ, Srock S, et al. Targeting the human epidermal growth factor receptor 2 ( HER2 ) oncogene in colorectal cancer. Ann Oncol. 2018;29:1108–19.

Schuell B, Gruenberger T, Scheithauer W, Zielinski CC, Wrba F. HER 2/neu protein expression in colorectal cancer. BMC Cancer. 2006;6(123).

Suma S, Ummerali SK. HER2/neu Expression in Colorectal Cancers. Int J Contemp Med Res. 2017;4(6):1240–3.

Kaptain S, Tan LK, Chen B. Her-2/neu and breast cancer. Diagn Mol Pathol. 2001;10:139–52.

SiShi L, Buchbinder E, Wu L, Bjorge JD, Fujita DJ, Zhu S. EGFR and HER2 levels are frequently elevated in colon cancer cells. Discov Reports. 2014;1(1):e1.

Ross JS, McKenna BJ. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 2001;19(5):554–68.

Pappas A, Lagoudianakis E, Seretis C, Tsiambas E, Koronakis N, Toutouzas K, et al. Clinical role of HER-2/neu expression in colorectal cancer. J BUON. 2013;18(1):98–104.

Sayadnejad N, Firouzjahi A, Shafaee S, Golshahi H, Sokouti Z. 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.

Kavanagh DO, Chambers G, Grady LO, 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):1–6.

Wu Q, Sun G. Expression of COX-2 and HER-2 in colorectal cancer and their correlation. World J Gastroenterol. 2015;21(20):6206–14.

Ramieri MT, Murari R, Botti C, Pica E, Zotti G, Alo PL. Detection of HER2 Amplification Using the SISH Technique in Breast, Colon, Prostate, Lung and Ovarian Carcinoma. Anticancer Res. 2010;30(4):1287–92.

Conradi LC, Styczen H, Sprenger T, Wolff HA, Rodel C, Nietert M, et al. Frequency of HER-2 Positivity in Rectal Cancer and Prognosis. Am J Surg Pathol. 2013;37(4):522–31.

Heppner BI, Behrens H, Balschun K, Haag J, Kruger S, Becker T, et al. HER2/neu testing in primary colorectal carcinoma. Br J Cancer. 2014;111:1977–84.

Kruszewski WJ, Rzepko R, Ciesielski M, Szefel J, Zielinski J, Szajewski M, et al. Expression of HER2 in colorectal cancer does not correlate with prognosis. Dis Markers. 2010;29:207–12.

Cheng G, Mei Y, Pan X, Liu M, Wu S. Expression of HER2 / c-erbB-2 , EGFR protein in gastric carcinoma and its clinical significance. Open Life Sci. 2019;14(1):119–25.

Volpi E V, Bridger JM. FISH glossary: an overview of the fluorescence in situ hybridization technique. Biotechniques. 2008;45(4):385–6.

Ross JS, Fakih M, Ali SM, Elvin JA, Schrock AB, Suh J, et al. Targeting HER2 in Colorectal Cancer?: The Landscape of Amplification and Short Variant Mutations in ERBB2 and ERBB3. Cancer. 2018;124(7):1358–73.

Bali A, O’Brien PM, Edwards LS, Sutherland RL, Hacker NF, Henshall SM. Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clin Cancer Res. 2004;10(15):5168–77.

Alao JP. The regulation of cyclin D1 degradation?: roles in cancer development and the potential for therapeutic invention. Mol Cancer. 2007;6(24):1–16.

Chen W, Lin M, Zhang B, Fang J, Zhou Q, Hu Y, et al. Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray. World J Gastroenterol. 2007;13(5):699–708.

Holland TA, Elder J, McCloud JM, Hall C, Deakin M, Fryer AA, et al. Subcellular Localisation of Cyclin D1 Protein in Colorectal Tumours Is Associated With p21(WAF1/CIP1) Expression and Correlates With Patient Survival. Int J Cancer. 2001;95(5):302–6.

Tetsu O, Mccormick F. ? - Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 1999;398:422–426.

Shtutman M, Zhurinsky J, Simcha I, Albanese C, D’amico M, Pestell R, et al. The cyclin D1 gene is a target of the b-cateninyLEF-1 pathway. Proc Natl Acad Sci. 1999;96(May):5522–7.

Ogino S, Nosho K, Irahara N, Kure S, Shima K, Baba Y, et al. A Cohort Study of Cyclin D1Expression and Prognosis in 602 Colon Cancer Cases. Clin Cancer Res. 2009;15(13):4431–9.

Nassrat FL, Ali HH, Qasim BJ. Immunohistochemical expression of cyclin D1 in colorectal adenomas?: a clinicopathological study. Kasr Al Ainy Med J. 2016;22(3):115–22.

Wangefjord S, Manjer J, Gaber A, Nodin B, Eberhard J, Jirström K. Cyclin D1 expression in colorectal cancer is a favorable prognostic factor in men but not in women in a prospective , population-based cohort study. Biol Sex Differ [Internet]. 2011;2(1):10. Available from: http://www.bsd-journal.com/content/2/1/10

Yaylim-eraltan ?, Arikan S, Yildiz Y, Cacina C, Ergen HA, Tuna G, et al. The Influence of Cyclin D1 A870G Polymorphism on Colorectal Cancer Risk and Prognosis in a Turkish Population. Anticancer Res. 2010;30:2875–80.

McKay JA, Douglas JJJ, Ross VG, Curran S, Murray GI, Cassidy J, et al. Cyclin D1 Protein Expression And Gene Polymorphism In Colorectal Cancer. Int J Cancer. 2000;88:77–81.

Published
2021-03-23
Section
Original Article