Prognostic Value of IMP3 and Cyclin D1 Expression in Patients with Colorectal Cancer

Mohamed, Salem Youssef; Hafez, Abeer; Elwan, Amira; Abdelhamid, Mohamed I.; Ahmed, Nabila Hassan; Abdelmaksoud, Bader A.; Abdelbary, Abeer M

doi:10.30476/mejc.2021.85085.1258

Prognostic Value of IMP3 and Cyclin D1 Expression in Patients with Colorectal Cancer

Document Type : Original Article(s)

Authors

Salem Youssef Mohamed ¹

Abeer Hafez ²

Amira Elwan ³

Mohamed I. Abdelhamid ⁴

Nabila Hassan Ahmed ⁵

Bader A. Abdelmaksoud ³

Abeer M Abdelbary ²

¹ Gastroenterology and Hepatology Unit, Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt

² Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt

³ Clinical Oncology Department, Zagazig University, Zagazig, Egypt

⁴ General Surgery Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt

⁵ Tropical Medicine Department, Zagazig University, Zagazig, Egypt

https://doi.org/10.30476/mejc.2021.85085.1258

Abstract

Background: Colorectal cancer (CRC) is known to be the third most frequently diagnosed cancer and the fourth leading cause of cancer death worldwide. In Egypt, colorectal carcinoma is considered the 7th prevalent cancer, accounting for 3.47% of male cancers and 3% of female malignancies. A localized CRC can be entirely cured via surgical resection. Metastasis remains the leading cause of cancer mortality. IMP3 is an independent prognostic biomarker that expects metastasis and poor prognosis in CRC. The upregulation of nuclear cyclin D1 plays an essential role in pathogenesis and metastases of CRC. We aimed to investigate the expression of IMP3 and cyclin D1 in colorectal carcinoma and their correlation with other clinicopathological features.
Method: In this retrospective cohort study, 80 formalin-fixed and paraffin-embedded blocks of CRC were obtained from the subjects. The immunohistochemical expression of IMP3 and cyclin D1 were examined and found to be correlated with clinical-pathological parameters and the outcome of the patients.
Results: Overexpression of IMP3 and cyclin D1 was noted in 68.75% and 56.25%, respectively. IMP3 expression was significantly correlated with tumor grade (P < 0.001), tumor, node, and metastases (TNM) stage (P = 0.040), and lymphovascular invasion (P = 0.005); cyclin D1 was significantly associated with TNM stage (P < 0.001), lymph node (LN) metastasis (P < 0.001), and distant metastasis (DM) (P = 0.004); cyclin D1 was significantly correlated with TNM stage (P < 0.001), LN metastasis (P < 0.001), and DM (P = 0.004).
Conclusion: IMP3 and cyclin d1 were associated with poor prognosis in CRC, w hich makes them attractive targets for anticancer drug development.

Keywords

IMP3

Cyclin D1

Colorectal cancer

Recurrence

Survival

How to cite this article:

Mohamed SY, Hafez A, Elwan A, Abdelhamid MI, Ahmed NH, Abdelmaksoud BA, et al. Prognostic value of IMP3 and cyclin D1 expression in patients with colorectal cancer. Middle East J Cancer. 2022;13(1):57-66. doi: 10.30476/mejc.2021. 85085.1258.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30. doi:10.3322/caac.21442 .
2. Metwally IH, Shetiwy M, Elalfy AF, Abouzid A, Saleh SS, Hamdy M. Epidemiology, and survival of colon cancer among Egyptians: a retrospective study. J Coloproctol (Rio J). 2018;38(1):24-9. doi: 10.1016/j. jcol.2017.09.418.
3. Isella C, Terrasi A, Bellomo SE, Petti C, Galatola G, Muratore A, et al. Stromal contribution to the colorectal cancer transcriptome. Nat Genet. 2015;47(4):312-9. doi:10.1038/ng.3224.
4. House MG, Kemeny NE, Gonen M, Fong Y, Allen PJ, Paty PB, et al. Comparison of adjuvant systemic chemotherapy with or without hepatic arterial infusional chemotherapy after hepatic resection for metastatic colorectal cancer. Ann Surg. 2011;254(6):851-6. doi:10.1097/SLA.0b013e31822f4f88.
5. Bell JL, Wachter K, Muhleck B, Pazaitis N, Kohn M, Lederer M, et al. Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression? Cell Mol Life Sci. 2013;70(15):2657-75. doi:10.1007/s00018-012-1186-z.
6. Mueller-Pillasch F, Pohl B, Wilda M, Lacher U, Beil M, Wallrapp C, et al. Expression of the highly conserved RNA binding protein KOC in embryogenesis. Mech Dev. 1999;88(1):95-9. doi:10.1016/s0925-4773(99)00160-4.
7. Findeis-Hosey JJ, Xu H. Insulin-like growth factor II-messenger RNA-binding protein-3 and lung cancer. Biotech Histochem. 2012;87(1):24-9. doi:10.3109/ 10520295.2011.591831.
8. Yuan RH, Wang CC, Chou CC, Chang KJ, Lee PH, Jeng YM, et al. Diffuse expression of RNA-binding protein IMP3 predicts high-stage lymph node metastasis and poor prognosis in colorectal adenocarcinoma. Ann Surg Oncol. 2009; 16:1711–9. doi: 10.1245/s10434-009-0446-0.
9. Yasui M, Yamamoto H, Ngan CY, Damdinsuren B, Sugita Y, Fukunaga H, et al. Antisense to cyclin D1 inhibits vascular endothelial growth factor-stimulated growth of vascular endothelial cells: implication of tumor vascularization. Clin Cancer Res. 2006;12(15): 4720–9. doi: 10.1158/1078-0432.ccr-06-0614.
10. Alao JP. The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Mol Cancer. 2007;6:24. doi:10.1186/1476-4598-6-24.
11. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29(4):577-80. doi:10.1177/29.4.6166661.
12. Chisté M, Alexis J, Recine M. IMP3 expression in serous tumors of the ovary. Appl Immunohistochem Mol Morphol. 2014;22(9):658-62. doi:10.1097/PAI. 0000000000000021.
13. 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. 2011;2:10. doi:10.1186/2042-6410-2-10.
14. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin.2015;65:87-108. doi: 10.3322/caac.21262.
15. Lochhead P, Imamura Y, Morikawa T, Kuchiba A, Yamauchi M, Liao X, et al. Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavorable prognosis in colorectal cancer. Eur J Cancer. 2012;48: 3405-13. doi: 10.1016/j.ejca. 2012.06.021.
16.Huang X, Wei Q, Liu J, Niu H, Xiao G, Liu L. Analysis of IMP3 expression in primary tumor and stromal cells in patients with colorectal cancer. Oncol Lett. 2017;14(6):7304-10. doi:10.3892/ol.2017.7161.
17. Wei Q, Huang X, Fu B, Liu J, Zhong L, Yang Q, et al. IMP3 expression in biopsy specimens of colorectal cancer predicts lymph node metastasis and TNM stage. Int J Clin Exp Pathol. 2015;8(9):11024-32. doi: 10. 3892/or.2017.6072.
18.Bahnassy AA, Zekri AR, El-Houssini S, El-Shehaby AM, Mahmoud MR, Abdallah S, et al. Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients. BMC Gastroenterol. 2004;4:22. doi:10.1186/1471-230X-4-22.
19. Salem AM, Elfeky MA, Nawar N, Alattar AZ, Elekiabi OA, Elaidy MM. Prognostic value of combined; cox-2, cyclin D1 and P21 expression in colorectal cancer (CRC) patients: An immunohistochemical study. Open J Pathol. 2018;8(3):106-21. doi:10.4236/ojpathology. 2018.83013.
20. Von Stockmar-Von Wangenheim CA, Mönig SP, Schneider PM, Landsberg S, Drebber U, Hölscher AH, et al. p16, cyclin D1 and Rb expression in colorectal carcinomas: Correlations with clinico-pathological parameters and prognosis. Mol Med Rep. 2008;1(1):27-32. doi:10.3892/mmr.1.1.27.
21. Al-Maghrabi J, Mufti S, Gomaa W, Buhmeida A, Al-Qahtani M, Al-Ahwal M. Immunoexpression of cyclin D1 in colorectal carcinomas is not correlated with survival outcome. J Microsc Ultrastruct. 2015;3(2):62-7. doi: 10.1016/j.jmau. 2015.01.001.
22. Holland TA, Elder J, McCloud JM, Hall C, Deakin M, Fryer AA, et al. Subcellular localization of cyclin D1 protein in colorectal tumors is associated with p21(WAF1/CIP1) expression and correlates with patient survival. Int J Cancer. 2001;95(5):302-6. doi:10.1002/1097-0215(20010920)95:5<302::aid-ijc1052>3.0.co;2-#.
23. Ogino S, Nosho K, Irahara N, Kure S, Shima K, Baba Y, et al. A cohort study of cyclin D1 expression and prognosis in 602 colon cancer cases. Clin Cancer Res. 2009;15(13):4431-8. doi:10.1158/1078-0432.CCR-08-3330.
24. Li D, Yan D, Tang H, Zhou C, Fan J, Li S, et al. IMP3 is a novel prognostic marker that correlates with colon cancer progression and pathogenesis. Ann Surg Oncol. 2009;16(12):3499-506. doi:10.1245/s10434-009-0648-5.
25.van de Velde CJ, Aristei C, Boelens PG, Beets Tan RG, Blomqvist L, Borras JM, et al. EURECCA colorectal: Multidisciplinary mission statement on better care for patients with colon and rectal cancer in Europe. Eur J Cancer. 2013;49(13):2784-90. doi:10.1016/j.ejca.2013.04.032.
26.Ahmed S, Johnson K, Ahmed O, Iqbal N. Advances in the management of colorectal cancer: From biology to treatment. Int J Colorectal Dis. 2014; 29: 1031-42. doi:10.1007/s00384-014-1928-5.