Abstract
CD34, cytokeratin (CK) 19, cytokeratin (CK) 20, and Ki67 have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD34, CK19, CK20, and Ki67 expressions in colorectal cancer (CRC) and to evaluate their involvement in the progression of CRC. CD34, CK19, CK20, and Ki67 expressions were assessed in paraffin-embedded specimens collected from 152 cases of CRC and 30 paired normal colorectal tissues by immunohistochemistry. The relationships between CD34, CK19, CK20, and Ki67 expressions and CRC were evaluated. The association of CD34 and Ki67 protein expressions with the clinicopathological characteristics and the prognosis of CRC were subsequently assessed. CD34, CK19, CK20, and Ki67 expressed highly in CRC tissues relative to normal colorectal tissues. Using immunostaining scoring, a significant correlation of CD34 and Ki67 with the UICC staging and histo-differentiation of CRC was found (P < 0.05), but no such correlation of CK19 and CK20 with the UICC staging and histo-differentiation (P > 0.05). Meanwhile, no relationship of CD34, CK19, CK20, and Ki67 with the location of CRC was found (P > 0.05). Patients with high expressions of CD34 and Ki67 had the lowest survival (P < 0.05). The results suggest that concurrent expression of CD34 and Ki67 may be an important characteristic of CRC which may help in the prediction of CRC progression.
Similar content being viewed by others
References
Weitz J, Koch M, Debus J, et al. Colorectal cancer. Lancet. 2005;16:280–8.
You WC, Jin F, Devesa S, et al. Rapid increase in colorectal cancer rates in urban Shanghai, 1972–97, in relation to dietary changes. J Cancer Epidemiol Prev. 2002;7:143–6.
Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10–30. doi:10.3322/canjclin.55.1.10.
Woolf SH. The best screening test for colorectal cancer—a personal choice. N Engl J Med. 2000;343:1641–3. doi:10.1056/NEJM200011303432211.
Walsh JM, Terdiman JP. Colorectal cancer screening: scientific review. JAMA. 2003;289:1288–96. doi:10.1001/jama.289.10.1288.
Celis JE, Gromov P. Proteomics in translation cancer research: toward an integrated approach. Cancer Cell. 2003;3:9–15. doi:10.1016/S1535-6108(02)00242-8.
Ahlquist DA. Fecal occult blood testing for colorectal cancer. Can we afford to do this? Gastroenterol. Clin North Am. 1997;26:41–55. doi:10.1016/S0889-8553(05)70282-X.
Collins JF, Lieberman DA, Durbin TE, et al. Accuracy of screening for fecal occult blood on a single stool sample obtained by digital rectal examination: a comparison with recommended sampling practice. Ann Intern Med. 2005;142:81–5.
Geenen JE, Schmitt MG Jr, Wu WC, et al. Major complications of coloscopy: bleeding and perforation. Am J Dig Dis. 1975;20:231–5. doi:10.1007/BF01070726.
Silvis SE, Nebel O, Rogers G, et al. Endoscopic complications: results of the 1974 American Society for gastrointestinal endoscopy survey. J Am Med Assoc. 1976;235:928–30. doi:10.1001/jama.235.9.928.
Winawer S, Fletcher R, Rex D, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale-update based on new evidence. Gastroenterology. 2003;124:544–60. doi:10.1053/gast.2003.50044.
Roessler M, Rollinger W, Mantovani-Endl L, et al. Identification of PSME3 as a novel serum tumor marker for colorectal cancer by combining two-dimensional polyacrylamide gel electrophoresis with a strictly mass spectrometry-based approach for data analysis. Mol Cell Proteomics. 2006;5:2092–101. doi:10.1074/mcp.M600118-MCP200.
American Society of Clinical Oncology: clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol. 1996;14:2843–77.
Bast RC Jr, Ravdin P, Hayes DF, et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1865–78.
da Silva BB, Pires CG, Dos Santos AR, et al. Effects of raloxifene on Ki-67 and CD34 antigen expression in breast cancer. Gynecol Obstet Invest. 2008;67:103–8. doi:10.1159/000165512.
Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6. doi:10.1093/jnci/82.1.4.
Weidner N, Semple JP, Welche WR, et al. Tumor angiogenesis and metastasis correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.
Folkman J. Angiogenesis and breast cancer. J Clin Oncol. 1994;12:441–3.
Nieto Y, Woods J, Nawaz F, et al. Prognostic analysis of tumour angiogenesis, determined by microvessel density and expression of vascular endothelial growth factor, in high-risk primary breast cancer patients treated with high-dose chemotherapy. Br J Cancer. 2007;97:391–7. doi:10.1038/sj.bjc.6603875.
Vieira SC, Silva BB, Pinto GA, et al. CD34 as a marker for evaluating angiogenesis in cervical cancer. Pathol Res Pract. 2005;201:313–8. doi:10.1016/j.prp.2005.01.010.
Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long term follow-up. Am J Surg Pathol. 2005;29:522–68.
Li Z, Zhao X, Bai S, et al. Proteomics identification of cyclophilin a as a potential prognostic factor and therapeutic target in endometrial carcinoma. Mol Cell Proteomics. 2008;7:1810–23. doi:10.1074/mcp.M700544-MCP200.
Kreisberg JI, Malik SN, Prihoda TJ, et al. Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Cancer Res. 2004;64:5232–6. doi:10.1158/0008-5472.CAN-04-0272.
Feng YZ, Shiozawa T, Miyamoto T, et al. Overexpression of hedgehog signaling molecules and its involvement in the proliferation of endometrial carcinoma cells. Clin Cancer Res. 2007;13:1389–98. doi:10.1158/1078-0432.CCR-06-1407.
Fox SB, Gatter KC, Bicknell R, et al. Relationship of endothelial cell proliferation to tumor vascularity in human breast cancer. Cancer Res. 1993;53:4161–3.
Vartanian RK, Weidner N. Correlation of intratumoral endothelial cell proliferation with microvessel density (tumor angiogenesis) and tumor cell proliferation in breast carcinoma. Am J Pathol. 1994;144:1188–94.
Rudolph P, Peters J, Lorenz D, et al. Correlation between mitotic and Ki-67 labeling indices in paraffin-embedded carcinoma specimens. Hum Pathol. 1998;29:1216–22. doi:10.1016/S0046-8177(98)90248-9.
Leek RD. The prognostic role of angiogenesis in breast cancer. Anticancer Res. 2001;21:4325–31.
Acknowledgments
This study was supported by the financial grants from the Shanghai Science and Technology Development Fund (No. 05DJ14010), the Major Basic Research Program of Shanghai (No. 07DZ19505), and the National 973 Basic Research Program of China (No. 2008CB517403).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ma, YL., Peng, JY., Zhang, P. et al. Immunohistochemical analysis revealed CD34 and Ki67 protein expression as significant prognostic factors in colorectal cancer. Med Oncol 27, 304–309 (2010). https://doi.org/10.1007/s12032-009-9210-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-009-9210-3