Annals of Surgical Treatment and Research

The Korean Surgical Society (대한외과학회)
권호 표지

Clinical Correlation of iNOS and p53 Expression in Colorectal Cancer

대장 직장암에서 Inducible Nitric Oxide Synthase 및 p53 발현의 임상적 관련성

Jeong, Seong-Hun;Kim, Cheong-Yong;Kee, Keun-Hong
정성훈;김정용;기근홍

  • Published : 20020100
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Abstract

Purpose: Nitric oxide (NO) is synthesized from the amino acid L-arginine by nitric oxide synthase (NOS) which exists as three isoforms, the calcium-dependent endothelial NOS and neuronal NOS, and a calcium-independent inducible NOS. NO has been studied in a variety of human cancers and is implicated in both tumor promotion and inhibition. NO cause p53 mutation in human cells and mutations of p53 are the most common genetic abnormality yet found in human cancers. Aims of this study is to investigate the correlation of iNOS and p53 expression in colorectal cancer, and to evaluate its clinicopathological siginificance with the expression of these proteins. Methods: 125 patients, who received curative resection of colorectal cancer from 1992 to 1996, were analyzed retrospectively. The monoclonal antibody to the iNOS (Transduction Laboratories.), the monoclonal antibody to the mutant p53 (Dako Co.) were used for the immunohistochemical analysis. Normal colorectal tissue were assayed in 45 cases The relationship between mutant p53 and iNOS was lnvestigated. Results: When iNOS expression were detected in specimens, positive rate of mutant p53 were 72.4%. When mutant p53 expression were detected in specimens, positive rate of iNOS expression were 65.8%(P<0.05). Positive rate of iNOS, mutant p53 in tumor size were 51%, 56% below 4 cm and 60%, 63% in 4$\sim$8 cm and 47%, 67% above 8 cm, Positive rate of iNOS, mutant p53 in Dukes' stage were 55%, 55% in stage B and 56%, 67% in stage C. Positive rate of iNOS, mutant p53 in histologic differentiation were 55%, 55% in well-differentiation and 61%, 66% in moderate differentiation and 35%, 48% in poor-differentiation. There was no difference in each Dukes stage between iNOS expression or p53 mutation and postop five year survival rate. Positive rate of iNOS, mutant p53 in normal tissue were 22%, 32%. Conclusion: The prevalence of iNOS expression and p53 mutation has been found in exceeding 50% of cases. There was a significant correlation between iNOS expression and p53 mutation in colorectal cancer. No correlation was found between iNOS expression or p53 mutation and clinicopathologic parameters.

Keywords

References

  1. Stefan A, William GM, William PB, Emanuela FB, Mofolusara OO, Sean MO, et al. Frequent nitric oxide synthase-2 expression in human colon adanomas: Implication for tumor angiogenesis and colon cancer progression. Cancer Research 1998;58:334-41.
  2. Lindy L. Thomsen, James MJS, Peter T, Richard GK, Amanda JK, et al. Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: Studies with 1,400 W, a Novel inhibitor. Cancer Research 1997;57:3300-4.
  3. Jenkeins DC, Charles IG, Baylis SA, Lelchuk R, Radomski MW & S. Moncada, Human colon cancer cell lines show a diverse pattern of nitric oxide synthase gene expression and nitric oxide generation, Br J Cancer 1994;70:847-9. https://doi.org/10.1038/bjc.1994.409
  4. Marek WR, David CJ, Lesley H, Salvador M. Human colorectal adenocarcinoma cells: Differential nitric oxide synthesis determines their ability to aggregate platelets. Cancer Research 1991;51:6073-8.
  5. Masayuki K, Takashi M, Yasuhiro T, Akihiko D, Yasuo M, Ryuichi M, et al. Nitric oxide synthase expression and nitric oxide production in human colon carcinoma tissue. J Surg Oncol 1999;70:222-9. https://doi.org/10.1002/(SICI)1096-9098(199904)70:4<222::AID-JSO5>3.0.CO;2-G
  6. Kim HO, Kim WH, Bae SI, Lee HW, Kim CJ, Hong SY, et al. Effect of wild-type p53 gene transfection into human colon cancer cell line. Korean Cancer Assoc 1999;31:367-76.
  7. Stefan A, Hussain SP, Curtis CH. Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression. FASEB 1997;11:443-8.
  8. Jenkins DC, Charles IG, Thonsen LL, Moss DW, Holmes LS, Baylis SA, et al. Roles of nitric oxide in tumor growth. Medical Science 1995;92:4392-6.
  9. Hironori F, Tsutomu O, Atsushi H, Alessandro W, Junkoh Y, Hiroyasu E. Inducible nitric oxide synthase in a human glioblastoma cell line. J Neurochem 1995;64:85-91. https://doi.org/10.1046/j.1471-4159.1995.64010085.x
  10. Kitano H, Kitanishi T, Nakanishi Y, Suzuki M, Takeeuchi E, Yazawa Y, et al. Expression of inducible nitric oxide synthase in human thyroid papillary carcinomas. Thyroid 1999;9:113-7. https://doi.org/10.1089/thy.1999.9.113
  11. Joseph S, Leibovich, Peter JP, Timothy WF, Lisa AH. Production of angiogenic activity of human monocytes requires an 1-arginine/nitric oxide-synthase-dependent effector mechanism. Cell Biol 1994;91:4190-4.
  12. Shabbir M, Vikram JSC, Steven TFC, Sing SN, Yee WC, Abu R. Nitric oxide synthase activity and expression in human colorectal cancer. Carcinogenesis 1996;17:1171-4. https://doi.org/10.1093/carcin/17.5.1171
  13. Moncada S, Palmer RMJ, Higgs EA. Nitiric Oxide: Physiology, Pathophysiology, and Phamacology. Pharmacological Reviews 1991;43:109-41.
  14. Park JS. Endothelium-derived nitric oxide. J Korean Soc Vascular Surg 1998;14:179-93.
  15. Lindy L. Thomsen. David W. Miles. Role of nitric oxide in tumor progression: Lessons from human tumours. Cancer and Metastasis Reviews 1998;17:107-8. https://doi.org/10.1023/A:1005912906436
  16. Limin L, Robert GK, James A, Isaiah JF. Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells, Cancer Research 1991;51:2531-5.
  17. Gillian MT, Vivien EP, David JC. Inhibition of nitric oxide synthase induces a selective reduction in tumor blood flow that is reversible with L-arginine. Cancer Research 1997;57:948-55.
  18. Brennan PA, Palacios-Callender M, Umar T, Hughes D, Spedding AV, Zaki GA. Correlation between typr II nitric oxide synthase and p53 expression in oral squamous cell carcinoma. Br J Oral Maxillofacial Surg 2000;38:627-32. https://doi.org/10.1054/bjom.2000.0540
  19. Keping X, Zhongyun D, Isaiah JF. Activation of nitric oxide synthase gene for inhibition of cancer metastasis. J Leukocyte BioI 1996;59:797-803.
  20. Michael BK, Onyine O, David S, Bert Y, Ruth WC. Participation of p53 protein in the cellular response to DNA Damage. Cancer Research 1991;51:6304-11.
  21. Kathleen F, Stefan A, Shawn EL, Rachel BK, Elisa AS, Wendy CW, et al. Nitric Oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase expression by wild-type p53. Med Sci 1996;93:2442-7.
  22. Monica H, David S, Bert V, Curtis CH. p53 mutation in human cancers. Science 1991;253:49-53. https://doi.org/10.1126/science.1905840
  23. Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutation in the p53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis. Cancer Research 1994;54:4855-78.