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hMSH2 and nm23 Expression in Sporadic Colorectal Cancer and its Clinical Significance

  • Wu, Hong-Wei ;
  • Gao, Li-Dong ;
  • Wei, Guang-Hui
  • Published : 2013.03.30

Abstract

Objective: To study the expression of the mismatch repair proteins hMSH2 and nm23 in sporadic colorectal cancer, determine any inter-relationship, and further investigate any clinical significance. Methods: Expression of hMSH2 and nm23 proteins was assessed in 87 colorectal cancer tissues by SP immunohistochemistry, with analysis of survival using follow-up data. Results: In the sporadic colorectal cancer tissues, nm23 protein expression appeared independent of the histological type (P>0.05), but correlated with the invasion depth and lymphatic metastasis (P<0.05). In contrast, hMSH2 protein expression was not significantly correlated with these clinicopathologic features (P>0.05), although it positively correlated with that of nm23 protein in the sporadic colorectal cancers (rs=0.635, P<0.05). Combined expression of the two was found to be related with invasion depth, lymphatic metastasis and prognosis of sporadic colorectal cancer (P<0.05). Conclusion: nm23 protein level was related with the degree of malignancy, and could be used as an index to predict the invasion and metastasis potential. The expression of hMSH2 protein is positively correlated that of nm23 protein, and the combined expression of the two has certain guiding significance for the prognosis of sporadic colorectal cancer.

Keywords

Sporadic colorectal cancer;hMSH2;nm23;immunohistochemistry;prognosis

References

  1. Chen WC, Lin MS, Zhang BF, et al (2007). Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray. World J Gastroenterol, 13, 699-708. https://doi.org/10.3748/wjg.v13.i5.699
  2. Duncop MG, Farrington SM, Nicholl I, et al (2000). Population carrier frequency of hMSH2 and hMLH1 mulation. Br J Cancer, 83, 1643-5. https://doi.org/10.1054/bjoc.2000.1520
  3. Dursun A, Akyürek N, Günel N, Yamaç D (2002). Prognostic implication of nm23-H1 expression in colorectal carcinomas. Pathology, 34, 427-32. https://doi.org/10.1080/0031302021000009342
  4. Gafa R, Maestri I, Matteuzzi M, et al (2000). Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability. Cancer, 89, 2025-37. https://doi.org/10.1002/1097-0142(20001115)89:10<2025::AID-CNCR1>3.0.CO;2-S
  5. Gradia S, Acharya S, Fishel R (1997). The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch. Cell, 91, 995-1005. https://doi.org/10.1016/S0092-8674(00)80490-0
  6. Gryfe R, Gallinger S (2001). Microsatellite instability, mismatch repair deficiency, and colorectal cancer. Surgery, 130, 17-20. https://doi.org/10.1067/msy.2001.112738
  7. Hsieh P, Yamane K (2008). DNA mismatch repair: molecular mechanism, cancer, and ageing. Mech Ageing Dev, 129, 391-407. https://doi.org/10.1016/j.mad.2008.02.012
  8. Iyer RR, Pluciennik A, Burdett V, Modrich PL (2006). DNA mismatch repair: functions and mechanisms. Chem Rev, 106, 302-20. https://doi.org/10.1021/cr0404794
  9. Kolodner RD, Hall NR, Lipford J, et al (1995). Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlhl mutations. Cancer Res, 55, 242-8.
  10. Leone A, Flatow U, Richter KC, et al (1991). Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell, 65, 25-35. https://doi.org/10.1016/0092-8674(91)90404-M
  11. Leone A, McBride OW, Weston A, et al (1991). Somatic allelic deletion of nm23 in human cancer. Cancer Res, 51, 2490-3.
  12. Lipkin SM, Wang V, Jacoby R, et al (2000). MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet, 24, 27-35. https://doi.org/10.1038/71643
  13. Loeb LA (1994). Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Res, 54, 5059-63.
  14. Marsischky GT, Filosi N, Kane MF, Kolodner R (1996). Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev, 10, 407-20. https://doi.org/10.1101/gad.10.4.407
  15. Okada K, Urano T, Goi T, et al (1994). Isolation of human nm23 genomes and analysis of loss heterozygosity in primary colorectal carcinomas using a specific genomic probe. Cancer Res, 54, 3879-82.
  16. Overbeek LI, Ligtenberg MJ, Willems RW, et al (2008). Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting. Am J Surg Pathol, 32, 1246-51. https://doi.org/10.1097/PAS.0b013e31816401bb
  17. Rhyu MS (1996). Molecular mechanisms underlying hereditary nonpolyposis colorectal carcinoma. J Natl Cancer Inst, 88, 240-51. https://doi.org/10.1093/jnci/88.5.240
  18. Sarasin A, Stary A (1997). Human cancer and DNA repairdeficient diseases. Cancer Detect Prev, 21, 406-11.
  19. Steeg PS, Bevilacqua G, Kopper L, et al (1988). Evidence for a novel gene associated with low tumor metastatic potential. J Nat Cancer Inst, 80, 200-4. https://doi.org/10.1093/jnci/80.3.200
  20. Suzuki E, Ota T, Tsukuda K, et al (2004). nm23-H1 reduces in vitro cell migration and the liver metastatic potential of colon cancer cells by regulation myosin light chain phosphorylation. Int J Cancer, 108, 207-11. https://doi.org/10.1002/ijc.11546

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