COLORECTAL CANCER

Low level microsatellite instability may be associated with reduced cancer specific survival in sporadic stage C colorectal carcinoma

C M Wright¹, O F Dent², R C Newland³, M Barker¹, P H Chapuis², E L Bokey², J P Young¹, B A Leggett¹, J R Jass⁴, G A Macdonald⁵

¹ Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital Research Foundation Clinical Research Centre, Brisbane, Australia
² Department of Colorectal Surgery, Concord Hospital and the University of Sydney, Australia
³ Department of Anatomical Pathology, Concord Hospital and the University of Sydney, Australia
⁴ Department of Pathology, The University of Queensland, Queensland Institute of Medical Research, Brisbane, Australia
⁵ Department of Medicine, The University of Queensland, and the Division of Population Health and Clinical Sciences, Queensland Institute of Medical Research, Brisbane, Australia

Correspondence to:
Correspondence to:
Dr C Wright
The Royal Prince Alfred Medical Centre, 419/100 Carillon Ave, Newtown, NSW 2042, Australia; carolinewright{at}hn.ozemail.com.au

Background: Colorectal cancers (CRCs) may be categorised according to the degree of microsatellite instability (MSI) exhibited, as MSI-high (MSI-H), MSI-low (MSI-L), or microsatellite stable (MSS). MSI-H status confers a survival advantage to patients with sporadic CRC.

Aims: To determine if low levels of MSI are related to the clinicopathological features and prognosis of sporadic stage C CRC.

Patients: A total of 255 patients who underwent resection for sporadic stage C CRC were studied. No patient received chemotherapy. Minimum follow up was five years.

Methods: DNA extracted from archival malignant and non-malignant tissue was amplified by polymerase chain reaction using a panel of 11 microsatellites. MSI-H was defined as instability at 40% of markers, MSS as no instability, and MSI-L as instability at >0% but <40% of markers. Patients with MSI-H CRC were excluded from analysis as they have previously been shown to have better survival.

Results: Thirty three MSI-L and 176 MSS CRCs were identified. There was no difference in biological characteristics or overall survival of MSI-L compared with MSS CRC but MSI-L was associated with poorer cancer specific survival (hazard ratio 2.0 (95% confidence interval 1.1–3.6)).

Conclusions: Sporadic MSI-L and MSS CRCs have comparable clinicopathological features. Further studies are required to assess the impact of MSI-L on prognosis.

Abbreviations: CRC, colorectal cancer; MMR, mismatch repair; MSI, microsatellite instability; MSI-H, MSI-high; MSI-L, MSI-low; MSS, microsatellite stable; HNPCC, hereditary non-polyposis colorectal cancer; PCR, polymerase chain reaction

Keywords: microsatellite instability; colorectal cancer; prognosis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Bapat, B., Lindor, N. M., Baron, J., Siegmund, K., Li, L., Zheng, Y., Haile, R., Gallinger, S., Jass, J. R., Young, J. P., Cotterchio, M., Jenkins, M., Grove, J., Casey, G., Thibodeau, S. N., Bishop, D. T., Hopper, J. L., Ahnen, D., Newcomb, P. A., Le Marchand, L., Potter, J. D., Seminara, D., and the Colon Cancer Family Registry, (2009). The Association of Tumor Microsatellite Instability Phenotype with Family History of Colorectal Cancer. Cancer Epidemiol. Biomarkers Prev. 18: 967-975 [Abstract] [Full Text]  
• Asaka, S.-i., Arai, Y., Nishimura, Y., Yamaguchi, K., Ishikubo, T., Yatsuoka, T., Tanaka, Y., Akagi, K. (2009). Microsatellite instability-low colorectal cancer acquires a KRAS mutation during the progression from Dukes' A to Dukes' B. Carcinogenesis 30: 494-499 [Abstract] [Full Text]  
• Haugen, A. C., Goel, A., Yamada, K., Marra, G., Nguyen, T.-P., Nagasaka, T., Kanazawa, S., Koike, J., Kikuchi, Y., Zhong, X., Arita, M., Shibuya, K., Oshimura, M., Hemmi, H., Boland, C. R., Koi, M. (2008). Genetic Instability Caused by Loss of MutS Homologue 3 in Human Colorectal Cancer. Cancer Res. 68: 8465-8472 [Abstract] [Full Text]  
• Xicola, R. M., Llor, X., Pons, E., Castells, A., Alenda, C., Pinol, V., Andreu, M., Castellvi-Bel, S., Paya, A., Jover, R., Bessa, X., Giros, A., Duque, J. M., Nicolas-Perez, D., Garcia, A. M., Rigau, J., Gassull, M. A. (2007). Performance of Different Microsatellite Marker Panels for Detection of Mismatch Repair-Deficient Colorectal Tumors. JNCI J Natl Cancer Inst 99: 244-252 [Abstract] [Full Text]  
• Locker, G. Y., Hamilton, S., Harris, J., Jessup, J. M., Kemeny, N., Macdonald, J. S., Somerfield, M. R., Hayes, D. F., Bast, R. C. Jr (2006). ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer. JCO 24: 5313-5327 [Abstract] [Full Text]  
• Murphy, K. M., Zhang, S., Geiger, T., Hafez, M. J., Bacher, J., Berg, K. D., Eshleman, J. R. (2006). Comparison of the Microsatellite Instability Analysis System and the Bethesda Panel for the Determination of Microsatellite Instability in Colorectal Cancers. J. Mol. Diagn. 8: 305-311 [Abstract] [Full Text]