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 and 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

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