Clinicopathological significance of microsatellite instability and mutated RIZ in colorectal cancer.
BACKGROUND
Several studies have shown that microsatellite instability (MSI) is related to favourable survival in colorectal cancer patients but there are controversial results. Tumour suppressor gene RIZ is a susceptible mutational target of MSI. However, its clinicopathological significance has not been investigated. We investigated the prognostic significance of MSI in Swedish colorectal cancer patients and the clinicopathological significance of RIZ mutations.


METHODS
We analysed 438 colorectal adenocarcinomas for MSI by microsatellite analysis. Among them, 29 MSI and 28 microsatellite stable (MSS) tumours were examined for RIZ mutations by DNA sequencing.


RESULTS
MSI (13% of 438 cases) was not associated with survival (rate ratio = 0.97, 95% confidence interval = 0.57-1.64, P = 0.90), although it was related to proximal tumour (P <0.001), poor differentiation and mucinous carcinomas (P <0.001), multiple tumours (P = 0.01) and negative/weak expression of hMLH1 (P = 0.03). RIZ mutations were detected in 31% of 29 MSI tumours but in none of the 28 MSS tumours. The mutations were related to female (P = 0.01), proximal tumour (P = 0.01), stage B (P = 0.01) and poor differentiation (P = 0.047).


CONCLUSIONS
MSI was not a prognostic factor in the Swedish patients included in this study. Clinicopathological variables associated with RIZ mutations might be a consequence of the MSI characteristics.
Emterling
A
A
Department of Oncology, Linköping University, Linköping, Sweden.
Wallin
A
A
Arbman
G
G
Sun
X-F
XF
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human