Should the grading of colorectal adenocarcinoma include microsatellite instability status?

Rosty, Christophe, Williamson, Elizabeth J., Clendenning, Mark, Walters, Rhiannon J., Win, Aung K., Jenkins, Mark A., Hopper, John L., Winship, Ingrid M., Southey, Melissa C., Giles, Graham G., English, Dallas R. and Buchanan, Daniel D. (2014) Should the grading of colorectal adenocarcinoma include microsatellite instability status?. Human Pathology, 45 10: 2077-2084. doi:10.1016/j.humpath.2014.06.020

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Author Rosty, Christophe
Williamson, Elizabeth J.
Clendenning, Mark
Walters, Rhiannon J.
Win, Aung K.
Jenkins, Mark A.
Hopper, John L.
Winship, Ingrid M.
Southey, Melissa C.
Giles, Graham G.
English, Dallas R.
Buchanan, Daniel D.
Title Should the grading of colorectal adenocarcinoma include microsatellite instability status?
Journal name Human Pathology   Check publisher's open access policy
ISSN 0046-8177
Publication date 2014-10
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.humpath.2014.06.020
Open Access Status
Volume 45
Issue 10
Start page 2077
End page 2084
Total pages 8
Place of publication Maryland Heights, MO, United States
Publisher W.B. Saunders
Collection year 2015
Language eng
Formatted abstract
Adenocarcinomas of the colon and rectum are graded using a 2-tiered system into histologic low-grade and high-grade tumors based on the proportion of gland formation. The current grading system does not apply to subtypes of carcinomas associated with a high frequency of microsatellite instability (MSI), such as mucinous and medullary carcinomas. We investigated the combined effect of histologic grade and MSI status on survival for 738 patients with colorectal carcinoma (48% female; mean age at diagnosis 68.2 years). The proportion of high-grade adenocarcinoma was 18%. MSI was observed in 59 adenocarcinomas (9%), with higher frequency in high-grade tumors compared with low-grade tumors (20% versus 6%; P < .001). Using Cox regression models, adjusting for sex and age at diagnosis and stratifying by the American Joint Committee on Cancer stage, microsatellite stable (MSS) high-grade tumors were associated with increased hazard of all-cause and colorectal cancer-specific mortality: hazard ratio 2.09 (95% confidence interval [CI], 1.58-2.77) and 2.54 (95% CI, 1.86-3.47), respectively, both P < .001. A new grading system separating adenocarcinoma into low grade (all histologic low grade and MSI high grade) and high grade (MSS histologic high grade) gave a lower Akaike information criterion value when compared with the current grading system and thus represented a better model fit to stratify patients according to survival. We found that patients with a high-grade adenocarcinoma had significantly shorter survival than patients with low-grade adenocarcinoma only if the tumor was MSS, suggesting that the grading of colorectal adenocarcinoma with high-grade histologic features should be made according to the MSI status of the tumor.
Keyword Colorectal cancer
Microsatellite instability
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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