Pathology Features in Bethesda Guidelines Predict Colorectal Cancer Microsatellite Instability: A Population-Based Study

Jenkins, Mark A.; Hayashi, S.; O’Shea, Anne; Burgart, Lawrence J.; Smyrk, T. C.; Shimizu, David; Waring, Paul; Ruszkiewicz, Andrew; Pollett, Aaron; Redston, Mark; Barker, Melissa; Baron, John A.; Casey, Graham; Dowty, James G.; Giles, Graham G.; Limburg, Paul J.; Newcomb, Polly A.; Young, Joanne; Walsh, Michael D.; Thibodeau, Stephen N.; Lindor, Noralane M.; LeMarchand, Loïc; Gallinger, Steven; Haile, Robert W.; Potter, John D.; Hopper, John L.; Jass, Jeremy R.

doi:10.1053/j.gastro.2007.04.044

Cited by 303 publications

(255 citation statements)

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“…The best score (a score of 0) was attributed to tumors showing marked lymphocytic infiltration and an expanding growth pattern. The Jass grading system was, therefore, heavily influenced by these two variables which have been subsequently found to be typical characteristics of MSI colorectal adenocarcinoma [26]. That is, our proposed criteria for integrating MSI status with the histologic grading of colorectal adenocarcinoma can be seen as a simplified version of the Jass grading system.…”

Section: Discussionmentioning

confidence: 96%

Should the grading of colorectal adenocarcinoma include microsatellite instability status?

et al. 2014

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Adenocarcinomas of the colon and rectum are graded using a two-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 lowgrade tumors (20% vs. 6%; P<0.001). Using Cox regression models, adjusting for sex, age at diagnosis and stratifying by the American Joint Committee on Cancer (AJCC) stage, microsatellite stable (MSS) high-grade tumors were associated with increased hazard of allcause and colorectal cancer-specific mortality: hazard ratio (HR) 2.09 (95% confidence interval (CI), 1.58-2.77) and 2.54 (95% CI, 1.86-3.47), respectively, both P<0.001. 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.

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Section: Discussionmentioning

confidence: 96%

Should the grading of colorectal adenocarcinoma include microsatellite instability status?

et al. 2014

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“…[24][25][26][27][28][29][30][31][32] Jenkins et al 39 recently proposed a score to predict microsatellite instability high colorectal cancer based on characteristic features associated with this subgroup of tumors including age at diagnosis, anatomical site, histologic subtype, tumor grade, Crohn-like reaction and intratumoral lymphocytes. The immunohistochemical phenotype of microsatellite instability high colorectal cancer is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status

et al. 2008

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The differentiation of colorectal cancer from primary tumors at other sites can be challenging. Often a panel of immunohistochemical protein markers is needed to distinguish between these entities. Protein expression differs significantly in colorectal cancer depending on mismatch repair status and is also heterogeneous among mismatch repair-proficient or -deficient tumors. The aim of this study was to systematically analyze the diagnostic and prognostic role of the commonly used multi-marker phenotype CK20/CK7/CDX2 on a large series of colorectal cancers stratified by mismatch repair status. The immunohistochemical analysis of CK20, CK7 and CDX2 was performed on 1197 mismatch repair-proficient and 223 mismatch repair-deficient colorectal cancers using a tissue microarray. Multi-marker combinations of CK20/CK7/CDX2 were explored. Univariate and multivariable analysis of the markers was evaluated for their association with several clinico-pathological end points namely T stage, N stage, tumor grade, vascular invasion, intratumoral lymphocytes and survival. Multimarker phenotypes with CK20 and CDX2 negativity were more frequently found in mismatch repair-deficient than in mismatch repair-proficient colorectal cancer (19.3 vs 7.5% and 21.6 vs 6.7%, respectively; Po0.001). In both colorectal cancer subsets loss of CK20 was associated with higher tumor grade (Po0.001) and with presence of intratumoral lymphocytes (Po0.001 and P ¼ 0.02, respectively). In the proficient mismatch repair subset CK20 overexpression was an independent adverse prognostic factor (P ¼ 0.041) and CDX2 underexpression was linked to tumor progression. Loss of CDX2 and CK20 is more frequently encountered in mismatch repair-deficient colorectal cancer, which should be taken into consideration to differentiate between primary and metastatic colorectal cancer in daily practice. Although associated with lower tumor grade, CK20 overexpression is an independent adverse prognostic factor in mismatch repair-proficient colorectal cancer.

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“…Conversely, MSI is rarely found in sporadic adenomas, so a positive finding in an adenoma is very suggestive of Lynch syndrome (Stoffel and Syngal, 2005). An accelerated development from adenoma to colorectal cancer also occurs in adenomas with MSI (Geiersbach and Samowitz, 2011;Jenkins et al, 2007). This may explain the frequent interval CRCs that occur in Lynch kindreds despite colonoscopic surveillance .…”

Section: Colorectal Adenomas With Msimentioning

confidence: 98%

“…MSI CRC is most frequently found in the right colon, is associated with; poorly differentiated tumours, a high mucinous component, numerous tumor-infiltrating lymphocytes (TILs), and with the presence of a "Crohn's-like" host response (Jenkins et al, 2007;Wright and Stewart, 2003). Despite the association of MSI with more advance grade it appears that grade is not associated with prognosis in dMMR (Mohan et al, 2016;Rosty et al, 2014;Ward et al, 2001).…”

Section: Phenotypic Differences Between Msi and Mss Colorectal Cancermentioning

confidence: 99%

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

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Pathology Features in Bethesda Guidelines Predict Colorectal Cancer Microsatellite Instability: A Population-Based Study

Abstract: Background & Aims-The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology

Cited by 303 publications

References 50 publications

Should the grading of colorectal adenocarcinoma include microsatellite instability status?

Should the grading of colorectal adenocarcinoma include microsatellite instability status?

Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

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