Microsatellite instability in sporadic colorectal cancer is not an independent prognostic factor

Salahshor, Sima; Kressner, Ulf; Fischer, Håkan; Lindmark, Gunilla; Glimelius, Bengt; Påhlman, Lars; Lindblom, Annika

doi:10.1038/sj.bjc.6690676

Cited by 97 publications

(59 citation statements)

References 17 publications

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“…In general, cases of CRLM appear to maintain relatively low MSI rates when compared with corresponding primary tumours, which consistently maintain MSI rates of 15-20%. This difference has been indicated to be statistically significant in at least one matched study (10). The absence of data regarding the MSI status of primary tumours in the present study precludes a discussion regarding corresponding expression.…”

Section: Discussionmentioning

confidence: 49%

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The incidence of mismatch repair gene defects in colorectal liver metastases

Alvarado-Bachmann

Smith

Gundara

et al. 2014

Molecular Medicine Reports

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Abstract. Knowledge of the molecular biology of primary colorectal cancer (CRC) has improved in recent years, and one reason for this is the identification of microsatellite instability (MSI), which occurs in up to 15% of sporadic CRC. However, less is known regarding the processes involved in colorectal liver metastases (CRLM). Increasing numbers of patients with CRLM are suitable for curative resection, so the identification of molecular markers may improve patient selection. The aim of the present study was to characterise the incidence of MSI in resected CRLM. Fifty-one sequentially resected CRLM specimens were selected. Clinicopathologic data was collated and immunohistochemistry for MLH1 and MSH2 was performed on paraffin sections of the CRLM specimens. The association between abnormal staining and the clinicopathological data was examined. The median age of the subjects in the current study was 65 years, the average number of CRLM was 2 and the median overall survival time was 42.1 months post liver resection. None of the 50 resected specimens demonstrated abnormal staining for MLH1 or MSH2. Compared with the previously reported incidence of MSI in primary CRC, the low incidence of MSI in the current cohort of CRLM precludes its use as a marker for use in making clinical decisions regarding this condition.

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Section: Discussionmentioning

confidence: 49%

“…These parameters have significant limitations and are based on population data rather than being individualized for each patient. Recent attention has therefore focused on the relevance of molecular prognostic markers (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

The incidence of mismatch repair gene defects in colorectal liver metastases

Alvarado-Bachmann

Smith

Gundara

et al. 2014

Molecular Medicine Reports

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“…Data on the prognosis of MSI-H CRC are conflicting. Salahshor et al (1999) found an obvious trend towards a better outcome of their MSI-H collective, but this was not statistically significant. Feeley et al (1999) could not see any impact of microsatellite status on patients' survival at all, but the validity of this study is limited by the low number of MSI-H cases.…”

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confidence: 73%

Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases

et al. 2005

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Colorectal carcinomas (CRCs) with high microsatellite instability (MSI-H) share clinicopathological features distinctly different from their microsatellite stable (MSS) counterparts. Unlike MSS cancers, MSI-H CRCs occur predominantly in the right-sided colon and are often characterised by a strong lymphocyte infiltration. A poor differentiation pattern is found in most MSI-H CRCs, even though patients with MSI-H carcinomas seem to have a significantly longer survival after surgical resection. To clarify which factors contribute to the obvious paradoxon of a more favourable prognosis of MSI tumours, several clinical and histopathological features as well as the microsatellite status were evaluated in 120 colorectal cancer cases fulfilling clinical criteria (Bethesda) indicative for familial colorectal cancer. Microsatellite instablity status and lymphocyte infiltration were related to tumour stage and patients' follow-up. Statistical analysis confirmed well-known relations, such as enhanced lymphocyte infiltration accompanied by Crohn's like reaction (CLR) in MSI-H cancers (CLR þ in 27 out of 47 MSI-H vs 14 out of 71 MSS CRCs, Po0.001). However, after stratification for depth of local invasion and penetration of the primary tumour, T3 tumours displaying MSI had a significantly lower rate of distant metastases (M1 in four out of 35 MSI-H vs 20 out of 41 MSS CRCs, Po0.001). A similar tendency was observed for CLR-positive CRCs (M1 in six out of 29 CLR þ vs 17 out of 45 CLRÀ CRCs, P ¼ 0.13). In a logistic regression model, the MSI-H phenotype and the presence of CLR were independent predictors of a low UICC stage (P ¼ 0.006 and 0.04, respectively). These data, together with the recent definition of highly immunogenic neo-antigens expressed in MSI-H tumour cells, suggest that MSI-H CRCs elicit a protective host response that may prevent metastasis formation.

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“…Several studies have found no correlation between MSI and age in patients with colon carcinoma. 17,[27][28][29][30] However, most of those studies had a small sample sizes and may have lacked the power to detect statistically significant associations. hMLH1 expression loss spread over different age groups was not examined systematically in any of those studies.…”

Section: Hmlh1 Expression Loss Age and Gendermentioning

confidence: 99%

Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age

Kakar

Burgart

Thibodeau

et al. 2003

Cancer

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BACKGROUNDThe correlation between age at diagnosis and loss of expression of hMLH1 protein in patients with colorectal carcinoma (CRC) has not been evaluated systematically.METHODSImmunohistochemistry was performed for hMLH1 protein in tumor samples from 867 patients with CRC. The authors defined tumors arising in the cecum, ascending colon, and transverse colon as right‐sided and tumors arising in the descending colon, sigmoid colon, and rectum as left‐sided. Patients' gender, tumor location (side), and hMLH1 expression were analyzed by age groups.RESULTSThe percentage of tumors with hMLH1 expression loss increased significantly with advancing age (P < 0.0001): There were no tumors in patients age < 40 years that manifested loss of hMLH1 expression, compared with 29% of tumors that manifested loss of hMLH1 expression in patients age > 90 years. Loss of hMLH1 expression occurred more often in patients with right‐sided tumors (32.7% vs. 5.2% of patients with left‐sided tumors; P < 0.0001) and in tumors from female patients (24.3% vs. 11.5% of tumors from male patients; P < 0.0001). There was no evidence of interaction between gender and tumor location.CONCLUSIONSLoss of hMLH1 expression in patients with CRC was associated strongly with increasing age. hMLH1 expression loss was more pronounced in tumors from female patients and in tumors that originated on the right side of the colon. Loss of hMLH1 expression in right‐sided tumors occurred in nearly 50% of patients age > 90 years. This age‐related trend also was observed for males and in tumors that originated in the left colon. Cancer 2003;97:1421–7. © 2003 American Cancer Society.DOI 10.1002/cncr.11206

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Microsatellite instability in sporadic colorectal cancer is not an independent prognostic factor

Cited by 97 publications

References 17 publications

The incidence of mismatch repair gene defects in colorectal liver metastases

The incidence of mismatch repair gene defects in colorectal liver metastases

Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases

Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age

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