Low level microsatellite instability may be associated with reduced cancer specific survival in sporadic stage C colorectal carcinoma

Wright, Caroline; Dent, O. F.; Newland, R. C.; Barker, Melissa; Chapuis, P. H.; Bokey, E. L.; Young, Joanne; Leggett, Barbara A.; Jass, Jeremy R.; Macdonald, Graeme A.

doi:10.1136/gut.2003.034579

Cited by 62 publications

(54 citation statements)

References 30 publications

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“…Additionally, MSI low tumors show a lower antitumor immune response (lack of intraepithelial, peritumoral and intertumoral lymphocytes and Crohn's-like lymphoid reaction), a known marker for worse prognosis. 15,16 These data may explain the worse prognosis of MSI low tumors that was shown in the studies of Kohonen-Corish et al 7 and Wright et al 8 Data on survival are not available in our study. In contrast to previous studies on sporadic tumors, 8,17,18 we found differences in clinicopathological features between MSI low and MSS tumors.…”

Section: Discussioncontrasting

confidence: 49%

“…15,16 These data may explain the worse prognosis of MSI low tumors that was shown in the studies of Kohonen-Corish et al 7 and Wright et al 8 Data on survival are not available in our study. In contrast to previous studies on sporadic tumors, 8,17,18 we found differences in clinicopathological features between MSI low and MSS tumors. This may be explained by the fact that we focused on familial CRCs, which might generate groups with more homogeneous etiologies.…”

Section: Discussioncontrasting

confidence: 49%

“…6 Moreover, MSI low tumors may confer a worse prognosis. 7,8 Little is known about the histopathological features of familial MSI low tumors. To clarify the importance of MSI low status in colorectal tumors of patients suspected of HNPCC, tumors were classified as MSI low or MSS according to strict criteria.…”

Section: Hereditarymentioning

confidence: 99%

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Unfavorable pathological characteristics in familial colorectal cancer with low-level microsatellite instability

et al. 2006

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A high degree of microsatellite instability (MSI) in colorectal cancer (CRC) is a hallmark of hereditary nonpolyposis colorectal cancer (HNPCC), caused by germline defects in the mismatch repair (MMR) genes. A low degree of instability (less than 30% of the microsatellites) is seen in a subset of tumors. To clarify the significance of this low degree of MSI phenotype, we studied the differences between patients with colorectal tumors with high-level, low-level and no MSI. Colorectal tumors with no (n ¼ 68) and low-level (n ¼ 18) MSI of patients clinically suspected of HNPCC were compared to colorectal tumors with high-level MSI (n ¼ 12) of patients that carry a pathogenic germline mutation in a MMR gene. Compared to tumors with no MSI, tumors with low-level MSI were classified more frequently as stage T3 or T4 (100% vs 68% respectively), and showed less immune response (P ¼ 0.02). No significant differences in familial CRC risk were found by comparing pedigrees of these two groups of tumors. Compared to the group of tumors with high-level MSI, the group of tumors with low-level MSI had a less suspicious family history, a higher percentage of lymph node metastasis (56 vs 17%), and less immune response. Thus, with respect to genetic risks, familial CRC can be divided into two groups: Tumors with high-level MSI and tumors with low-level or no MSI. However, tumors with low-level MSI show unfavorable pathological characteristics compared to tumors with no and tumors with high-level MSI. These differences suggest a distinct underlying biology of CRC with low-level MSI.

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Section: Discussioncontrasting

confidence: 49%

Section: Discussioncontrasting

confidence: 49%

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Unfavorable pathological characteristics in familial colorectal cancer with low-level microsatellite instability

et al. 2006

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“…33 MSI also has demonstrated prognostic value in very young CRC patient populations 34 and, in several heterogeneous (stage-dependent) analyses, included patients of all ages derived from trials on adjuvant chemotherapy or selected cohorts of patients. 14,15,17,18,28,32,35,36 In the current population-based study on surveillance after surgery, the exclusion of elderly patients may have masked an overall survival benefit with regard to MSI. However, the current results are in line with several other studies, which reported no statistically significant difference in DSS for patients who had MSI tumors, although the results demonstrated nonsignificant trends or only stage-dependent improved overall survival for patients who had MSI tumors.…”

Section: Discussionmentioning

confidence: 99%

Microsatellite instability and DNA ploidy in colorectal cancer

Søreide

Slewa

Stokkeland

et al. 2009

Cancer

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BACKGROUND:Appropriate stratification tools for targeted surveillance after resection for colorectal cancer (CRC) are lacking. The objective of the current study was to investigate the effect of microsatellite instability (MSI) and DNA ploidy on surveillance after surgery.METHODS:The authors evaluated 186 consecutive, population‐based patients with stage I through III CRC who underwent surgery with curative intent and who entered a systematic surveillance program. MSI was analyzed with polymerase chain reaction for 5 known quasimonomorphic markers (BAT‐26, BAT‐25, NR‐21, NR‐24, and NR‐27), and DNA ploidy was analyzed with automated cytometry. Recurrence, recurrence‐free survival (RFS), and disease‐specific survival (DSS) were evaluated by univariate and multivariate statistical tests.RESULTS:Patients with MSI (20%) were significantly younger than patients without MSI (median age, 61 years vs 67 years; P = .016). Proximal location (adjusted odds ratio [AOR], 5.4; 95% confidence interval [95% CI], 2.1‐14.1 [P = .001]), large tumor size (≥5 cm: AOR, 3.5; 95% CI, 1.3–9.6 [P = .015]), and poor tumor differentiation (AOR, 6.6; 95% CI, 2–21.8 [P = .002]) were associated with MSI. MSI conveyed an increased risk for locoregional recurrence (OR, 2.9; 95% CI, 1.2–7 [P = .016]), with a trend toward a shorter time to recurrence (P = .060). Neither MSI status nor DNA ploidy predicted distant metastasis, RFS, or DSS. Lymph node status was the best predictor of distant spread (AOR, 3.9; 95% CI, 2–7.9 [P < .001]) and DSS (hazard ratio, 4.9; 95% CI, 2.6–9 [P < .001]).CONCLUSIONS:Patients who had microsatellite instable tumors were at increased risk for locoregional recurrence, whereas lymph node status was the best predictor of distant metastasis. Clinical surveillance and choice of modality (ie, endoscopy vs radiologic imaging) may be improved when patients are stratified according to these cancer features. Cancer 2009. © 2009 American Cancer Society.

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“…Interestingly, the DNA repair gene O-6-methylguanine DNA methyltransferase (MGMT) is epigenetically silenced more frequently in MSI-L tumours than in both MSI-H and MSS cancers 77 , which suggests a different method of DNA error repair. MSI-L status has been related to poor prognosis in patients with stage C cancers 12 . Although techniques for improved detection of these subtle differences are developing, such as hypermethylation of MGMT 78 , the true clinicopathological yield of MSI-L status remains to be established.…”

Section: Microsatellite Frequencymentioning

confidence: 99%