Low Microsatellite Instability Is Associated With Poor Prognosis in Stage C Colon Cancer

Kohonen‐Corish, Maija; Daniel, Joseph J.; Chan, Charles; Lin, Betty; Kwun, Sun Young; Dent, Owen F.; Dhillon, Varinderpal S.; Trent, Ronald J.; Chapuis, Pierre; Bokey, E. L.

doi:10.1200/jco.2005.00.109

Cited by 108 publications

(90 citation statements)

References 24 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: Discussionmentioning

confidence: 62%

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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: Discussionmentioning

confidence: 62%

“…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%

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

et al. 2006

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“…These were previously examined for microsatellite instability, CDKN2A methylation, MGMT and mismatch repair protein expression (Kohonen-Corish et al, 2005). Frozen biopsies of tumor and matching normal tissue were available for protein analysis from an additional 10 cancers from eight patients.…”

Section: Methodsmentioning

confidence: 99%

“…PCR conditions were 951C (30 s), 611C (45 s) and 721C (30 s) for 35 cycles. CDKN2A promoter methylation was analysed as previously described (Herman et al, 1996;Kohonen-Corish et al, 2005). The MYOD1 primers, which do not contain any CpG nucleotide sequences, were used as an internal reference PCR to ensure integrity of each DNA specimen (Eads et al, 1999(Eads et al, , 2000.…”

Section: Methylation-specific Pcrmentioning

confidence: 99%

Promoter methylation of the mutated in colorectal cancer gene is a frequent early event in colorectal cancer

et al. 2007

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“…Reduced MLH1 expression was taken for a score less than 100, of the maximum score of 300. MSI was analysed as previously described (Kohonen-Corish et al, 2005, except that only two markers BAT25 and BAT26 were evaluated, which are sufficient for detecting high MSI (Suraweera et al, 2002).…”

Section: Immunohistochemistry and Msi Analysismentioning

confidence: 99%

DLEC1 and MLH1 promoter methylation are associated with poor prognosis in non-small cell lung carcinoma

et al. 2008

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The significance of chromosome 3p gene alterations in lung cancer is poorly understood. This study set out to investigate promoter methylation in the deleted in lung and oesophageal cancer 1 (DLEC1), MLH1 and other 3p genes in 239 non-small cell lung carcinomas (NSCLC). DLEC1 was methylated in 38.7%, MLH1 in 35.7%, RARb in 51.7%, RASSF1A in 32.4% and BLU in 35.3% of tumours. Any two of the gene alterations were associated with each other except RARb. DLEC1 methylation was an independent marker of poor survival in the whole cohort (P ¼ 0.025) and in squamous cell carcinoma (P ¼ 0.041). MLH1 methylation was also prognostic, particularly in large cell cancer (P ¼ 0.006). Concordant methylation of DLEC1/MLH1 was the strongest independent indicator of poor prognosis in the whole cohort (P ¼ 0.009). However, microsatellite instability and loss of MLH1 expression was rare, suggesting that MLH1 promoter methylation does not usually lead to gene silencing in lung cancer. This is the first study describing the prognostic value of DLEC1 and MLH1 methylation in NSCLC. The concordant methylation is possibly a consequence of a long-range epigenetic effect in this region of chromosome 3p, which has recently been described in other cancers.

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Low Microsatellite Instability Is Associated With Poor Prognosis in Stage C Colon Cancer

Abstract: MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.

Cited by 108 publications

References 24 publications

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

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

Promoter methylation of the mutated in colorectal cancer gene is a frequent early event in colorectal cancer

DLEC1 and MLH1 promoter methylation are associated with poor prognosis in non-small cell lung carcinoma

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