Low-Level Microsatellite Instability as a Potential Prognostic Factor in Sporadic Colorectal Cancer

p63 is highly expressed in some malignant tumors and is associated with tumorigenesis, invasion and metastasis. The aim of our study was to evaluate the clinical significance of p63 in colorectal cancer (CRC). p63 expression was detected by immunohistochemistry in 66 CRC patients. Correlations between p63 expression and clinicopathological factors, progression-free survival (PFS) and overall survival (OS) were analyzed. Among the 66 CRC cases, 31 cases (47%) exhibited a high score of p63 expression, while 35 cases (53%) were marked with a low score. The p63 level correlated with peritumoral deposits (p=0.021). The 5-year OS rates in the low p63 score and high p63 score groups were, respectively, 49% and 74% (p<0.001). The 5-year PFS rates in the low p63 score and high p63 score groups were, respectively, 44% and 71% (p<0.001). Univariate analysis revealed that p63 expression was correlated with OS and PFS. Multivariate analysis suggested that p63 expression was an independent prognostic factor for OS (p=0.035). In conclusion, p63 was negatively correlated with peritumoral deposits and positively associated with OS and PFS in CRC. The data suggest that p63 is a potential prognostic factor for CRC.

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Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-006-0147-z ◽

2006 ◽

Vol 133 (1) ◽

pp. 65-70 ◽

Cited By ~ 6

Author(s):

P. Chaksangchaichot ◽

P. Punyarit ◽

S. Petmitr

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Gene Mutations ◽

Sporadic Colorectal Cancer ◽

Hmlh1 Gene

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Methylation in p14ARF is Frequently Observed in Colorectal Cancer with Low-level Microsatellite Instability

Journal of International Medical Research ◽

10.1177/147323000903700408 ◽

2009 ◽

Vol 37 (4) ◽

pp. 1038-1045 ◽

Cited By ~ 8

Author(s):

K Kominami ◽

T Nagasaka ◽

HM Cullings ◽

N Hoshizima ◽

H Sasamoto ◽

...

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Promoter Methylation ◽

Dna Methyltransferase ◽

Methylation Status ◽

Gene Promoters ◽

Braf Mutations ◽

Low Level ◽

Methylguanine Dna Methyltransferase ◽

High Level

Colorectal cancer (CRC) can be classified as high-level microsatellite instability (MSI-H), low-level MSI (MSI-L) and microsatellite stable (MSS) depending on levels of MSI. MSI-H CRC relies on a distinct molecular pathway due to the mismatch repair (MMR) deficiency and shows methylation in multiple gene promoters. The genetic pathway leading to MSI-L is unknown, although higher levels of promoter methylation are observed in this group compared with MSS CRCs. This study explored how promoter methylation affects MSI phenotype, by analysing the methylation status of eight CRC-related promoters, MSI phenotype and KRAS/BRAF mutations in a series of 234 CRCs. Promoter methylation of p14ARF was significantly related to MSI-L CRC with KRAS mutation. The MSI-H phenotype was related to methylation of MLH1 as expected, while the MSS phenotype was related to methylation of p16INK4a and O6-methylguanine-DNA methyltransferase, although this was not statistically significant. Thus, promoter methylation of p14ARF could be a significant alteration leading to CRC with MSI-L.

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Adenoma incidence after resection of sporadic colorectal cancer with microsatellite instability

Journal of Surgical Oncology ◽

10.1002/jso.21548 ◽

2010 ◽

Vol 101 (7) ◽

pp. 577-581 ◽

Cited By ~ 5

Author(s):

Ki Joo Kang ◽

Dong Hyun Sinn ◽

Sung Hyun Park ◽

Jin Yong Kim ◽

Dong Kyung Chang ◽

...

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Sporadic Colorectal Cancer

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Use of immunohistochemical versus microsatellite analyses as markers for colorectal cancer

Turkish Journal of Biochemistry ◽

10.1515/tjb-2017-0050 ◽

2017 ◽

Vol 43 (2) ◽

pp. 134-141

Author(s):

Utku Tantoğlu ◽

Seher Yüksel ◽

Cihangir Akyol ◽

Haldun Doğan ◽

Nükhet Kutlay ◽

...

Keyword(s):

Colorectal Cancer ◽

Lynch Syndrome ◽

Microsatellite Instability ◽

Mismatch Repair ◽

Immunohistochemical Analysis ◽

Sporadic Colorectal Cancer ◽

Molecular Tests ◽

Antibody Panel ◽

Mismatch Repair Proteins ◽

Good Concordance

Abstract Objectives: Our aim was to determine how well immunohistochemical analysis identified colon cancer patients with microsatellite instability in Turkish patients. Material and methods: Subjects were patients that underwent surgery for colorectal cancer in our institution between 2006 and 2011. Patients were grouped as: (1) suspected Lynch syndrome (n=14), (2) familial colorectal cancer (n=14), and (3) sporadic colorectal cancer groups (n=14). Mismatch repair proteins were analyzed by a four antibody-panel immunohistochemistry. Microsatellite instability analysis was conducted on DNA samples using MSI-PCR followed by fragment analysis. Results: The immunohistochemistry and PCR results had good concordance in 35/42 patients. Both microsatellite instability and at least one mismatch repair protein deficiency were detected in 11 patients, and both microsatellite stability and normal expression of mismatch repair proteins were detected in 24 patients. Test results were discordant in seven of the patients. Conclusion: As it is not feasible to perform expensive molecular tests in healthcare units in many developing countries, the four antibody-panel immunohistochemistry is a reliable and affordable method for screening for colorectal cancer, including Lynch syndrome and sporadic cases when suspected.

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Clinical Significance and Prognostic Relevance of Microsatellite Instability in Sporadic Colorectal Cancer Patients

International Journal of Molecular Sciences ◽

10.3390/ijms18010107 ◽

2017 ◽

Vol 18 (1) ◽

pp. 107 ◽

Cited By ~ 31

Author(s):

Angelika Copija ◽

Dariusz Waniczek ◽

Andrzej Witkoś ◽

Katarzyna Walkiewicz ◽

Ewa Nowakowska-Zajdel

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Cancer Patients ◽

Clinical Significance ◽

Sporadic Colorectal Cancer ◽

Prognostic Relevance ◽

Colorectal Cancer Patients

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Quasimonomorphic Mononucleotide Repeats for High-Level Microsatellite Instability Analysis

Disease Markers ◽

10.1155/2004/159347 ◽

2004 ◽

Vol 20 (4-5) ◽

pp. 251-257 ◽

Cited By ~ 89

Author(s):

Olivier Buhard ◽

Nirosha Suraweera ◽

Aude Lectard ◽

Alex Duval ◽

Richard Hamelin

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Screening Test ◽

Consensus Meeting ◽

Dinucleotide Repeats ◽

Primary Tumors ◽

Low Level ◽

High Level ◽

Msi Analysis ◽

Microsatellite Instability Analysis

Microsatellite instability (MSI) analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats) to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability.

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