Genomic instability and tissue expression of angiogenic growth factors in sporadic colorectal cancer

Inoue, Yasuhiro; Miki, Chikao; Watanabe, Hideki; Ojima, Eiki; Kusunoki, Masato

doi:10.1016/j.surg.2005.08.006

Cited by 10 publications

(11 citation statements)

References 32 publications

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“…Moreover, MSI-positive CRC seem to show a reduced microvessel density, due to a lower vascular endothelial growth factor (VEGF) levels [ 19 – 21 ] and, consequently, a reduced metastatic potential. Another explanation could be that MMR defects can affect the viability of tumour cells through the accumulation of mutations in genes necessary for cancer cell survival.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of mismatch repair genes germline defects in colorectal cancer patients: are all mutations equal?

et al. 2015

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BackgroundLynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline mutations in MisMatch Repair (MMR) genes, particularly in MLH1, MSH2 and MSH6. Patients with LS seem to have a more favourable prognosis than those with sporadic CRC, although the prognostic impact of different mutation types is unknown.Aim of our study is to compare survival outcomes of different types of MMR mutations in patients with LS-related CRC.Methods302 CRC patients were prospectively selected on the basis of Amsterdam or Revised Bethesda criteria to undergo genetic testing: direct sequencing of DNA and MLPA were used to examine the entire MLH1, MSH2 and MSH6 coding sequence.Patients were classified as mutation-positive or negative according to the genetic testing result.ResultsA deleterious MMR mutation was found in 38/302 patients. Median overall survival (OS) was significantly higher in mutation-positive vs mutation-negative patients (102.6 vs 77.7 months, HR:0.63, 95%CI:0.46–0.89, p = 0.0083). Different types of mutation were significantly related with OS: missense or splicing-site mutations were associated with better OS compared with rearrangement, frameshift or non-sense mutations (132.5 vs 82.5 months, HR:0.46, 95%CI:0.16–0.82, p = 0.0153).ConclusionsOur study confirms improved OS for LS-patients compared with mutation-negative CRC patients. In addition, not all mutations could be considered equal: the better prognosis in CRC patients with MMR pathogenic missense or splicing site mutation could be due to different functional activity of the encoded MMR protein. This matter should be investigated by use of functional assays in the future.

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Section: Discussionmentioning

confidence: 99%

Prognostic impact of mismatch repair genes germline defects in colorectal cancer patients: are all mutations equal?

et al. 2015

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“…Research has been focused on the development of cancer and its progression, by studying epigenetics and tumor suppressor genes. It was reported that microsatellite instability (MSI) and loss of heterozygosity (LOH) are associated with gastric cancer [1][2][3][4][5] . In addition, gene promoter region hypermethylation can activate certain tumor suppressor genes.…”

Section: Introductionmentioning

confidence: 99%

Role ofBMP3in progression of gastric carcinoma in Chinese people

Chen

Wang²,

Li³

et al. 2010

WJG

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“…However, since it is the biomarker potential of the MSI status that should be tested in future studies, this concern is of less importance. The clinical implications 10 000 1000 100 10 Test cohort MSS MSI MSS MSI Validation cohort sVEGF-A pg/ml Figure 1 Dot plot illustrating the distribution of serum vascular endothelial growth factor A in the test and validation cohorts according to microsatellite instability status. The differences between the medians were significant (0.01 in the test cohort and P = 0.04 in the validation cohort).…”

Section: Discussionmentioning

confidence: 99%

The relationship between serum vascular endothelial growth factor A and microsatellite instability in colorectal cancer

Hansen¹,

Jensen²,

Spindler³

et al. 2010

Colorectal Disease

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Genomic instability and tissue expression of angiogenic growth factors in sporadic colorectal cancer

Cited by 10 publications

References 32 publications

Prognostic impact of mismatch repair genes germline defects in colorectal cancer patients: are all mutations equal?

Prognostic impact of mismatch repair genes germline defects in colorectal cancer patients: are all mutations equal?

Role ofBMP3in progression of gastric carcinoma in Chinese people

The relationship between serum vascular endothelial growth factor A and microsatellite instability in colorectal cancer

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