EMAST Is Associated with a Poor Prognosis in Microsatellite Instable Metastatic Colorectal Cancer

被引:23
|
作者
Venderbosch, Sabine [1 ,3 ]
van Lent-van Vliet, Shannon [1 ]
de Haan, Anton F. J. [2 ]
Ligtenberg, Marjolijn J. [1 ,4 ]
Goossens, Monique [1 ]
Punt, Cornelis J. A. [3 ]
Koopman, Miriam [5 ]
Nagtegaal, Iris D. [1 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6500 HB Nijmegen, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Dept Med Oncol, NL-1100 DD Amsterdam, Netherlands
[4] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands
[5] Univ Med Ctr Utrecht, Dept Med Oncol, NL-3508 GA Utrecht, Netherlands
来源
PLOS ONE | 2015年 / 10卷 / 04期
关键词
TETRANUCLEOTIDE REPEATS; COLON-CANCER; MUTATOR PHENOTYPE; HMLH1; PROMOTER; INSTABILITY; REPAIR; MUTATIONS; CARCINOMA; CELLS; HMSH6;
D O I
10.1371/journal.pone.0124538
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Purpose To determine the frequency and prognostic value of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in metastatic colorectal cancer (mCRC) patients in relation to microsatellite instability (MSI) status and MSH3 protein expression. Material and Methods The frequency of EMAST was evaluated in mCRC patients with MSI tumors and microsatellite stable (MSS) tumors. A literature overview was performed to compare the frequency of EMAST in our study with existing data. Immunohistochemistry for MSH3 was compared with EMAST status. Outcome was studied in terms of overall survival (OS) of mCRC patients with MSI and MSS tumors. Results EMAST was evaluated in 89 patients with MSI tumors (including 39 patients with Lynch syndrome) and 94 patients with MSS tumors. EMAST was observed in 45.9% (84 out of 183) of patients, with an increased frequency in MSI tumors (79.8% versus 13.8%, p < 0.001). We found no correlation between EMAST and MSH3 protein expression. There was no effect of EMAST on prognosis in patients with MSS tumors, but patients with MSI/non-EMAST tumors had a significantly better prognosis than patients with MSI/EMAST tumors (OS: HR 3.22, 95% CI 1.25-8.30). Conclusion Frequency of EMAST was increased in mCRC patients with MSI tumors, compared to MSS tumors. Our data suggest that the presence of EMAST correlates with worse OS in these patients. There was no effect of EMAST on the prognosis of patients with MSS tumors. A limitation of our study is the small number of patients in our subgroup analysis.
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页数:13
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