Combined Microsatellite Instability and Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST) Might Be a More Promising Immune Biomarker in Colorectal Cancer

被引：20

作者：

Chen, Ming-Huang ^{[1
,6
]}

Chang, Shih-Ching ^{[2
,4
,6
]}

Lin, Pei-Ching ^{[7
,8
]}

Yang, Shung-Haur ^{[2
,4
,6
]}

Lin, Chun-Chi ^{[2
,4
,6
]}

Lan, Yuan-Tzu ^{[2
,4
,6
]}

Lin, Hung-Hsin ^{[2
,4
,6
]}

Lin, Chien-Hsing ^{[9
]}

Lai, Jiun-, I ^{[1
,5
,6
]}

Liang, Wen-Yi ^{[3
]}

Lu, Meng-Lun ^{[1
]}

Yang, Muh-Hwa ^{[1
,5
,6
]}

Chao, Yee ^{[1
,6
]}

机构：

[1] Taipei Vet Gen Hosp, Ctr Immunooncol, Dept Oncol, Div Med Oncol, Taipei, Taiwan

[2] Taipei Vet Gen Hosp, Dept Surg, Div Colon & Rectal Surg, Taipei, Taiwan

[3] Taipei Vet Gen Hosp, Dept Pathol, Taipei, Taiwan

[4] Natl Yang Ming Univ, Dept Surg, Fac Med, Taipei, Taiwan

[5] Natl Yang Ming Univ, Inst Clin Med, Taipei, Taiwan

[6] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan

[7] Taipei City Hosp, Dept Clin Pathol, Yang Ming Branch, Taipei, Taiwan

[8] Univ Taipei, Dept Hlth & Welf, Taipei, Taiwan

[9] Natl Hlth Res Inst, Div Genom Med, Zhunan, Taiwan

来源：

ONCOLOGIST | 2019年 / 24卷 / 12期

关键词：

EMAST; Microsatellite instability; Colorectal cancer; Immune biomarkers;

D O I：

10.1634/theoncologist.2019-0171

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background The form of microsatellite instability (MSI) affecting tetranucleotide repeats known as elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has emerged as a new potential biomarker in multiple cancers. In colorectal cancer (CRC), the correlation between EMAST and MSI mutations remain inconclusive. Materials and Methods We evaluated 1,505 patients with CRC using five EMAST markers (D20S82, D20S85, D8S321, D9S242, and MYCL1) and the Bethesda panel of MSI markers. Most commonly, mutations involved in CRCs were identified by MassArray Assay, and DNA repair genes were analyzed by next-generation sequencing. Clinical characteristics and prognostic relevance were correlated with EMAST and MSI. Results Tumors that were EMAST positive and MSI high (MSI-H) were detected in 159 (10.6%) and 154 (10.2%) of 1,505 patients with CRC. Patients were divided into four groups according to EMAST and MSI status (EMAST-positive and MSI-H, EMAST-positive and microsatellite-stable [MSS], EMAST-negative and MSI-H, and EMAST-negative and MSS). The EMAST-positive and MSI-H group was associated with female predominance, higher prevalence of proximal colon tumors, early stage tumors, poorly differentiated tumors, mucinous histology, and higher incidence of mutations in PI3KCA, BRAF, TGFBR, PTEN, and AKT1 compared with other groups. Furthermore, compared with only EMAST-positive tumors or only MSI-H tumors, tumors that were both EMAST-positive and MSI-H had a higher frequency of MLH1, MSH3, MSH6, PMS2, and EXO1 gene mutations. Finally, the presence of EMAST-positive and MSI-H tumors was a good prognostic indicator in CRC. Conclusion High mutations in several DNA repair genes in EMAST-positive and MSI-H tumors suggest that this subtype of CRC might be more suitable for treatment with immune therapy. Implications for Practice Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is a unique molecular subtype of colorectal cancer (CRC). The current study demonstrated that the EMAST-positive and MSI-high (MSI-H) group was associated with female predominance, higher prevalence of proximal colon tumors, early stage tumors, poorly differentiated tumors, mucinous histology, and higher incidence of mutations in PI3KCA, BRAF, TGFBR, PTEN, and AKT1 compared with other groups. Most importantly, high mutations in DNA repair genes and MSI-related genes in EMAST-positive and MSI-H tumors suggest that this subtype of CRC might be more suitable for treatment with immune therapy compared with MSI-H tumors alone.

引用

页码：1534 / 1542

页数：9

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