MSI-H/dMMR对BRAF V600E突变型的手术可切除结直肠癌患者的临床病理学特征及预后的影响

doi:10.19401/j.cnki.1007-3639.2024.11.009

摘要/Abstract

关键词: 结直肠癌, BRAF V600E突变, 错配修复缺陷, 微卫星不稳定性, 预后

Key words: Colorectal cancer, BRAF V600E mutation, Mismatch repair deficiency, Microsatellite instability, Prognosis

中图分类号:

R735.3

李军, 陆亭伟, 方旭前. MSI-H/dMMR对BRAF V600E突变型的手术可切除结直肠癌患者的临床病理学特征及预后的影响[J]. 中国癌症杂志, 2024, 34(11): 1061-1066.

LI Jun, LU Tingwei, FANG Xuqian. Impact of MSI-H/dMMR on clinicopathological characteristics and prognosis of patients with BRAF V600E-mutated resectable colorectal cancer[J]. China Oncology, 2024, 34(11): 1061-1066.

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参考文献 28

[1]	VILAR E, GRUBER S B. Microsatellite instability in colorectal cancer-the stable evidence[J]. Nat Rev Clin Oncol, 2010, 7(3): 153-162. doi: 10.1038/nrclinonc.2009.237 pmid: 20142816
[2]	中国临床肿瘤学会结直肠癌专家委员会, 中国抗癌协会大肠癌专业委员会遗传学组, 中国医师协会结直肠肿瘤专业委员会遗传专委会. 结直肠癌及其他相关实体瘤微卫星不稳定性检测中国专家共识[J]. 中华肿瘤杂志, 2019. 41(10): 734-741.
	The Colorectal Cancer Expert Committee of Chinese Society of Clinical Oncology, the Genetics Group of the Colorectal Cancer Professional Committee of China Anti-Cancer Association, and the Genetics Committee of the Colorectal Cancer Professional Committee of Chinese Medical Doctor Association. Consensus on the detection of microsatellite instability in colorectal cancer and other related solid tumors in China[J]. Chin J Oncol, 2019. 41(10): 734-741.
[3]	黎相照, 刘焕娇, 梁敏仪, 等. 微卫星不稳定性类型及临床病理特征:基于1394例结直肠癌患者的标本检测[J]. 南方医科大学学报, 2020, 40(11): 1645-1650. doi: 10.12122/j.issn.1673-4254.2020.11.17
	LI X Z, LIU H J, LIANG M Y, et al. Clinicopathological features and types of microsatellite instability in 1394 patients with colorectal cancer[J]. J South Med Univ, 2020, 40(11): 1645-1650.
[4]	DIENSTMANN R, VERMEULEN L, GUINNEY J, et al. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer[J]. Nat Rev Cancer, 2017, 17(2): 79-92. doi: 10.1038/nrc.2016.126 pmid: 28050011
[5]	GROTHEY A, FAKIH M, TABERNERO J. Management of BRAF-mutant metastatic colorectal cancer: a review of treatment options and evidence-based guidelines[J]. Ann Oncol, 2021, 32(8): 959-967. doi: 10.1016/j.annonc.2021.03.206 pmid: 33836264
[6]	Chinese Society of Clinical Oncology Diagnosis and Treatment Guidelines for Colorectal Cancer Working Group. Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines for colorectal cancer 2018 (English version)[J]. Chin J Cancer Res, 2019, 31(1): 117-134.
[7]	OLIVEIRA A F, BRETES L, FURTADO I. Review of PD-1/PD-L1 inhibitors in metastatic dMMR/MSI-H colorectal cancer[J]. Front Oncol, 2019, 9: 396. doi: 10.3389/fonc.2019.00396 pmid: 31139574
[8]	SARIDAKI Z, SOUGLAKOS J, GEORGOULIAS V. Prognostic and predictive significance of MSI in stages Ⅱ/Ⅲ colon cancer[J]. World J Gastroenterol, 2014, 20(22): 6809-6814.
[9]	HESTETUN K E, ROSENLUND N B, STANISAVLJEVIĆ L, et al. Stage-dependent prognostic shift in mismatch repair-deficient tumors: assessing patient outcomes in stage Ⅱ and Ⅲ colon cancer[J]. Front Oncol, 2022, 12: 853545.
[10]	FUJIYOSHI K, YAMAMOTO G, TAKENOYA T, et al. Metastatic pattern of stage Ⅳ colorectal cancer with high-frequency microsatellite instability as a prognostic factor[J]. Anticancer Res, 2017, 37(1): 239-247.
[11]	LOUPAKIS F, CREMOLINI C, MASI G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer[J]. N Engl JMed, 2014, 371(17): 1609-1618.
[12]	MAURI G, BONAZZINA E, AMATU A, et al. The evolutionary landscape of treatment for BRAF V600E mutant metastatic colorectal cancer[J]. Cancers, 2021, 13(1): 137.
[13]	GUINNEY J, DIENSTMANN R, WANG X, et al. The consensus molecular subtypes of colorectal cancer[J]. Nat Med, 2015, 21(11): 1350-1356. doi: 10.1038/nm.3967 pmid: 26457759
[14]	JOANITO I, WIRAPATI P, ZHAO N, et al. Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer[J]. Nat Genet, 2022, 54(7): 963-975.
[15]	郑民华, 张森, 马君俊. 结直肠癌的分子分型与精准治疗策略:从经验到精确[J]. 中华消化外科杂志, 2023, 22(10): 1155-1159.
	ZHENG M H, ZHANG S, MA J J. Molecular typing and precise treatment strategies for colorectal cancer: from experience to precision[J]. Chin j Dig Surg, 2023, 22(10): 1155-1159.
[16]	LIU Q, LUO D K, CAI S J, et al. P-TNM staging system for colon cancer: combination of P-stage and AJCC TNM staging system for improving prognostic prediction and clinical management[J]. Cancer Manag Res, 2018, 10: 2303-2314. doi: 10.2147/CMAR.S165188 pmid: 30104899
[17]	HATCH S B, LIGHTFOOT H M JR, GARWACKI C P, et al. Microsatellite instability testing in colorectal carcinoma: choice of markers affects sensitivity of detection of mismatch repair-deficient tumors[J]. Clin Cancer Res, 2005, 11(6): 2180-2187. doi: 10.1158/1078-0432.CCR-04-0234 pmid: 15788665
[18]	COLLE R, LONARDI S, CACHANADO M, et al. BRAF V600E/RAS mutations and Lynch syndrome in patients with MSI-H/dMMR metastatic colorectal cancer treated with immune checkpoint inhibitors[J]. Oncologist, 2023, 28(9): 771-779. doi: 10.1093/oncolo/oyad082 pmid: 37023721
[19]	VENDERBOSCH S, NAGTEGAAL I D, MAUGHAN T S, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies[J]. Clin Cancer Res, 2014, 20(20): 5322-5330. doi: 10.1158/1078-0432.CCR-14-0332 pmid: 25139339
[20]	AASEBØ K Ø, DRAGOMIR A, SUNDSTRÖM M, et al. Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: a population-based cohort of metastatic colorectal cancer patients[J]. Cancer Med, 2019, 8(7): 3623-3635.
[21]	杨利华, 杨树东. RAS、BRAF基因突变及HER2基因扩增与结直肠癌患者临床病理特征及预后的关系[J]. 中华普通外科杂志, 2022, 37(11): 845-849.
	YANG L H, YANG S D. Relationship between RAS, BRAF gene mutations and HER2 gene amplification and clinicopathology and prognosis of colorectal cancer[J]. Chin J Gen Surg, 2022, 37(11): 845-849.
[22]	YAEGER R, CERCEK A, CHOU J F, et al. BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer[J]. Cancer, 2014, 120(15): 2316-2324.
[23]	TAIEB J, SVRCEK M, COHEN R, et al. Deficient mismatch repair/microsatellite unstable colorectal cancer: diagnosis, prognosis and treatment[J]. Eur J Cancer, 2022, 175: 136-157. doi: 10.1016/j.ejca.2022.07.020 pmid: 36115290
[24]	NAKAYAMA I, HIROTA T, SHINOZAKI E. BRAF mutation in colorectal cancers: from prognostic marker to targetable mutation[J]. Cancers, 2020, 12(11): 3236.
[25]	KARKI S, SUN W J, MADAN R, et al. Microsatellite instability with BRAF V600E associated with delayed presentation but poor survival in stage Ⅲ colorectal cancer[J]. Fortune J Health Sci, 2023, 6(2): 167-173.
[26]	DIAZ L A JR, SHIU K K, KIM T W, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study[J]. Lancet Oncol, 2022, 23(5): 659-670. doi: 10.1016/S1470-2045(22)00197-8 pmid: 35427471
[27]	DING Y W, WENG S S, LI X Y, et al. General treatment for metastatic colorectal cancer: from KEYNOTE 177 study[J]. Transl Oncol, 2021, 14(8): 101122.
[28]	JOHNSON B, KOPETZ S. Applying precision to the management of BRAF-mutant metastatic colorectal cancer[J]. Target Oncol, 2020, 15(5): 567-577.

Characteristic	BRAF＋ (n=54)	BRAF＋, MSS (n=38)	BRAF＋, MSI-H/dMMR (n=16)	χ^{2 value}	P value
Gender n				4.15	0.042
Male	25	21	4
Female	29	17	12
Age/year $\bar{x}±s$	65.59±12.92	62.39±13.02	73.19±9.19		0.004^#
Location n				4.88	0.027
Left half	26	22	4
Right half	28	16	12
dMMR n (%)
MLH1-	16 (29.7)	0 (0.0)	16 (100.0)
PMS2-	16 (29.7)	0 (0.0)	16 (100.0)
MSH2-	0 (0.0)	0 (0.0)	0 (0.0)
MSH6-	0 (0.0)	0 (0.0)	0 (0.0)
Colorectal cancer radical surgery n (%)	51 (94.4)	35 (92.1)	16 (100.0)		0.546^#
T stage n				1.50	0.682
T1	4	2	2
T2	1	1	0
T3	36	25	11
T4	13	10	3
N stage n				16.34	0.000
N0	25	11	14
N1	13	11	2
N2	16	16	0
M stage n				5.816	0.016
M0	43	27	16
M1	11	11	0
Clinical stage n				21.39	<0.0001
Ⅰ	4	2	2
Ⅱ	18	6	12
Ⅲ	20	18	2
Ⅳ	12	12	0

MSI-H/dMMR对BRAF V600E突变型的手术可切除结直肠癌患者的临床病理学特征及预后的影响

Impact of MSI-H/dMMR on clinicopathological characteristics and prognosis of patients with BRAF V600E-mutated resectable colorectal cancer

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