Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?

IF 2 4区 医学 Q3 ONCOLOGY
Chun-Kai Liao, Yueh-Chen Lin, Yu-Jen Hsu, Yih-Jong Chern, Jeng-Fu You, Jy-Ming Chiang
{"title":"Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?","authors":"Chun-Kai Liao,&nbsp;Yueh-Chen Lin,&nbsp;Yu-Jen Hsu,&nbsp;Yih-Jong Chern,&nbsp;Jeng-Fu You,&nbsp;Jy-Ming Chiang","doi":"10.1186/s13053-021-00186-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients.</p><p><strong>Patients and methods: </strong>Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses.</p><p><strong>Results: </strong>Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup. Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257-0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172-.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219-1.150, p = 0.103) for EC subgroup compared with SC subgroup. Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346-9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788-7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found.</p><p><strong>Conclusions: </strong>Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"29"},"PeriodicalIF":2.0000,"publicationDate":"2021-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243908/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hereditary Cancer in Clinical Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13053-021-00186-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients.

Patients and methods: Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses.

Results: Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup. Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257-0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172-.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219-1.150, p = 0.103) for EC subgroup compared with SC subgroup. Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346-9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788-7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found.

Conclusions: Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.

Abstract Image

Abstract Image

Abstract Image

遗传性非息肉病性结直肠癌患者根据错配修复状态决定手术方式:是应因地制宜,还是一刀切?
背景:虽然延长结肠切除术(EC)被推荐用于HNPCC患者,但先前的研究并未显示总生存率的显著提高。免疫组化(IHC)染色检测错配修复(MMR)基因蛋白表达是目前临床可行、可靠的检测方法。因此,我们试图探讨是否可以使用MMR免疫组化染色选择HNPCC患者的手术类型。患者与方法:1995 ~ 2013年共收集186例HNPCC患者。多因素分析MMR蛋白表达状况、围手术期临床病理变量及术后随访情况。结果:65%的HNPCC患者(186例中的121例)表现出至少一种MMR蛋白的缺失。缺乏MMR (dMMR)亚组和熟练MMR (pMMR)亚组在临床病理特征方面存在一些显著差异。平均随访时间为93.9个月,我们观察到SC和EC亚组发生异时性CRC的风险显著增高(粗率8.5%对0%,p = 0.035)。然而,结肠外肿瘤的存在无显著差异(12.4%比5.8%,p = 0.284)。dMMR亚组异时性结直肠癌的阳性和阴性预测率分别为12.8%和87.2%,pMMR亚组为1.9和98.1%。多因素分析显示,MMR状态和切除类型对生存结果有显著影响。dMMR亚组的OS明显优于pMMR亚组(HR = 0.479, 95% CI: 0.257 ~ 0.894, p = 0.021)。然而,显著改善了DFS (HR = 0.367, 95% CI: 0.172-)。0787, p = 0.010),但与SC亚组相比,EC亚组的OS差异无统计学意义(HR = 0.510, 95% CI: 0.219-1.150, p = 0.103)。结合切除程度和MMR状态,不同亚组间存在差异。多因素分析显示,dMMR亚组中,SC与EC的DFS差异有统计学意义(HR = 3.526, 95% CI: 1.346 ~ 9.236, p = 0.010), OS差异无统计学意义(HR = 2.387, 95% CI: 0.788 ~ 7.229, p = 0.124), pMMR亚组中SC与EC的OS和DFS差异无统计学意义。结论:与pMMR亚组相比,dMMR亚组HNPCC患者的总生存率和异时性结直肠癌发生率显著提高。延长结肠切除术可显著改善DFS,因此推荐用于dMMR亚组而非pMMR亚组的HNPCC患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
3.10
自引率
5.90%
发文量
38
审稿时长
>12 weeks
期刊介绍: Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信