The Prognostic Impact of Microsatellite Instability on the Outcome of Appendiceal Adenocarcinoma: a National Cancer Database Analysis.
Adenocarcinoma
Appendiceal
Microsatellite instability
NCDB
Overall survival
Journal
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
ISSN: 1873-4626
Titre abrégé: J Gastrointest Surg
Pays: United States
ID NLM: 9706084
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
29
10
2022
accepted:
03
01
2023
pubmed:
18
1
2023
medline:
3
3
2023
entrez:
17
1
2023
Statut:
ppublish
Résumé
Microsatellite instability (MSI) is recognized as a favorable outcome predictor in colorectal cancer. However, its impact on overall survival (OS) of appendiceal carcinoma has not been thoroughly studied. This study aimed to assess the impact of MSI on OS of patients with appendiceal adenocarcinoma, stratified by disease stage, tumor histology, and patients' demographics. This was a retrospective cohort analysis of the colon cancer National Cancer Database (NCDB) between 2005 and 2019. Patients with appendiceal adenocarcinoma with known MSI status were included and subdivided according to MSI status into positive and negative. Primary outcome was OS stratified by MSI status. The study included 1681 (50.1% male) patients with a mean age of 58.9 ± 14.2 years; 211 (12.5%) had MSI-positive tumors (69 MSI low, 53 MSI high, and 89 not specified). Mean 5-year OS of patients with MSI-positive and MSI-negative carcinomas was similar (81.9 versus 78.6 months, p = 0.747). Patients with stage IV MSI-positive carcinomas had significantly longer OS than patients with MSI-negative carcinomas of the same stage (41.3 vs 26.5 months, p = 0.02). Differences in OS for patients with stages I-III were not statistically significant. Compared to MSI-negative/low carcinomas, MSI-high tumors had more advanced pathologic TNM stage (stage III: 23.9% vs 17.8%-stage IV: 41.3% vs 35.4%, p = 0.003), received more chemotherapy (56% vs 41%, p = 0.04), yet had similar OS (81.9 vs 78.9 months, p = 0.357). MSI status of appendiceal adenocarcinomas did not significantly impact survival, except for stage IV disease in which a survival benefit of MSI was noted.
Sections du résumé
BACKGROUND
Microsatellite instability (MSI) is recognized as a favorable outcome predictor in colorectal cancer. However, its impact on overall survival (OS) of appendiceal carcinoma has not been thoroughly studied. This study aimed to assess the impact of MSI on OS of patients with appendiceal adenocarcinoma, stratified by disease stage, tumor histology, and patients' demographics.
METHODS
This was a retrospective cohort analysis of the colon cancer National Cancer Database (NCDB) between 2005 and 2019. Patients with appendiceal adenocarcinoma with known MSI status were included and subdivided according to MSI status into positive and negative. Primary outcome was OS stratified by MSI status.
RESULTS
The study included 1681 (50.1% male) patients with a mean age of 58.9 ± 14.2 years; 211 (12.5%) had MSI-positive tumors (69 MSI low, 53 MSI high, and 89 not specified). Mean 5-year OS of patients with MSI-positive and MSI-negative carcinomas was similar (81.9 versus 78.6 months, p = 0.747). Patients with stage IV MSI-positive carcinomas had significantly longer OS than patients with MSI-negative carcinomas of the same stage (41.3 vs 26.5 months, p = 0.02). Differences in OS for patients with stages I-III were not statistically significant. Compared to MSI-negative/low carcinomas, MSI-high tumors had more advanced pathologic TNM stage (stage III: 23.9% vs 17.8%-stage IV: 41.3% vs 35.4%, p = 0.003), received more chemotherapy (56% vs 41%, p = 0.04), yet had similar OS (81.9 vs 78.9 months, p = 0.357).
CONCLUSIONS
MSI status of appendiceal adenocarcinomas did not significantly impact survival, except for stage IV disease in which a survival benefit of MSI was noted.
Identifiants
pubmed: 36650414
doi: 10.1007/s11605-023-05586-z
pii: 10.1007/s11605-023-05586-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
354-362Informations de copyright
© 2023. The Society for Surgery of the Alimentary Tract.
Références
McCusker M E, Coté T R, Clegg L X, Sobin L H. Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973–1998. Cancer. 2002;94(12):3307–331.
doi: 10.1002/cncr.10589
pubmed: 12115365
Kelly KJ. Management of Appendix Cancer. Clin Colon Rectal Surg. 2015 Dec;28(4):247-55. https://doi.org/10.1055/s-0035-1564433 .
doi: 10.1055/s-0035-1564433
pubmed: 26648795
pmcid: 4655112
Appendiceal cancer. National Cancer Institute. Available online at https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-digestive-system-tumors/appendiceal-cancer#:~:text=The%205%2Dyear%20survival%20rate,body%20can%20be%20much%20lower . Accessed on August 26, 2022.
Xie X, Zhou Z, Song Y, Li W, Diao D, Dang C, Zhang H. The Management and Prognostic Prediction of Adenocarcinoma of Appendix. Sci Rep. 2016 Dec 16;6:39027. https://doi.org/10.1038/srep39027 .
doi: 10.1038/srep39027
Poynter JN, Siegmund KD, Weisenberger DJ, et al. Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening. Cancer Epidemiol Biomarkers Prev 2008;17:3208–15.
doi: 10.1158/1055-9965.EPI-08-0512
pubmed: 18990764
pmcid: 2628332
Halvorsen TB, Seim E. Association between invasiveness, inflammatory reaction, desmoplasia and survival in colorectal cancer. J Clin Pathol 1989;42:162–6.
doi: 10.1136/jcp.42.2.162
pubmed: 2921357
pmcid: 1141819
Koopman M, Kortman GA, Mekenkamp L, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer 2009;100:266–73.
doi: 10.1038/sj.bjc.6604867
pubmed: 19165197
pmcid: 2634718
Gryfe R, Kim H, Hsieh ET, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000;342:69–77.
doi: 10.1056/NEJM200001133420201
pubmed: 10631274
Salem ME, Weinberg BA, Xiu J, El-Deiry WS, Hwang JJ, Gatalica Z, Philip PA, Shields AF, Lenz HJ, Marshall JL. Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers. Oncotarget. 2017 Sep 21;8(49):86356-86368. https://doi.org/10.18632/oncotarget.21169 .
doi: 10.18632/oncotarget.21169
pubmed: 29156800
pmcid: 5689690
Taggart MW, Galbincea J, Mansfield PF, Fournier KF, Royal RE, Overman MJ, Rashid A, Abraham SC. High-level microsatellite instability in appendiceal carcinomas. Am J Surg Pathol. 2013 Aug;37(8):1192-200. https://doi.org/10.1097/PAS.0b013e318282649b .
doi: 10.1097/PAS.0b013e318282649b
pubmed: 23648460
pmcid: 4140656
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013 Mar;48(3):452-8. https://doi.org/10.1038/bmt.2012.244 .
doi: 10.1038/bmt.2012.244
pubmed: 23208313
Morales-Miranda A, Rosado ID, Núñez CC, Montero FC. Appendiceal carcinoma associated with microsatellite instability. Mol Clin Oncol. 2018 May;8(5):694-698. https://doi.org/10.3892/mco.2018.1596 .
doi: 10.3892/mco.2018.1596
pubmed: 29725538
pmcid: 5920207
Kawakami H, Zaanan A, Sinicrope FA. Microsatellite instability testing and its role in the management of colorectal cancer. Curr Treat Options Oncol. 2015 Jul;16(7):30. https://doi.org/10.1007/s11864-015-0348-2 .
doi: 10.1007/s11864-015-0348-2
pubmed: 26031544
pmcid: 4594190
Sinicrope FA, Rego RL, Halling KC, et al. Prognostic impact of microsatellite instability and DNA ploidy in human colon carcinoma patients. Gastroenterology. 2006;131:729–37.
doi: 10.1053/j.gastro.2006.06.005
pubmed: 16952542
Lanza G, Gafa R, Santini A, et al. Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol. 2006;24:2359–67.
doi: 10.1200/JCO.2005.03.2433
pubmed: 16710035
Kang, Sanghee MD, PhDa; Na, Younghyun MDa; Joung, Sung Yup MDa; Lee, Sun Il MD, PhDa; Oh, Sang Cheul MD, PhDb; Min, Byung Wook MD, PhDa,*. The significance of microsatellite instability in colorectal cancer after controlling for clinicopathological factors. Medicine: March 2018 - Volume 97 - Issue 9 - p e0019 https://doi.org/10.1097/MD.0000000000010019
doi: 10.1097/MD.0000000000010019
myrk TC, Watson P, Kaul K, Lynch HT. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer. 2001;91:2417–2422. https://doi.org/10.1002/1097
doi: 10.1002/1097
Phillips SM, Banerjea A, Feakins R, et al. Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic. Br J Surg. 2004;91:469–475.
doi: 10.1002/bjs.4472
pubmed: 15048750
Ogino S, Nosho K, Irahara N, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res. 2009;15:6412–6420.
doi: 10.1158/1078-0432.CCR-09-1438
pubmed: 19825961
pmcid: 2771425
Roth AD, Delorenzi M, Tejpar S, et al. Integrated analysis of molecular and clinical prognostic factors in stage II/III colon cancer. J Natl Cancer Inst. 2012;104:1635–46.
doi: 10.1093/jnci/djs427
pubmed: 23104212
Barnetson RA, Tenesa A, Farrington SM, et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med. 2006;354:2751–2763
doi: 10.1056/NEJMoa053493
pubmed: 16807412
Kim GP, Colangelo LH, Wieand HS, et al. Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol. 2007;25:767–772.
doi: 10.1200/JCO.2006.05.8172
pubmed: 17228023
Boland CR. Clinical uses of microsatellite instability testing in colorectal cancer: an ongoing challenge. J Clin Oncol. 2007;25:754–756.
doi: 10.1200/JCO.2006.09.4607
pubmed: 17228016
Wang, QX., Qu, CH., Gao, YH. et al. The degree of microsatellite instability predicts response to PD-1 blockade immunotherapy in mismatch repair-deficient/microsatellite instability-high colorectal cancers. Exp Hematol Oncol 10, 2 (2021). https://doi.org/10.1186/s40164-020-00193-z
doi: 10.1186/s40164-020-00193-z
pubmed: 33397433
pmcid: 7784284
Kakar S, Aksoy S, Burgart LJ, Smyrk TC. Mucinous carcinoma of the colon: correlation of loss of mismatch repair enzymes with clinicopathologic features and survival. Mod Pathol. 2004 Jun;17(6):696-700. https://doi.org/10.1038/modpathol.3800093 .
doi: 10.1038/modpathol.3800093
pubmed: 15017435