Top

Journal of Gastrointestinal Surgery

Published in:

17-01-2023 | Colorectal Cancer | Original Article

The Prognostic Impact of Microsatellite Instability on the Outcome of Appendiceal Adenocarcinoma: a National Cancer Database Analysis

Authors: Sameh Hany Emile, Nir Horesh, Zoe Garoufalia, Rachel Gefen, Peige Zhou, Steven D. Wexner

Published in: Journal of Gastrointestinal Surgery | Issue 2/2023

Abstract

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.

Available only for authorised users

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.CrossRefPubMed

Kelly KJ. Management of Appendix Cancer. Clin Colon Rectal Surg. 2015 Dec;28(4):247-55. https://doi.org/10.1055/s-0035-1564433.CrossRefPubMedPubMedCentral

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.CrossRef

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.CrossRefPubMedPubMedCentral

Halvorsen TB, Seim E. Association between invasiveness, inflammatory reaction, desmoplasia and survival in colorectal cancer. J Clin Pathol 1989;42:162–6.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

10.

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.CrossRefPubMedPubMedCentral

11.

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.CrossRefPubMed

12.

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.CrossRefPubMedPubMedCentral

13.

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.CrossRefPubMedPubMedCentral

14.

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.CrossRefPubMed

15.

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.CrossRefPubMed

16.

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.0000000000010019CrossRef

17.

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/10.1002/1097CrossRef

18.

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.CrossRefPubMed

19.

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.CrossRefPubMedPubMedCentral

20.

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.CrossRefPubMed

21.

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;354:2751–2763CrossRefPubMed

22.

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.CrossRefPubMed

23.

Boland CR. Clinical uses of microsatellite instability testing in colorectal cancer: an ongoing challenge. J Clin Oncol. 2007;25:754–756.CrossRefPubMed

24.

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-zCrossRefPubMedPubMedCentral

25.

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.CrossRefPubMed

Title: The Prognostic Impact of Microsatellite Instability on the Outcome of Appendiceal Adenocarcinoma: a National Cancer Database Analysis
Authors: Sameh Hany Emile
Nir Horesh
Zoe Garoufalia
Rachel Gefen
Peige Zhou
Steven D. Wexner
Publication date: 17-01-2023
Publisher: Springer US
Keywords: Colorectal Cancer
Colorectal Cancer
Published in: Journal of Gastrointestinal Surgery / Issue 2/2023
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-023-05586-z

At a glance: The STEP trials

Springer Medicine

The Prognostic Impact of Microsatellite Instability on the Outcome of Appendiceal Adenocarcinoma: a National Cancer Database Analysis

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2023

Barriers and Facilitators in Implementation of an Esophagectomy Care Pathway: a Qualitative Analysis

Robotic Central Hepatectomy and Right Anterior Sectionectomy: Minimally Invasive Parenchyma Sparing Surgery for Central Liver Tumors

Comparison of Short-Term Surgical Outcomes of Two Types of Robotic Gastrectomy for Gastric Cancer: Ultrasonic Shears Method Versus the Maryland Bipolar Forceps Method

Entero-Gynecologic Fistula: A Rare Complication of Penetrating Crohn’s Disease

Liver Venous Deprivation Versus Portal Vein Embolization Before Major Hepatectomy for Colorectal Liver Metastases: A Retrospective Comparison of Short- and Medium-Term Outcomes

Increased Expression of POSTN Predicts Poor Prognosis: a Potential Therapeutic Target for Gastric Cancer