Association of KRAS Mutation with Tumor Deposit Status and Overall Survival of Colorectal Cancer

Overview

Journal Cancer Causes Control

Specialties Oncology
Public Health

Date 2020 May 13

PMID 32394229

Citations 6

Authors

Meifang Zhang

Wenwei Hu

Kun Hu

Yong Lin

Zhaohui Feng

Jing-Ping Yun

Nan Gao

Lanjing Zhang

Affiliations

Soon will be listed here.

Abstract

Purpose: To examine associations of KRAS mutation with tumor deposit status and overall survival in colorectal cancer (CRC) patients.

Methods: This retrospective cohort study included patients with incidental CRC diagnosed during 2010-2014 and recorded statuses of KRAS and tumor deposit in the National Cancer Database of the USA. Multivariable logistic regression and time-varying Cox regression analyses were used.

Results: We included 45,761 CRC patients with KRAS status (24,027 [52.5%] men, 24,240 [53.0%] < 65 years old, 17,338 [37.9%] with KRAS mutation). Adjusted for microsatellite instability, age, pathologic stage and tumor grade, KRAS mutation (versus wild type) was associated with tumor deposit presence (odds ratio = 1.11, 95% CI 1.02-1.20). KRAS mutation was also linked to worse overall survival of CRC patients regardless of tumor deposit status (adjusted Hazard ratio [HR] = 1.20, 95% CI 1.07-1.33 for CRC with tumor deposits, and adjusted HR = 1.24, 95% CI 1.14-1.35 or CRC without) or tumor stage (adjusted HR = 1.32, 95% CI 1.14-1.54 for early-stage and adjusted HR = 1.18, 95% CI 1.10-1.27 for late-stage). Microsatellite instability was associated with better overall survival in CRC without tumor deposit (adjusted HR = 0.89, 95% CI 0.79-0.99), but not in CRC with tumor deposit (adjusted HR = 1.12, 95% CI 0.97-1.30).

Conclusion: KRAS mutation is independently associated with tumor deposit presence and a worse overall survival in CRC patients.

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References

Siegel R, Miller K, Jemal A . Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1):7-30. DOI: 10.3322/caac.21590. View

Nagata Y, Abe M, Kobayashi K, Yoshida K, Ishibashi T, Naoe T . Glycine to aspartic acid mutations at codon 13 of the c-Ki-ras gene in human gastrointestinal cancers. Cancer Res. 1990; 50(3):480-2. View

Maughan T, Adams R, Smith C, Meade A, Seymour M, Wilson R . Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011; 377(9783):2103-14. PMC: 3159415. DOI: 10.1016/S0140-6736(11)60613-2. View

Goodman C, Seagle B, Friedl T, Rack B, Lato K, Fink V . Association of Circulating Tumor Cell Status With Benefit of Radiotherapy and Survival in Early-Stage Breast Cancer. JAMA Oncol. 2018; 4(8):e180163. PMC: 6143053. DOI: 10.1001/jamaoncol.2018.0163. View

Andreyev H, Norman A, Cunningham D, Oates J, Clarke P . Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study. J Natl Cancer Inst. 1998; 90(9):675-84. DOI: 10.1093/jnci/90.9.675. View

Puppa G, Maisonneuve P, Sonzogni A, Masullo M, Capelli P, Chilosi M . Pathological assessment of pericolonic tumor deposits in advanced colonic carcinoma: relevance to prognosis and tumor staging. Mod Pathol. 2007; 20(8):843-55. DOI: 10.1038/modpathol.3800791. View

Ogino S, Meyerhardt J, Irahara N, Niedzwiecki D, Hollis D, Saltz L . KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. Clin Cancer Res. 2009; 15(23):7322-9. PMC: 2787689. DOI: 10.1158/1078-0432.CCR-09-1570. View

Song J, Chang H, Kim D, Kim S, Baek J, Park J . Is the N1c category of the new American Joint Committee on cancer staging system applicable to patients with rectal cancer who receive preoperative chemoradiotherapy?. Cancer. 2011; 117(17):3917-24. DOI: 10.1002/cncr.25968. View

Mayo E, Llanos A, Yi X, Duan S, Zhang L . Prognostic value of tumour deposit and perineural invasion status in colorectal cancer patients: a SEER-based population study. Histopathology. 2016; 69(2):230-8. DOI: 10.1111/his.12936. View

10.

Finkelstein S, Sayegh R, Christensen S, Swalsky P . Genotypic classification of colorectal adenocarcinoma. Biologic behavior correlates with K-ras-2 mutation type. Cancer. 1993; 71(12):3827-38. DOI: 10.1002/1097-0142(19930615)71:12<3827::aid-cncr2820711207>3.0.co;2-n. View

11.

Zaanan A, Shi Q, Taieb J, Alberts S, Meyers J, Smyrk T . Role of Deficient DNA Mismatch Repair Status in Patients With Stage III Colon Cancer Treated With FOLFOX Adjuvant Chemotherapy: A Pooled Analysis From 2 Randomized Clinical Trials. JAMA Oncol. 2017; 4(3):379-383. PMC: 5784452. DOI: 10.1001/jamaoncol.2017.2899. View

12.

Nagayoshi K, Ueki T, Nishioka Y, Manabe T, Mizuuchi Y, Hirahashi M . Tumor deposit is a poor prognostic indicator for patients who have stage II and III colorectal cancer with fewer than 4 lymph node metastases but not for those with 4 or more. Dis Colon Rectum. 2014; 57(4):467-74. DOI: 10.1097/DCR.0000000000000059. View

13.

Sargent D, Marsoni S, Monges G, Thibodeau S, Labianca R, Hamilton S . Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010; 28(20):3219-26. PMC: 2903323. DOI: 10.1200/JCO.2009.27.1825. View

14.

Tateishi S, Arima S, Futami K, Kawahara K, Tachikawa D, Naritomi K . A clinicopathological investigation of "tumor nodules" in colorectal cancer. Surg Today. 2005; 35(5):377-84. DOI: 10.1007/s00595-004-2950-y. View

15.

De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G . Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010; 11(8):753-62. DOI: 10.1016/S1470-2045(10)70130-3. View

16.

Shaw P, Tardy S, Benito E, Obrador A, Costa J . Occurrence of Ki-ras and p53 mutations in primary colorectal tumors. Oncogene. 1991; 6(11):2121-8. View

17.

Engstrom P, Arnoletti J, Benson 3rd A, Chen Y, Choti M, Cooper H . NCCN Clinical Practice Guidelines in Oncology: colon cancer. J Natl Compr Canc Netw. 2009; 7(8):778-831. DOI: 10.6004/jnccn.2009.0056. View

18.

Joshi S, Handorf E, Strauss D, Correa A, Kutikov A, Chen D . Treatment Trends and Outcomes for Patients With Lymph Node-Positive Cancer of the Penis. JAMA Oncol. 2018; 4(5):643-649. PMC: 5885184. DOI: 10.1001/jamaoncol.2017.5608. View

19.

Jover R, Zapater P, Castells A, Llor X, Andreu M, Cubiella J . Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer. Gut. 2005; 55(6):848-55. PMC: 1856227. DOI: 10.1136/gut.2005.073015. View

20.

Pezzi T, Schwartz D, Mohamed A, Welsh J, Komaki R, Hahn S . Barriers to Combined-Modality Therapy for Limited-Stage Small Cell Lung Cancer. JAMA Oncol. 2018; 4(8):e174504. PMC: 5885163. DOI: 10.1001/jamaoncol.2017.4504. View