DOI QR코드

DOI QR Code

Carcinoma Microsatellite Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Stage II Rectal Cancer

  • Yang, Liu (Colorectal Cancer Center, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Sun, Yan (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Huang, Xin-En (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Yu, Dong-Sheng (Colorectal Cancer Center, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Zhou, Jian-Nong (Colorectal Cancer Center, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Zhou, Xin (Colorectal Cancer Center, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Li, Dong-Zheng (Colorectal Cancer Center, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Guan, Xin (Colorectal Cancer Center, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research)
  • Published : 2015.03.09

Abstract

Purpose: Rectal cancers with high microsatellite-instable have clinical and pathological features that differentiate them from microsatellite-stable or low-frequency carcinomas, which was studied rarely in stage II rectal cancer, promoting the present investigation of the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II rectal cancer. Patients and Methods: Data of 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2008 to 2012 were retrospectively collected. All patients experienced a total mesorectal excision (TME) operation. Survival analysis were analyzed using the Cox regression method. Results: Five-year rate of disease-free survival (DFS) was noted in 390 (84.8%) of 460 patients with stage II rectal cancer. Of 460 tissue specimens, 97 (21.1%) exhibited high-frequency microsatellite instability. Median age of the patients was 65 (50-71) and 185 (40.2%) were male. After univariate and multivariate analysis, microsatellite instability (p= 0.001), female sex (p<0.05) and fluorouracil-based adjuvant chemotherapy (p<0.001), the 3 factors were attributed to a favorable survival status independently. Among 201 patients who did not receive adjuvant chemotherapy, those cancers displaying high-frequency microsatellite instability had a better 5-year rate of DFS than tumors exhibiting microsatellite stability or low-frequency instability (HR, 13.61 [95% CI, 1.88 to 99.28]; p= 0.010), while in 259 patients who received adjuvant chemotherapy, there was no DFS difference between the two groups (p= 0.145). Furthermore, patients exhibiting microsatellite stability or low-frequency instability who received adjuvant chemotherapy had a better 5-year rate of DFS than patients did not (HR, 5.16 [95% CI, 2.90 to 9.18]; p<0.001), while patients exhibiting high-frequency microsatellite instability were not connected with increased DFS (p= 0.696). It was implied that female patients had better survival than male. Conclusion: Survival status after anterior resection of rectal carcinoma is related to the microsatellite instability status, adjuvant chemotherapy and gender. Fluorouracil-based adjuvant chemotherapy benefits patients of stage II rectal cancer with microsatellite-stable or low microsatellite-instable, but not those with high microsatellite-instable. Additionally, free of adjuvant chemotherapy, carcinomas with high microsatellite-instable have a better 5-year rate of DFS than those with microsatellite-stable or low microsatellite-instable, and female patients have a better survival as well.

Keywords

Rectal cancer;microsatellite instability;survival analysis;adjuvant chemotherapy

References

  1. Ahmedin J, Freddie B, Melissa MC, et al (2011). Global cancer statistics. Ca Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  2. Ahn JB, Chung WB, Maeda O, et al (2011). DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer, 117, 1847-54. https://doi.org/10.1002/cncr.25737
  3. Andre T, Boni C, Navarro M, et al (2009). Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol, 27, 3109-16. https://doi.org/10.1200/JCO.2008.20.6771
  4. Bertagnolli MM, Niedzwiecki D, Compton CC, et al (2009). Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. J Clin Oncol, 27, 1814-21. https://doi.org/10.1200/JCO.2008.18.2071
  5. Chen YS, Xu SX, Ding YB, et al (2013). Helicobacter pylori Infection and the risk of colorectal adenoma and adenocarcinoma: an updated meta-analysis of different testing methods. Asian Pac J Cancer Prev, 14, 7613-9. https://doi.org/10.7314/APJCP.2013.14.12.7613
  6. Chen YS, Xu SX, Ding YB, et al (2014). Colorectal cancer screening in high-risk populations: a survey of cognition among medical professionals in Jiangsu, China. Asian Pac J Cancer Prev, 14, 6487-91.
  7. Cunningham MJ, Christensen ER, Tester DJ, et al (1998). Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res, 58, 3455-60.
  8. Des Guetz G, Schischmanoff O, Nicolas P, et al (2009). Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis. Eur J Cancer, 45, 1890-6. https://doi.org/10.1016/j.ejca.2009.04.018
  9. Gong JP, Yang L, Huang XE, et al (2014). Outcomes based on risk assessment of anastomotic leakage after rectal cancer surgery. Asian Pac J Caner Prev, 15, 707-12. https://doi.org/10.7314/APJCP.2014.15.2.707
  10. Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis (2008). Gastroenterology, 135, 1079-99. https://doi.org/10.1053/j.gastro.2008.07.076
  11. Gryfe R, Kim H, Hsieh ETK, et al (2000). Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med, 342, 69-77. https://doi.org/10.1056/NEJM200001133420201
  12. Halling KC, French AJ, McDonnell SK, et al (1999). Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers. J Natl Cancer Inst, 91, 1295-303. https://doi.org/10.1093/jnci/91.15.1295
  13. Hemminki A, Mecklin JP, Jarvinen H, et al (2000). Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy. Gastroenterology, 119, 921-8. https://doi.org/10.1053/gast.2000.18161
  14. Inamura K, Yamauchi M, Nishihara R, et al (2014). Tumor LINE-1 methylation level and microsatellite instability in relation to colorectal cancer prognosis. J Natl Cancer Inst, 106, dju195.
  15. Kim H, Jen J, Vogelstein B, et al (1994). Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol, 145, 148-56.
  16. Kuismanen SA, Holmberg MT, Salovaara R, et al (2000). Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. Am J Pathol, 156, 1773-9. https://doi.org/10.1016/S0002-9440(10)65048-1
  17. Lanza G, Gafa R, Santini A, et al (2006). Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol, 24, 2359-67. https://doi.org/10.1200/JCO.2005.03.2433
  18. Lengauer C, Kinzler KW, Vogelstein B (1997). Genetic instability in colorectal cancers. Nature, 386, 623-7. https://doi.org/10.1038/386623a0
  19. Lynch HT, Lynch PM, Lanspa SJ, et al (2009). Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet, 76, 1-18.
  20. Midgley R, Kerr DJ (2005). Adjuvant chemotherapy for stage II colorectal cancer: the time is right! Nat Clin Pract Oncol, 2, 364-9. https://doi.org/10.1038/ncponc0228
  21. Popat S, Hubner R, Houlston RS (2005). Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol, 23, 609-18. https://doi.org/10.1200/JCO.2005.01.086
  22. Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatelliteinstability status as a predictor of benefit from fluorouracilbased adjuvant chemotherapy for colon cancer (2003). N Engl J Med, 349, 247-57. https://doi.org/10.1056/NEJMoa022289
  23. Rudolph A, Toth C, Hoffmeister M, et al (2012). Expression of oestrogen receptor ${\beta}$ and prognosis of colorectal cancer. Br J Cancer, 107, 831-9. https://doi.org/10.1038/bjc.2012.323
  24. Thibodeau SN, Bren G, Schaid D (1993). Microsatellite instability in cancer of the proximal colon. Science, 260, 816-9. https://doi.org/10.1126/science.8484122
  25. Oduwole OO, Makinen MJ, Isomaa VV, et al (2003). 17Beta-hydroxysteroid dehydrogenase type 2: independent prognostic significance and evidence of estrogen protection in female patients with colon cancer. J Steroid Biochem Mol Biol, 87, 133-40. https://doi.org/10.1016/j.jsbmb.2003.08.008
  26. Tjandra JJ, Kilkenny JW, Buie WD, et al (2005). Standards practice task force; American society of colon and rectal surgeons. Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum, 48, 411-23. https://doi.org/10.1007/s10350-004-0937-9
  27. Whitehall V, Dumenil T, McKeone D, et al (2014). Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype. Epigenetics, 9, 1454-60. https://doi.org/10.4161/15592294.2014.971624
  28. Wright CM, Dent OF, Barker M, et al (2000). Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer. Br J Surg, 87, 1197-202. https://doi.org/10.1046/j.1365-2168.2000.01508.x
  29. Yang L, Huang XE, Zhou JN (2013). Risk assessment on AL after rectal cancer surgery: an analysis of 753 patients. Asian Pac J Cancer Prev, 14, 4447-53. https://doi.org/10.7314/APJCP.2013.14.7.4447
  30. Yang L, Huang XE, Xu L, et al (2013). Acidic pelvic drainage as a predictive factor for AL after surgery for patients with rectal cancer. Asian Pac J Cancer Prev, 14, 5441-7. https://doi.org/10.7314/APJCP.2013.14.9.5441

Cited by

  1. Clinical Application of Serum Tumor Abnormal Protein (TAP) in Colorectal Cancer Patients vol.16, pp.8, 2015, https://doi.org/10.7314/APJCP.2015.16.8.3425
  2. Safety and Efficacy of a Mouth-Rinse with Granulocyte Colony Stimulating Factor in Patients with Chemotherapy-Induced Oral Mucositis vol.17, pp.1, 2016, https://doi.org/10.7314/APJCP.2016.17.1.413
  3. A Clinical Study on Juheli (Recombinant Human Interleukin - 11) in the Second Prevention of Chemotherapy Induced Thrombocytopenia vol.17, pp.2, 2016, https://doi.org/10.7314/APJCP.2016.17.2.485
  4. Evaluation of Long-Term Outcomes of Microsatellite Instability Status in an Asian Cohort of Sporadic Colorectal Cancers pp.1941-6636, 2017, https://doi.org/10.1007/s12029-017-9953-6