The prognostic value of signet ring cell histology in stage I/II colon cancer—a population-based, propensity score-matched analysis
Previous research associated signet ring cell histology in colon cancer patients with poor survival outcomes. The aim of this study was to analyze the prognostic significance of signet ring cell histology on overall and cancer-specific survival in patients with localized colon cancer.
Stage I and II colon cancer patients treated with surgical resection between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods.
Eighty-eight thousand nine hundred fifty-eight stage I–II colon cancer patients were identified. Overall, 446 (0.5%) showed signet ring cell histology. In unadjusted analyses, the 5-year OS and CSS rates of patients with signet ring cell histology were 65.8 and 83.1%, respectively, compared with 74.3 and 88.7% in patients with non-signet ring cell adenocarcinoma (p values: OS, p < 0.001; CSS, p < 0.001). Neither in risk-adjusted Cox proportional hazard regression analysis (OS: hazard ratio (HR), 0.96 (95% CI, 0.82–1.12%) p = 0.616; CSS: HR, 1.01 (95% CI, 0.79–1.28%) p = 0.946) nor with propensity score matching (OS: HR, 0.96 (95% CI, 0.82–1.14%) p = 0.669 and CSS: HR: 1.09 (95% CI: 0.84–1.40%) p = 0.529), a survival disadvantage was found for signet ring cell histology.
This is the first propensity score-adjusted population-based investigation on exclusively stage I and II colon cancer patients providing compelling evidence that signet ring cell histology does not negatively impact survival in stage I and II colon cancer after risk-adjusting for known prognostic factors. Therefore, standard treatment strategies can be applied in these patients.
KeywordsSurvival Colon cancer Adenocarcinoma Signet ring carcinoma, Surveillance, Epidemiology, and End Results Program SEER Propensity score
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 4.Bosman FT et al (2010) 4th Edition of the WHO classification of tumours of the digestive system. International Agency for Research on Cancer, GenevaGoogle Scholar
- 5.Hyngstrom JR, Hu CY, Xing Y, You YN, Feig BW, Skibber JM, Rodriguez-Bigas MA, Cormier JN, Chang GJ (2012) Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma: analysis from the National Cancer Data Base. Ann Surg Oncol 19(9):2814–2821CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Lee DW, Han SW, Lee HJ, Rhee YY, Bae JM, Cho NY, Lee KH, Kim TY, Oh DY, Im SA, Bang YJ, Jeong SY, Park KJ, Park JG, Kang GH, Kim TY (2013) Prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX chemotherapy. Br J Cancer 108(10):1978–1984CrossRefPubMedPubMedCentralGoogle Scholar
- 10.National Cancer Institute, Surveillance, Epidemiology, and End Results Program (SEER) Research Data (1973–2015) released April 2018, based on the November 2017 submission. available at http://www.seer.cancer.gov/ (Last accessed April 29, 2018). 2017
- 11.Wingo PA, Jamison PM, Hiatt RA, Weir HK, Gargiullo PM, Hutton M, Lee NC, Hall HI (2003) Building the infrastructure for nationwide cancer surveillance and control—a comparison between the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology, and End Results (SEER) Program (United States). Cancer Causes Control 14(2):175–193CrossRefPubMedGoogle Scholar
- 12.Fritz A et al (2000) International classification of disease for oncology (ed. 3). World Health Organization, Geneva, SwitzerlandGoogle Scholar
- 16.Inamura K, Yamauchi M, Nishihara R, Kim SA, Mima K, Sukawa Y, Li T, Yasunari M, Zhang X, Wu K, Meyerhardt JA, Fuchs CS, Harris CC, Qian ZR, Ogino S (2015) Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma. Ann Surg Oncol 22(4):1226–1235CrossRefPubMedGoogle Scholar
- 17.Nitsche U, Zimmermann A, Späth C, Müller T, Maak M, Schuster T, Slotta-Huspenina J, Käser SA, Michalski CW, Janssen KP, Friess H, Rosenberg R, Bader FG (2013) Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis. Ann Surg 258(5):775–782 discussion 782–3CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Nitsche U, Friess H, Agha A, Angele M, Eckel R, Heitland W, Jauch KW, Krenz D, Nüssler NC, Rau HG, Ruppert R, Schubert-Fritschle G, Wilhelm D, Werner J, Engel J (2016) Prognosis of mucinous and signet-ring cell colorectal cancer in a population-based cohort. J Cancer Res Clin Oncol 142(11):2357–2366CrossRefPubMedGoogle Scholar
- 20.Catalano V, Loupakis F, Graziano F, Bisonni R, Torresi U, Vincenzi B, Mari D, Giordani P, Alessandroni P, Salvatore L, Fornaro L, Santini D, Baldelli AM, Rossi D, Giustini L, Silva RR, Falcone A, D'Emidio S, Rocchi M, Luzi Fedeli S (2012) Prognosis of mucinous histology for patients with radically resected stage II and III colon cancer. Ann Oncol 23(1):135–141CrossRefPubMedGoogle Scholar
- 21.Du W et al (2004) Incidence and survival of mucinous adenocarcinoma of the colorectum: a population-based study from an Asian country. Dis Colon rectum 47(1):78–85Google Scholar
- 25.Leopoldo S, Lorena B, Cinzia A, Gabriella DC, Angela Luciana B, Renato C, Antonio M, Carlo S, Cristina P, Stefano C, Maurizio T, Luigi R, Cesare B (2008) Two subtypes of mucinous adenocarcinoma of the colorectum: clinicopathological and genetic features. Ann Surg Oncol 15(5):1429–1439CrossRefPubMedGoogle Scholar
- 28.Twelves C, Wong A, Nowacki MP, Abt M, Burris H III, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, van Hazel G, Zaluski J, Scheithauer W (2005) Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352(26):2696–2704CrossRefPubMedGoogle Scholar
- 31.Andre T et al (2018) Three versus 6 months of oxaliplatin-based adjuvant chemotherapy for patients with stage iii colon cancer: disease-free survival results from a randomized, open-label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial. J Clin Oncol 36(15):1469-1477Google Scholar