Journal of Pathology and Translational Medicine (대한병리학회지)

The Korean Society of Pathologists (대한병리학회)
권호 표지
DOI QR코드

DOI QR Code

Multiplicity of Advanced T Category-Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma

  • Park, Hye Eun (Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Yoo, Seungyeon (Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Bae, Jeong Mo (Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Jeong, Seorin (Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine) ;
  • Cho, Nam-Yun (Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine) ;
  • Kang, Gyeong Hoon (Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine)
  • Received : 2018.08.14
  • Accepted : 2018.10.02
  • Published : 2018.11.15
⟨ Previous Next ⟩

Abstract

Background: Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods: Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results: SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p=.003) and distant metastasis (p=.001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p<.001), but not for recurrence-free survival (p=.151). Conclusions: Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

Keywords

Acknowledgement

Supported by : National Research Foundation (NRF), Korean Ministry of Health and Welfare

References

  1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-86. https://doi.org/10.1002/ijc.29210
  2. Ghiringhelli F, Hennequin A, Drouillard A, Lepage C, Faivre J, Bouvier AM. Epidemiology and prognosis of synchronous and metachronous colon cancer metastases: a French population-based study. Dig Liver Dis 2014; 46: 854-8. https://doi.org/10.1016/j.dld.2014.05.011
  3. Kaibara N, Koga S, Jinnai D. Synchronous and metachronous malignancies of the colon and rectum in Japan with special reference to a coexisting early cancer. Cancer 1984; 54: 1870-4. https://doi.org/10.1002/1097-0142(19841101)54:9<1870::AID-CNCR2820540917>3.0.CO;2-5
  4. Lam AK, Chan SS, Leung M. Synchronous colorectal cancer: clinical, pathological and molecular implications. World J Gastroenterol 2014; 20: 6815-20. https://doi.org/10.3748/wjg.v20.i22.6815
  5. Oya M, Takahashi S, Okuyama T, Yamaguchi M, Ueda Y. Synchronous colorectal carcinoma: clinico-pathological features and prognosis. Jpn J Clin Oncol 2003; 33: 38-43. https://doi.org/10.1093/jjco/hyg010
  6. Yang J, Peng JY, Chen W. Synchronous colorectal cancers: a review of clinical features, diagnosis, treatment, and prognosis. Dig Surg 2011; 28: 379-85. https://doi.org/10.1159/000334073
  7. Cunliffe WJ, Hasleton PS, Tweedle DE, Schofield PF. Incidence of synchronous and metachronous colorectal carcinoma. Br J Surg 1984; 71: 941-3. https://doi.org/10.1002/bjs.1800711210
  8. Evers BM, Mullins RJ, Matthews TH, Broghamer WL, Polk HC Jr. Multiple adenocarcinomas of the colon and rectum: an analysis of incidences and current trends. Dis Colon Rectum 1988; 31: 518-22. https://doi.org/10.1007/BF02553724
  9. Fukatsu H, Kato J, Nasu JI, et al. Clinical characteristics of synchronous colorectal cancer are different according to tumour location. Dig Liver Dis 2007; 39: 40-6. https://doi.org/10.1016/j.dld.2006.07.015
  10. Hu H, Chang DT, Nikiforova MN, Kuan SF, Pai RK. Clinicopathologic features of synchronous colorectal carcinoma: a distinct subset arising from multiple sessile serrated adenomas and associated with high levels of microsatellite instability and favorable prognosis. Am J Surg Pathol 2013; 37: 1660-70. https://doi.org/10.1097/PAS.0b013e31829623b8
  11. Kimura T, Iwagaki H, Fuchimoto S, Hizuta A, Orita K. Synchronous colorectal carcinomas. Hepatogastroenterology 1994; 41: 409-12.
  12. Latournerie M, Jooste V, Cottet V, Lepage C, Faivre J, Bouvier AM. Epidemiology and prognosis of synchronous colorectal cancers. Br J Surg 2008; 95: 1528-33. https://doi.org/10.1002/bjs.6382
  13. Mulder SA, Kranse R, Damhuis RA, et al. Prevalence and prognosis of synchronous colorectal cancer: a Dutch population-based study. Cancer Epidemiol 2011; 35: 442-7. https://doi.org/10.1016/j.canep.2010.12.007
  14. Ueno M, Muto T, Oya M, Ota H, Azekura K, Yamaguchi T. Multiple primary cancer: an experience at the Cancer Institute Hospital with special reference to colorectal cancer. Int J Clin Oncol 2003; 8: 162-7. https://doi.org/10.1007/s10147-003-0322-z
  15. Wang HZ, Huang XF, Wang Y, Ji JF, Gu J. Clinical features, diagnosis, treatment and prognosis of multiple primary colorectal carcinoma. World J Gastroenterol 2004; 10: 2136-9. https://doi.org/10.3748/wjg.v10.i14.2136
  16. Kato T, Alonso S, Muto Y, et al. Clinical characteristics of synchronous colorectal cancers in Japan. World J Surg Oncol 2016; 14: 272. https://doi.org/10.1186/s12957-016-1027-x
  17. Chen HS, Sheen-Chen SM. Synchronous and “early” metachronous colorectal adenocarcinoma: analysis of prognosis and current trends. Dis Colon Rectum 2000; 43: 1093-9. https://doi.org/10.1007/BF02236556
  18. Finan PJ, Ritchie JK, Hawley PR. Synchronous and 'early' metachronous carcinomas of the colon and rectum. Br J Surg 1987; 74: 945-7. https://doi.org/10.1002/bjs.1800741021
  19. Kim YJ, Kim NK, Lee KY, Sohn SK, Min JS. Clinicopathological characteristics of multiple primary colorectal cancer. J Korean Soc Coloproctol 2002; 18: 343-8.
  20. Kang JG, Kim DH, Kim CH, Lee SH, Choi YJ. Clinical characteristics of synchronous multiple colorectal cancer. J Korean Soc Coloproctol 2006; 22: 418-23.
  21. Welch JP. Multiple colorectal tumors: an appraisal of natural history and therapeutic options. Am J Surg 1981; 142: 274-80. https://doi.org/10.1016/0002-9610(81)90292-0
  22. Lam AK, Carmichael R, Gertraud Buettner P, Gopalan V, Ho YH, Siu S. Clinicopathological significance of synchronous carcinoma in colorectal cancer. Am J Surg 2011; 202: 39-44. https://doi.org/10.1016/j.amjsurg.2010.05.012
  23. Pedroni M, Tamassia MG, Percesepe A, et al. Microsatellite instability in multiple colorectal tumors. Int J Cancer 1999; 81: 1-5. https://doi.org/10.1002/(SICI)1097-0215(19990331)81:1<1::AID-IJC1>3.0.CO;2-K
  24. Norrie MW, Hawkins NJ, Todd AV, Meagher AP, O'Connor TW, Ward RL. The role of hMLH1 methylation in the development of synchronous sporadic colorectal carcinomas. Dis Colon Rectum 2002; 45: 674-80. https://doi.org/10.1007/s10350-004-6266-1
  25. Dykes SL, Qui H, Rothenberger DA, Garcia-Aguilar J. Evidence of a preferred molecular pathway in patients with synchronous colorectal cancer. Cancer 2003; 98: 48-54. https://doi.org/10.1002/cncr.11445
  26. Nosho K, Kure S, Irahara N, et al. A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers. Gastroenterology 2009; 137: 1609-20.e1-3. https://doi.org/10.1053/j.gastro.2009.08.002
  27. Gonzalo V, Lozano JJ, Alonso-Espinaco V, et al. Multiple sporadic colorectal cancers display a unique methylation phenotype. PLoS One 2014; 9: e91033. https://doi.org/10.1371/journal.pone.0091033
  28. Brueckl WM, Limmert T, Brabletz T, et al. Mismatch repair deficiency in sporadic synchronous colorectal cancer. Anticancer Res 2000; 20: 4727-32.
  29. Kamiyama H, Suzuki K, Maeda T, et al. DNA demethylation in normal colon tissue predicts predisposition to multiple cancers. Oncogene 2012; 31: 5029-37. https://doi.org/10.1038/onc.2011.652
  30. Eguchi K, Yao T, Konomoto T, Hayashi K, Fujishima M, Tsuneyoshi M. Discordance of p53 mutations of synchronous colorectal carcinomas. Mod Pathol 2000; 13: 131-9. https://doi.org/10.1038/modpathol.3880024
  31. Giannini R, Lupi C, Loupakis F, et al. KRAS and BRAF genotyping of synchronous colorectal carcinomas. Oncol Lett 2014; 7: 1532-6. https://doi.org/10.3892/ol.2014.1905
  32. Ronnekleiv-Kelly SM, Pawlik TM. Staging of intrahepatic cholangiocarcinoma. Hepatobiliary Surg Nutr 2017; 6: 35-43. https://doi.org/10.21037/hbsn.2016.10.02
  33. Enker WE, Dragacevic S. Multiple carcinomas of the large bowel: a natural experiment in etiology and pathogenesis. Ann Surg 1978; 187: 8-11. https://doi.org/10.1097/00000658-197801000-00002
  34. Bae JM, Kim JH, Cho NY, Kim TY, Kang GH. Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location. Br J Cancer 2013; 109: 1004-12. https://doi.org/10.1038/bjc.2013.430
  35. Oh HJ, Bae JM, Wen XY, Cho NY, Kim JH, Kang GH. Overexpression of POSTN in tumor stroma is a poor prognostic indicator of colorectal cancer. J Pathol Transl Med 2017; 51: 306-13. https://doi.org/10.4132/jptm.2017.01.19
  36. Bae JM, Kim JH, Kang GH. Molecular subtypes of colorectal cancer and their clinicopathologic features, with an emphasis on the serrated neoplasia pathway. Arch Pathol Lab Med 2016; 140: 406-12. https://doi.org/10.5858/arpa.2015-0310-RA

Cited by

  1. Reveal the Regulation Patterns of Prognosis-Related miRNAs and lncRNAs Across Solid Tumors in the Cancer Genome Atlas vol.8, pp.None, 2018, https://doi.org/10.3389/fcell.2020.00368
  2. Whole-Slide Image Analysis Reveals Quantitative Landscape of Tumor–Immune Microenvironment in Colorectal Cancers vol.26, pp.4, 2020, https://doi.org/10.1158/1078-0432.ccr-19-1159