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Colorectal carcinoma grading by quantifying poorly differentiated cell clusters is more reproducible and provides more robust prognostic information than conventional grading

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Abstract

The most widely used system to define the histological grade of colorectal carcinoma (CRC) is based on the degree of gland formation. This system suffers from significant interobserver variability which may limit its prognostic value and consequently better standardized criteria for the assessment of histological grading of CRC are needed. The present study aims to evaluate and to compare, in a cohort of postsurgical pTNM stage I CRC, conventional histological grading, and a novel grading system based on the number of poorly differentiated clusters of neoplastic cells, in terms of interobserver reproducibility, prognostic significance on progression-free survival, and association with other clinicopathological characteristics. Grading with both systems was performed by two pathologists independently and blinded to the clinicopathological data. Interobserver agreement was higher when grade was assessed by counting poorly differentiated clusters than by assessing the relative proportion of the glandular component. Contrary to conventional grading, the novel system provided significant prognostic information in terms of progression-free survival and was significantly associated with budding, invasive growth, lymphatic invasion, and occult nodal metastases of CRC. In conclusion, our findings suggest that a tumor grading system based on the number of poorly differentiated clusters is more reproducible and provides better prognostic stratification of pTNM stage I CRC patients than conventional grading.

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References

  1. Landis SH, Murray T, Bolden S (1999) Cancer statistics. Cancer J Clin 49:8–31

    Article  CAS  Google Scholar 

  2. Wiggers T, Arends JW, Schutter B et al (1988) A multivariate analysis of pathologic prognostic indicators in large bowel cancer. Cancer 61:386–395

    Article  PubMed  CAS  Google Scholar 

  3. Wu XC, Chen VW, Steele B et al (2001) Subsite-specific incidence rate and stage of disease in colorectal cancer by race, gender, and age group. Cancer 92:2547–2554

    Article  Google Scholar 

  4. Di Gregorio C, Fante R, Roncucci L et al (1996) Clinical features, frequency and prognosis of Dukes’ A colorectal carcinoma: a population-based investigation. Eur J Cancer 32A:1957–1962

    Article  PubMed  Google Scholar 

  5. Barresi V, Reggiani-Bonetti L, Di Gregorio C et al (2010) Stage I colorectal carcinoma: vascular endothelial growth factor (VEGF) immunohistochemical expression, microvessel density and their correlation with clinical outcome. Virchows Arch 457:11–19

    Article  PubMed  CAS  Google Scholar 

  6. Barresi V, Ieni A, Reggiani-Bonetti L, Di Gregorio C et al (2011) Neutrophil gelatinase-associated lipocalin (NGAL): a new prognostic marker in stage I colorectal carcinoma? Hum Pathol 42:1720–1726

    Article  PubMed  CAS  Google Scholar 

  7. Barresi V, Reggiani-Bonetti L, Di Gregorio C et al (2011) Lymphatic vessel density and its prognostic value in stage I colorectal carcinoma. J Clin Pathol 64:6–12

    Article  PubMed  CAS  Google Scholar 

  8. Barresi V, Reggiani-Bonetti L, Di Gregorio C et al (2011) Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) prognostic value in stage I colorectal carcinoma. Pathol Res Pract 207:479–486

    Article  PubMed  CAS  Google Scholar 

  9. Barresi V, Reggiani-Bonetti L, Vitarelli E et al (2012) Immunohistochemical assessment of lymphovascular invasion in stage I colorectal carcinoma: prognostic relevance and correlation with nodal micrometastases. Am J Surg Pathol 36:66–72

    Article  PubMed  Google Scholar 

  10. Freedman LS, Macaskill P, Smith AN (1984) Multivariate analysis of prognostic factors for operable rectal cancer. Lancet 29:733–736

    Article  Google Scholar 

  11. Fisher ER, Sass R, Palekar A et al (1989) Dukes’ classification revisited. Findings from the National Surgical Adjuvant Breast and Bowel Projects (Protocol R-01). Cancer 64:2354–2360

    Article  PubMed  CAS  Google Scholar 

  12. Blenkinsopp WK, Stewart-Brown S, Blesovsky L et al (1981) Histopathology reporting in large bowel cancer. J Clin Pathol 34:509–513

    Article  PubMed  CAS  Google Scholar 

  13. Thomas GDH, Dixon MF, Smeeton NC et al (1983) Observer variation in the histological grading of rectal carcinoma. J Clin Pathol 36:385–391

    Article  PubMed  CAS  Google Scholar 

  14. Chandler I, Houlston RS (2008) Interobserver agreement in grading of colorectal cancers-findings from a nationwide web-based survey of histopathologists. Histopathology 52:494–499

    Article  PubMed  CAS  Google Scholar 

  15. Ueno H, Kajiwara Y, Shimazaki H et al (2012) New criteria for histologic grading of colorectal cancer. Am J Surg Pathol 36:193–201

    Article  PubMed  Google Scholar 

  16. Hamilton SR, Volgelstein B, Kudo S et al (2000) Carcinoma of the colon and rectum. In: Hamilton SR, Aaltonen LA (eds) Pathology and genetics of tumours of the digestive system. IARC Press, Lyon, pp 110–111

    Google Scholar 

  17. Hamilton SR, Bosman FT, Boffetta P (2010) Carcinoma of the colon and rectum. In: Bosman T, Carneiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system. IARC Press, Lyon, pp 138–139

    Google Scholar 

  18. Sobin L, Gospodarowicz M, Wittekind C (2009) TNM classification of malignant tumours. Wiley, New York

    Google Scholar 

  19. Kikuchi R, Takano M, Takagi K et al (1995) Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines. Dis Colon Rectum 38:1286–1895

    Article  PubMed  CAS  Google Scholar 

  20. Morodomi T, Isomoto H, Shirouzu G et al (1989) An index for estimating the probability of lymph node metastasis in rectal cancers. Lymph node metastasis and the histopathology of actively invasive regions of cancers. Cancer 63:539–643

    Article  PubMed  CAS  Google Scholar 

  21. Ueno H, Mochizuki H, Hashiguchi Y et al (2004) Preoperative parameters expanding the indication of sphincter preserving surgery in patients with advanced low rectal cancer. Ann Surg 239:34–42

    Article  PubMed  Google Scholar 

  22. Reggiani Bonetti L, Di Gregorio C et al (2011) Lymph node micrometastasis and survival of patients with stage I (Dukes’ A) colorectal carcinoma. Scand J Gastroenterol 46:881–886

    Article  PubMed  Google Scholar 

  23. Lips DJ, Koebrugge B, Liefers GJ et al (2011) The influence of micrometastases on prognosis and survival in stage I–II colon cancer patients: the Enroute study. BMC Surg 11:11

    Article  PubMed  Google Scholar 

  24. Stewart FW, Spies JW (1929) Biopsy histology in the grading of rectal carcinoma. Am J Pathol 5:109–115

    PubMed  CAS  Google Scholar 

  25. Dukes C (1937) Histological grading of rectal cancer. Proc R Soc Med 30:371–376

    PubMed  CAS  Google Scholar 

  26. Grinnell RS (1939) The grading and prognosis of carcinoma of the colon and rectum. Ann Surg 109:500–533

    Article  PubMed  CAS  Google Scholar 

  27. Compton CC, Fielding LP, Burgart LJ et al (2000) Prognostic factors in colorectal cancer. College of American Pathologists consensus statement 1999. Arch Pathol Lab Med 124:979–994

    PubMed  CAS  Google Scholar 

  28. Nicastri DG, Doucette JT, Godfrey TE et al (2007) Is occult lymph node disease in colorectal cancer patients clinically significant? A review of the relevant literature. J Mol Diagn 9:563–571

    Article  PubMed  Google Scholar 

  29. Greenson JK, Isenhart CE, Rice R et al (1994) Identification of occult micrometastases in pericolic lymph nodes of Duke’s B colorectal cancer patients using monoclonal antibodies against cytokeratin and CC49. Correlation with long-term survival. Cancer 73:563–569

    Article  PubMed  CAS  Google Scholar 

  30. Hayashi N, Ito I, Yanagisawa A, Kato Y et al (1995) Genetic diagnosis of lymph node metastasis in colorectal cancer. Lancet 345:1257–1259

    Article  PubMed  CAS  Google Scholar 

  31. Mescoli C, Albertoni L, Pucciarelli S et al (2012) Isolated tumor cells in regional lymph nodes as relapse predictors in stage I and II colorectal cancer. J Clin Oncol 30:965–971

    Article  PubMed  Google Scholar 

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Acknowledgments

We wish to thank Associazione Italiana Ricerca Cancro (AIRC) for financial support.

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We declare that we have no conflict of interest.

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Correspondence to Valeria Barresi.

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Barresi, V., Reggiani Bonetti, L., Branca, G. et al. Colorectal carcinoma grading by quantifying poorly differentiated cell clusters is more reproducible and provides more robust prognostic information than conventional grading. Virchows Arch 461, 621–628 (2012). https://doi.org/10.1007/s00428-012-1326-8

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  • DOI: https://doi.org/10.1007/s00428-012-1326-8

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