Accuracy of TNM staging in colorectal cancer: a review of current culprits, the modern role of morphology and stepping-stones for improvements in the molecular era

References

• Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet 2010;375:1030–47.
   PubMed Web of Science ®Google Scholar
• Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB. Cancer incidence in five continents. Volume VIII. IARC Sci Publ 2002:1–781.
   PubMedGoogle Scholar
• Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin 2009;59:366–78.
   PubMed Web of Science ®Google Scholar
• Kodeda K, Nathanaelsson L, Jung B, Olsson H, Jestin P, Sjovall A, et al. Population-based data from the Swedish Colon Cancer Registry. Br J Surg 2013;100:1100–7.
   PubMed Web of Science ®Google Scholar
• Nedrebø BS, Søreide K, Eriksen MT, Dørum LM, Kvaloy JT, Soreide JA, et al. Survival effect of implementing national treatment strategies for curatively resected colonic and rectal cancer. Br J Surg 2011;98:716–23.
   PubMed Web of Science ®Google Scholar
• Casado-Saenz E, Feliu J, Gomez-Espana MA, Sanchez-Gastaldo A, Garcia-Carbonero R. SEOM Clinical guidelines for the treatment of advanced colorectal cancer 2013. Clin Transl Oncol 2013;15:996–1003.
   PubMed Web of Science ®Google Scholar
• Ohlsson B, Stenram U, Tranberg KG. Resection of colorectal liver metastases: 25-year experience. World J Surg 1998;22:268–76; discussion 76–7.
   PubMed Web of Science ®Google Scholar
• de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg 2009;250:440–8.
   PubMed Web of Science ®Google Scholar
• Bretthauer M, Kalager M. Principles, effectiveness and caveats in screening for cancer. Br J Surg 2013;100:55–65.
   PubMed Web of Science ®Google Scholar
• Garborg K, Holme O, Loberg M, Kalager M, Adami HO, Bretthauer M. Current status of screening for colorectal cancer. Ann Oncol 2013;24:1963–72.
   PubMed Web of Science ®Google Scholar
• Sorbin LH, Gospodarowicz MK, Wittekind C. International Union against Cancer (UICC). TNM classification of malignant tumours. 7 edition. West Sussex, UK: Wiley-Blackwell; 2009.
   Google Scholar
• Cascinu S, Staccioli MP, Gasparini G, Giordani P, Catalano V, Ghiselli R, et al. Expression of vascular endothelial growth factor can predict event-free survival in stage II colon cancer. Clin Cancer Res 2000;6:2803–7.
   PubMed Web of Science ®Google Scholar
• Gonen M, Weiser MR. Whither TNM? Semin Oncol 2010;37:27–30.
   PubMedGoogle Scholar
• Ueno H, Mochizuki H, Akagi Y, Kusumi T, Yamada K, Ikegami M, et al. Optimal colorectal cancer staging criteria in TNM classification. J Clin Oncol 2012;30:1519–26.
   PubMed Web of Science ®Google Scholar
• Williams ST, Beart RW Jr. Staging of colorectal cancer. Semin Surg Oncol 1992;8:89–93.
   PubMedGoogle Scholar
• Hashiguchi Y, Hase K, Kotake K, Ueno H, Shinto E, Mochizuki H, et al. Evaluation of the seventh edition of the tumour, node, metastasis (TNM) classification for colon cancer in two nationwide registries of the United States and Japan. Colorectal Dis 2012;14:1065–74.
   PubMed Web of Science ®Google Scholar
• Puppa G, Sonzogni A, Colombari R, Pelosi G. TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues. Arch Pathol Lab Med 2010;134:837–52.
   PubMed Web of Science ®Google Scholar
• Nagtegaal ID, Quirke P, Schmoll HJ. Has the new TNM classification for colorectal cancer improved care? Nat Rev Clin Oncol 2012;9:119–23.
   Web of Science ®Google Scholar
• Veen T, Nedrebø BS, Stormark K, Søreide JA, Kørner H, Søreide K. Qualitative and quantitative issues of lymph nodes as prognostic factor in colon cancer. Dig Surg 2013;30:1–11.
   PubMedGoogle Scholar
• Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart AK. Revised TN categorization for colon cancer based on national survival outcomes data. J Clin Oncol 2010;28:264–71.
   PubMed Web of Science ®Google Scholar
• American Joint Committee on Cancer. Cancer staging manual. 7 edition. Chicago, IL: Springer; 2010. p 649.
   Google Scholar
• Lan YT, Yang SH, Chang SC, Liang WY, Li AF, Wang HS, et al. Analysis of the seventh edition of American Joint Committee on colon cancer staging. Int J Colorectal Dis 2012;27:657–63.
   PubMedGoogle Scholar
• Sorbin LH, Fleming ID. TNM classification of malignant tumours. New York: Wiley; 1997.
   Google Scholar
• Sorbin LH, Wittekind Ch. TNM classification of malignant tumours. New York: Wiley; 2002.
   Google Scholar
• Lorenzon L, Pilozzi E, La Torre M, Ziparo V, Ferri M. Impact and prognostic implications of colon cancers stage II sub-classification through the years. Int J Colorectal Dis 2012;27:1311–18.
   PubMedGoogle Scholar
• Snaebjornsson P, Coupe VM, Jonasson L, Meijer GA, van Grieken NC, Jonasson JG. pT4 stage II and III colon cancers carry the worst prognosis in a nationwide survival analysis. Shepherd’s local peritoneal involvement revisited. Int J Cancer 2014;135:467–78.
   PubMedGoogle Scholar
• Stewart CJ, Hillery S, Platell C, Puppa G. Assessment of serosal invasion and criteria for the classification of pathological (p) T4 staging in colorectal carcinoma: confusions, controversies and criticisms. Cancers (Basel) 2011;3:164–81.
   PubMedGoogle Scholar
• Compton C, Fenoglio-Preiser CM, Pettigrew N, Fielding LP. American joint committee on cancer prognostic factors consensus conference: colorectal working group. Cancer 2000;88:1739–57.
   PubMed Web of Science ®Google Scholar
• Oh SY, Kim YB, Paek OJ, Suh KW. Contiguous invasion per se does not affect prognosis in colon cancer. J Surg Oncol 2009;99:71–4.
   PubMedGoogle Scholar
• Compton CC. Key issues in reporting common cancer specimens: problems in pathologic staging of colon cancer. Arch Pathol Lab Med 2006;130:318–24.
   PubMed Web of Science ®Google Scholar
• Nagtegaal ID, Quirke P. Colorectal tumour deposits in the mesorectum and pericolon; a critical review. Histopathology 2007;51:141–9.
   PubMedGoogle Scholar
• Goldstein NS, Turner JR. Pericolonic tumor deposits in patients with T3N+MO colon adenocarcinomas: markers of reduced disease free survival and intra-abdominal metastases and their implications for TNM classification. Cancer 2000;88:2228–38.
   PubMedGoogle Scholar
• Wunsch K, Muller J, Jahnig H, Herrmann RA, Arnholdt HM, Markl B. Shape is not associated with the origin of pericolonic tumor deposits. Am J Clin Pathol 2010;133:388–94.
   PubMedGoogle Scholar
• Nagtegaal ID, Tot T, Jayne DG, McShane P, Nihlberg A, Marshall HC, et al. Lymph nodes, tumor deposits, and TNM: are we getting better? J Clin Oncol 2011;29:2487–92.
   PubMedGoogle Scholar
• Edge SBB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. editors. AJCC cancer staging manual. New York: Springer; 2010. pp 649.
   Google Scholar
• Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer; 2010.
   Google Scholar
• Rock JB, Washington MK, Adsay NV, Greenson JK, Montgomery EA, Robert ME, et al. Debating deposits: an interobserver variability study of lymph nodes and pericolonic tumor deposits in colonic adenocarcinoma. Arch Pathol Lab Med 2014;138:636–42.
   PubMedGoogle Scholar
• Song YX, Gao P, Wang ZN, Liang JW, Sun Z, Wang MX, et al. Can the tumor deposits be counted as metastatic lymph nodes in the UICC TNM staging system for colorectal cancer? PLoS One 2012;7:e34087.
   Google Scholar
• Puppa G. Enhanced pathologic analysis for pericolonic tumor deposits: is it worth it? Am J Clin Pathol 2010;134:1019–21.
   PubMedGoogle Scholar
• Lin Y, Chappell R, Gonen M. A systematic selection method for the development of cancer staging systems. Stat Methods Med Res 2013; [Epub ahead of print].
   Google Scholar
• Quirke P, Palmer T, Hutchins GG, West NP. Histopathological work-up of resection specimens, local excisions and biopsies in colorectal cancer. Dig Dis 2012;30:2–8.
   PubMed Web of Science ®Google Scholar
• Quirke P, Cuvelier C, Ensari A, Glimelius B, Laurberg S, Ortiz H, et al. Evidence-based medicine: the time has come to set standards for staging. J Pathol 2010;221:357–60.
   PubMed Web of Science ®Google Scholar
• Sobin LH, Compton CA, Gospodarowicz M, Greene FL, Gunderson LL, Jessup JM, et al. ’Evidence-based medicine: the time has come to set standards for staging’. Is a radical overhaul really needed? J Pathol 2010;221:361–2.
   PubMedGoogle Scholar
• Blenkinsopp WK, Stewart-Brown S, Blesovsky L, Kearney G, Fielding LP. Histopathology reporting in large bowel cancer. J Clin Pathol 1981;34:509–13.
   PubMed Web of Science ®Google Scholar
• Boyle P, Levin B. World cancer report. Lyon: IARC Press; 2008.
   Google Scholar
• Benedix F, Kuester D, Meyer F, Lippert H. [Influence of mucinous and signet-ring cell differentiation on epidemiological, histological, molecular biological features, and outcome in patients with colorectal carcinoma]. Zentralbl Chir 2013;138:427–33.
   PubMedGoogle Scholar
• Nitsche U, Zimmermann A, Spath C, Muller T, Maak M, Schuster T, et al. Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis. Ann Surg 2013;258:775–83.
   PubMed Web of Science ®Google Scholar
• Sung CO, Seo JW, Kim KM, Do IG, Kim SW, Park CK. Clinical significance of signet-ring cells in colorectal mucinous adenocarcinoma. Mod Pathol 2008;21:1533–41.
   PubMed Web of Science ®Google Scholar
• Lee HJ, Eom DW, Kang GH, Han SH, Cheon GJ, Oh HS, et al. Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells. Mod Pathol 2013;26:1123–31.
   PubMed Web of Science ®Google Scholar
• Lino-Silva LS, Salcedo-Hernandez RA, Caro-Sanchez CH. Colonic micropapillary carcinoma, a recently recognized subtype associated with histological adverse factors: clinicopathological analysis of 15 cases. Colorectal Dis 2012;14:e567–72.
   PubMedGoogle Scholar
• Dukes C. Histological grading of rectal cancer: (section of pathology). Proc R Soc Med 1937;30:371–6.
   PubMedGoogle Scholar
• Grinnell RS. The grading and prognosis of carcinoma of the colon and rectum. Ann Surg 1939;109:500–33.
   PubMedGoogle Scholar
• Ueno H, Kajiwara Y, Shimazaki H, Shinto E, Hashiguchi Y, Nakanishi K, et al. New criteria for histologic grading of colorectal cancer. Am J Surg Pathol 2012;36:193–201.
   PubMed Web of Science ®Google Scholar
• Greene FL, Stewart AK, Norton HJ. A new TNM staging strategy for node-positive (stage III) colon cancer: an analysis of 50,042 patients. Ann Surg 2002;236:416–21; discussion 21.
   PubMed Web of Science ®Google Scholar
• Freedman LS, Macaskill P, Smith AN. Multivariate analysis of prognostic factors for operable rectal cancer. Lancet 1984;2:733–6.
   PubMed Web of Science ®Google Scholar
• Thomas GD, Dixon MF, Smeeton NC, Williams NS. Observer variation in the histological grading of rectal carcinoma. J Clin Pathol 1983;36:385–91.
   PubMed Web of Science ®Google Scholar
• Quirke P, Morris E. Reporting colorectal cancer. Histopathology 2007;50:103–12.
   PubMed Web of Science ®Google Scholar
• Liang P, Nakada I, Hong JW, Tabuchi T, Motohashi G, Takemura A, et al. Prognostic significance of immunohistochemically detected blood and lymphatic vessel invasion in colorectal carcinoma: its impact on prognosis. Ann Surg Oncol 2007;14:470–7.
   PubMed Web of Science ®Google Scholar
• Bentzen SM, Balslev I, Pedersen M, Teglbjaerg PS, Hanberg-Sorensen F, Bone J, et al. Time to loco-regional recurrence after resection of Dukes’ B and C colorectal cancer with or without adjuvant postoperative radiotherapy. A multivariate regression analysis. Br J Cancer 1992;65:102–7.
   PubMed Web of Science ®Google Scholar
• Puppa G, Caneva A, Colombari R. Venous invasion detection in colorectal cancer: which approach, which technique? J Clin Pathol 2009;62:102–3.
   PubMedGoogle Scholar
• Sternberg A, Amar M, Alfici R, Groisman G. Conclusions from a study of venous invasion in stage IV colorectal adenocarcinoma. J Clin Pathol 2002;55:17–21.
   PubMed Web of Science ®Google Scholar
• Ueno H, Price AB, Wilkinson KH, Jass JR, Mochizuki H, Talbot IC. A new prognostic staging system for rectal cancer. Ann Surg 2004;240:832–9.
   PubMedGoogle Scholar
• Lugli A, Karamitopoulou E, Zlobec I. Tumour budding: a promising parameter in colorectal cancer. Br J Cancer 2012;106:1713–17.
   PubMedGoogle Scholar
• Jass JR, O’Brien J, Riddell RH, Snover DC. Recommendations for the reporting of surgically resected specimens of colorectal carcinoma: Association of Directors of Anatomic and Surgical Pathology. Am J Clin Pathol 2008;129:13–23.
   PubMedGoogle Scholar
• Hase K, Shatney C, Johnson D, Trollope M, Vierra M. Prognostic value of tumor "budding" in patients with colorectal cancer. Dis Colon Rectum 1993;36:627–35.
   PubMed Web of Science ®Google Scholar
• Kazama S, Watanabe T, Ajioka Y, Kanazawa T, Nagawa H. Tumour budding at the deepest invasive margin correlates with lymph node metastasis in submucosal colorectal cancer detected by anticytokeratin antibody CAM5.2. Br J Cancer 2006;94:293–8.
   PubMed Web of Science ®Google Scholar
• Nakamura T, Mitomi H, Kikuchi S, Ohtani Y, Sato K. Evaluation of the usefulness of tumor budding on the prediction of metastasis to the lung and liver after curative excision of colorectal cancer. Hepatogastroenterology 2005;52:1432–5.
   PubMed Web of Science ®Google Scholar
• Wang LM, Kevans D, Mulcahy H, O’Sullivan J, Fennelly D, Hyland J, et al. Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer. Am J Surg Pathol 2009;33:134–41.
   PubMed Web of Science ®Google Scholar
• Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 2009;30:1073–81.
   PubMed Web of Science ®Google Scholar
• Di Caro G, Bergomas F, Grizzi F, Doni A, Bianchi P, Malesci A, et al. Occurrence of tertiary lymphoid tissue is associated with T-cell infiltration and predicts better prognosis in early-stage colorectal cancers. Clin Cancer Res 2014;20:2147–58.
   PubMed Web of Science ®Google Scholar
• Roxburgh CS, McMillan DC. The role of the in situ local inflammatory response in predicting recurrence and survival in patients with primary operable colorectal cancer. Cancer Treat Rev 2012;38:451–66.
   PubMed Web of Science ®Google Scholar
• Curtis NJ, Primrose JN, Thomas GJ, Mirnezami AH, Ottensmeier CH. The adaptive immune response to colorectal cancer: from the laboratory to clinical practice. Eur J Surg Oncol 2012;38:889–96.
   PubMedGoogle Scholar
• Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006;313:1960–4.
   PubMed Web of Science ®Google Scholar
• Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 2011;29:610–18.
   PubMed Web of Science ®Google Scholar
• Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454:436–44.
   PubMed Web of Science ®Google Scholar
• Chaput N, Svrcek M, Auperin A, Locher C, Drusch F, Malka D, et al. Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III colorectal cancer. Br J Cancer 2013;109:1013–22.
   PubMed Web of Science ®Google Scholar
• Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003;4:330–6.
   PubMed Web of Science ®Google Scholar
• Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003;9:606–12.
   PubMed Web of Science ®Google Scholar
• Loddenkemper C, Schernus M, Noutsias M, Stein H, Thiel E, Nagorsen D. In situ analysis of FOXP3+ regulatory T cells in human colorectal cancer. J Transl Med 2006;4:52.
   PubMedGoogle Scholar
• Kim M, Grimmig T, Grimm M, Lazariotou M, Meier E, Rosenwald A, et al. Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer. PLoS One 2013;8:e53630.
   PubMed Web of Science ®Google Scholar
• Galon J, Franck P, Marincola FM, Angell HK, Thurin M, Lugli A, et al. Cancer classification using the Immunoscore: a worldwide task force. J Transl Med 2012;10:205.
   PubMed Web of Science ®Google Scholar
• Pages F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 2009;27:5944–51.
   PubMed Web of Science ®Google Scholar
• Anitei MG, Zeitoun G, Mlecnik B, Marliot F, Haicheur N, Todosi AM, et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer. Clin Cancer Res 2014;20:1891–9.
   PubMed Web of Science ®Google Scholar
• Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 2014;232:199–209.
   PubMed Web of Science ®Google Scholar
• Huijbers A, Tollenaar RA, v Pelt GW, Zeestraten EC, Dutton S, McConkey CC, et al. The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol 2013;24:179–85.
   PubMed Web of Science ®Google Scholar
• Perez-Villamil B, Romera-Lopez A, Hernandez-Prieto S, Lopez-Campos G, Calles A, Lopez-Asenjo JA, et al. Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior. BMC Cancer 2012;12:260.
   PubMed Web of Science ®Google Scholar
• Wikberg ML, Edin S, Lundberg IV, Van Guelpen B, Dahlin AM, Rutegard J, et al. High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumour Biol 2013;34:1013–20.
   PubMedGoogle Scholar
• Saadi A, Shannon NB, Lao-Sirieix P, O’Donovan M, Walker E, Clemons NJ, et al. Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers. Proc Natl Acad Sci USA 2010;107:2177–82.
   PubMed Web of Science ®Google Scholar
• Inafuku Y, Furuhata T, Tayama M, Okita K, Nishidate T, Mizuguchi T, et al. Matrix metalloproteinase-2 expression in stromal tissues is a consistent prognostic factor in stage II colon cancer. Cancer Sci 2009;100:852–8.
   PubMedGoogle Scholar
• Henry LR, Lee HO, Lee JS, Klein-Szanto A, Watts P, Ross EA, et al. Clinical implications of fibroblast activation protein in patients with colon cancer. Clin Cancer Res 2007;13:1736–41.
   PubMed Web of Science ®Google Scholar
• He X, Chen Z, Jia M, Zhao X. Downregulated e-cadherin expression indicates worse prognosis in asian patients with colorectal cancer: evidence from meta-analysis. PLoS One 2013;8:e70858.
   Google Scholar
• Roepman P, Schlicker A, Tabernero J, Majewski I, Tian S, Moreno V, et al. Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition. Int J Cancer 2014;134:552–62.
   PubMed Web of Science ®Google Scholar
• De Sousa EMF, Wang X, Jansen M, Fessler E, Trinh A, de Rooij LP, et al. Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 2013;19:614–18.
   PubMed Web of Science ®Google Scholar
• Peddareddigari VG, Wang D, Dubois RN. The tumor microenvironment in colorectal carcinogenesis. Cancer Microenviron 2010;3:149–66.
   PubMedGoogle Scholar
• Zhang QW, Liu L, Gong CY, Shi HS, Zeng YH, Wang XZ, et al. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS One 2012;7:e50946.
   PubMed Web of Science ®Google Scholar
• Cronier L, Crespin S, Strale PO, Defamie N, Mesnil M. Gap junctions and cancer: new functions for an old story. Antioxid Redox Signal 2009;11:323–38.
   PubMed Web of Science ®Google Scholar
• Han Y, Zhang PJ, Chen T, Yum SW, Pasha T, Furth EE. Connexin43 expression increases in the epithelium and stroma along the colonic neoplastic progression pathway: implications for its oncogenic role. Gastroenterol Res Pract 2011;2011:561719.
   PubMedGoogle Scholar
• Kerbel RS. Tumor angiogenesis. N Engl J Med 2008;358:2039–49.
   PubMed Web of Science ®Google Scholar
• Gaya A, Tse V. A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev 2012;38:484–93.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646–74.
   PubMed Web of Science ®Google Scholar
• Mathonnet M, Perraud A, Christou N, Akil H, Melin C, Battu S, et al. Hallmarks in colorectal cancer: angiogenesis and cancer stem-like cells. World J Gastroenterol 2014;20:4189–96.
   PubMed Web of Science ®Google Scholar
• Choi HJ, Hyun MS, Jung GJ, Kim SS, Hong SH. Tumor angiogenesis as a prognostic predictor in colorectal carcinoma with special reference to mode of metastasis and recurrence. Oncology 1998;55:575–81.
   PubMed Web of Science ®Google Scholar
• Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer 2006;94:1823–32.
   PubMed Web of Science ®Google Scholar
• Lee JC, Chow NH, Wang ST, Huang SM. Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer 2000;36:748–53.
   PubMed Web of Science ®Google Scholar
• Kaio E, Tanaka S, Kitadai Y, Sumii M, Yoshihara M, Haruma K, et al. Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology 2003;64:61–73.
   PubMedGoogle Scholar
• Tayama M, Furuhata T, Inafuku Y, Okita K, Nishidate T, Mizuguchi T, et al. Vascular endothelial growth factor 165b expression in stromal cells and colorectal cancer. World J Gastroenterol 2011;17:4867–74.
   PubMedGoogle Scholar
• Kazama S, Watanabe T, Kanazawa T, Hatano K, Nagawa H. Vascular endothelial growth factor-C (VEGF-C) is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer. Hepatogastroenterology 2007;54:71–6.
   PubMedGoogle Scholar
• Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med 1991;324:1–8.
   PubMed Web of Science ®Google Scholar
• Hansen TF, Sorensen FB, Spindler KL, Olsen DA, Andersen RF, Lindebjerg J, et al. Microvessel density and the association with single nucleotide polymorphisms of the vascular endothelial growth factor receptor 2 in patients with colorectal cancer. Virchows Arch 2010;456:251–60.
   PubMedGoogle Scholar
• Lindmark G, Gerdin B, Sundberg C, Pahlman L, Bergstrom R, Glimelius B. Prognostic significance of the microvascular count in colorectal cancer. J Clin Oncol 1996;14:461–6.
   PubMed Web of Science ®Google Scholar
• Sheehan KM, Steele C, Sheahan K, O’Grady A, Leader MB, Murray FE, et al. Association between cyclooxygenase-2-expressing macrophages, ulceration and microvessel density in colorectal cancer. Histopathology 2005;46:287–95.
   PubMed Web of Science ®Google Scholar
• Rajaganeshan R, Prasad R, Guillou PJ, Chalmers CR, Scott N, Sarkar R, et al. The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases. Br J Cancer 2007;96:1112–17.
   Google Scholar
• Pietra N, Sarli L, Caruana P, Cabras A, Costi R, Gobbi S, et al. Is tumour angiogenesis a prognostic factor in patients with colorectal cancer and no involved nodes? Eur J Surg 2000;166:552–6.
   PubMedGoogle Scholar
• Uribarrena AR, Ortego J, Fuentes J, Raventos N, Parra P, Uribarrena ER. Prognostic value of microvascular density in dukes a and B (t1-t4, n0, m0) colorectal carcinomas. Gastroenterol Res Pract 2009;2009:679830.
   PubMedGoogle Scholar
• Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, et al. Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 2002;38:1564–79.
   PubMed Web of Science ®Google Scholar
• Mallett S, Timmer A, Sauerbrei W, Altman DG. Reporting of prognostic studies of tumour markers: a review of published articles in relation to REMARK guidelines. Br J Cancer 2010;102:173–80.
   PubMed Web of Science ®Google Scholar
• Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. Toward complete and accurate reporting of studies of diagnostic accuracy. The STARD initiative. Am J Clin Pathol 2003;119:18–22.
   PubMed Web of Science ®Google Scholar