Abstract
Lymphatic invasion (LI) and venous invasion (VI) are regarded as important risk factors of nodal disease in early-stage colorectal cancer (CRC) but with variable reporting and poor distinction of these parameters in previous studies. This study examines the application of a double immunohistochemistry (D-IHC) method to help detect and distinguish LI and VI, in comparison with haematoxylin and eosin (H&E) staining, in a clinical series of cases of stage pT1 CRC. The aims were to demonstrate feasibility of this methodology in routine practice and compare rates of LI and VI reporting with and without D-IHC application. D-IHC utilising CAM5.2 with the endothelial marker CD34 and with the specific lymphatic endothelial marker D2-40 was performed on parallel sections from single representative paraffin tissue blocks in 28 cases of stage pT1 CRC from routine clinical practice. D-IHC significantly increased rates of both LI and VI reporting, from 14.3 to 35.7 % and from 14.3 to 28.6 %, respectively. The D-IHC methodology described is technically feasible in routine practice and potentially offers a more sensitive and robust assay for detection and distinction of LI and VI in early CRC pathology reporting. The reproducibility and clinical significance of enhanced LI and VI detection by this method and the relative importance of LI and VI in this clinical setting require further study.
Similar content being viewed by others
References
Ellul P, Fogden E, Simpson CL, Nickerson CLR, McKaig BC, Swarbrick ET, Veitch AM (2010) Downstaging of colorectal cancer by the national bowel cancer screening programme in England: first round data from the first centre. Color Dis 12:420–422
Williams JG, Pullan RD, Hill J, Horgan PG, Salmo E, Buchanan GN, Rasheed S, McGee SG, Haboubi N (2013) Management of the malignant colorectal polyp: ACPGBI position statement. Color Dis 15(Suppl 2):1–38
Winde G, Nottberg H, Keller R, Schmid KW, Bünte H (1996) Surgical cure for early rectal carcinomas (T1). Transanal endoscopic microsurgery vs. anterior resection. Dis Colon Rectum 39:969–976
Langer C, Liersch T, Süss M, Siemer A, Markus P, Ghadimi BM, Füzesi L, Becker H (2003) Surgical cure for early rectal carcinoma and large adenoma: transanal endoscopic microsurgery (using ultrasound or electrosurgery) compared to conventional local and radical resection. Int J Color Dis 18:222–229
Wu Y, Wu Y-Y, Li S, Zhu B-S, Zhao K, Yang X-D, Xing CG (2011) TEM and conventional rectal surgery for T1 rectal cancer: a meta-analysis. Hepato-Gastroenterology 58:364–368
Mellgren A, Sirivongs P, Rothenberger DA, Madoff RD, García-Aguilar J (2000) Is local excision adequate therapy for early rectal cancer? Dis Colon Rectum 43:1064–1071, Discussion 1071–4
Tanaka S, Haruma K, Teixeira CR, Tatsuta S, Ohtsu N, Hiraga Y, Yoshihara M, Sumii K, Kajiyama G, Shimamoto F (1995) Endoscopic treatment of submucosal invasive colorectal carcinoma with special reference to risk factors for lymph node metastasis. J Gastroenterol 30:710–717
Kobayashi H, Mochizuki H, Morita T et al (2011) Characteristics of recurrence after curative resection for T1 colorectal cancer: Japanese multicenter study. J Gastroenterol 46:203–211
Coverlizza S, Risio M, Ferrari A, Fenoglio-Preiser CM, Rossini FP (1989) Colorectal adenomas containing invasive carcinoma. Pathologic assessment of lymph node metastatic potential. Cancer 64:1937–1947
Kitamura K, Taniguchi H, Yamaguchi T, Sawai K, Takahashi T (1997) Clinical outcome of surgical treatment for invasive early colorectal cancer in Japan. Hepato-Gastroenterology 44:108–115
Son HJ, Song SY, Lee WY, Yang SS, Park SH, Yang MH, Yoon SH, Chun HK (2008) Characteristics of early colorectal carcinoma with lymph node metastatic disease. Hepato-Gastroenterology 55:1293–1297
Cooper HS (1983) Surgical pathology of endoscopically removed malignant polyps of the colon and rectum. Am J Surg Pathol 7:613–623
Morson BC, Whiteway JE, Jones EA, Macrae FA, Williams CB (1984) Histopathology and prognosis of malignant colorectal polyps treated by endoscopic polypectomy. Gut 25:437–444
Hassan C, Zullo A, Risio M, Rossini FP, Morini S (2005) Histologic risk factors and clinical outcome in colorectal malignant polyp: a pooled-data analysis. Dis Colon Rectum 48:1588–1596
Vieth M, Quirke P, Lambert R, von Karsa L, Risio M (2011) Annex to Quirke et al. quality assurance in pathology in colorectal cancer screening and diagnosis: annotations of colorectal lesions. Virchows Arch 458:21–30
Haggitt RC, Glotzbach RE, Soffer EE, Wruble LD (1985) Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. Gastroenterology 89:328–336
Kikuchi R, Takano M, Takagi K, Fujimoto N, Nozaki R, Fujiyoshi T, Uchida Y (1995) Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines. Dis Colon Rectum 38:1286–1295
Ueno H, Mochizuki H, Hashiguchi Y et al (2004) Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 127:385–394
Egashira Y, Yoshida T, Hirata I, Hamamoto N, Akutagawa H, Takeshita A, Noda N, Kurisu Y, Shibayama Y (2004) Analysis of pathological risk factors for lymph node metastasis of submucosal invasive colon cancer. Mod Pathol 17:503–511
Ishikawa Y, Akishima-Fukasawa Y, Ito K, Akasaka Y, Yokoo T, Ishii T (2008) Histopathologic determinants of regional lymph node metastasis in early colorectal cancer. Cancer 112:924–933
Wang H-S, Liang W-Y, Lin T-C, Chen W-S, Jiang J-K, Yang S-H, Chang S-C, Lin J-K (2005) Curative resection of T1 colorectal carcinoma: risk of lymph node metastasis and long-term prognosis. Dis Colon Rectum 48:1182–1192
Bosch SL, Teerenstra S, de Wilt JHW, Cunningham C, Nagtegaal ID (2013) Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of risk factors providing rationale for therapy decisions. Endoscopy 45:827–841
Beaton C, Twine CP, Williams GL, Radcliffe AG (2013) Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer. Color Dis 15:788–797
Alexander-Sefre F, Singh N, Ayhan A, Salveson HB, Wilbanks G, Jacobs IJ (2003) Detection of tumour lymphovascular space invasion using dual cytokeratin and CD31 immunohistochemistry. J Clin Pathol 56:786–788
Kahn HJ, Marks A (2002) A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Investig 82:1255–1257
Tsuruta O, Tsuji Y, Kawano H et al (2000) Indication for endoscopic resection of submucosal colorectal carcinoma: special reference to lymph node metastasis. Diagn Ther Endosc 6:101–109
Muller S, Chesner IM, Egan MJ, Rowlands DC, Collard MJ, Swarbrick ET, Newman J (1989) Significance of venous and lymphatic invasion in malignant polyps of the colon and rectum. Gut 30:1385–1391
Ishii M, Ota M, Saito S, Kinugasa Y, Akamoto S, Ito I (2009) Lymphatic vessel invasion detected by monoclonal antibody D2-40 as a predictor of lymph node metastasis in T1 colorectal cancer. Int J Color Dis 24:1069–1074
Suzuki A, Togashi K, Nokubi M, Koinuma K, Miyakura Y, Horie H, Lefor AT, Yasuda Y (2009) Evaluation of venous invasion by Elastica van Gieson stain and tumor budding predicts local and distant metastases in patients with T1 stage colorectal cancer. Am J Surg Pathol 33:1601–1607
Saad RS, Kordunsky L, Liu YL, Denning KL, Kandil HA, Silverman JF (2006) Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol 19:1317–1323
Walgenbach-Bruenagel G, Tolba RH, Varnai AD, Bollmann M, Hirner A, Walgenbach KJ (2006) Detection of lymphatic invasion in early stage primary colorectal cancer with the monoclonal antibody D2-40. Eur Surg Res 38:438–444
Barresi V, Reggiani Bonetti L, Vitarelli E, Di Gregorio C, Ponz de Leon M, Barresi G (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
Harris EI, Lewin DN, Wang HL, Lauwers GY, Srivastava A, Shyr Y, Shakhtour B, Revetta F, Washington MK (2008) Lymphovascular invasion in colorectal cancer: an interobserver variability study. Am J Surg Pathol 32:1816–1821
Quirke P, Risio M, Lambert R, von Karsa L, Vieth M (2011) Quality assurance in pathology in colorectal cancer screening and diagnosis—European recommendations. Virchows Arch 458:1–19
Volk EE, Goldblum JR, Petras RE, Carey WD, Fazio VW (1995) Management and outcome of patients with invasive carcinoma arising in colorectal polyps. Gastroenterology 109:1801–1807
Geraghty JM, Williams CB, Talbot IC (1991) Malignant colorectal polyps: venous invasion and successful treatment by endoscopic polypectomy. Gut 32:774–778
Williams CB, Geraghty JM (1990) The malignant polyp—when to operate: the St. Mark’s experience. Can J Gastroenterol 4:549–553
Acknowledgments
M.B. Loughrey was responsible for the study design, performed the research and analysed the data. A.J. Ervine performed the research and analysed the data. H.A. McBride optimised and performed the immunohistochemistry. All authors contributed to manuscript writing, editing and proof reading.
Conflict of interest
The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ervine, A.J., McBride, H.A., Kelly, P.J. et al. Double immunohistochemistry enhances detection of lymphatic and venous invasion in early-stage colorectal cancer. Virchows Arch 467, 265–271 (2015). https://doi.org/10.1007/s00428-015-1792-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-015-1792-x