Skip to main content

Advertisement

SpringerLink
Log in

Increased density and diameter of lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

To determine whether lymphangiogenesis was associated with the development of colorectal carcinoma and whether the mean maximal diameter of lymphatic microvessels (LMMMD) or lymphatic microvessel density (LMVD) is associated with lymph node metastasis in early stage invasive colorectal carcinoma (T1 carcinoma), we used immunohistochemical staining with podoplanin to measure LMMMD and LMVD in intratumoral (LMMMDit, LMVDit) and peritumoral areas (LMMMDpt, LMVDpt) of T1 carcinomas (n=87). By comparing the LMMMD and LMVD in normal large intestine (n=10), adenoma (n=15), and Tis carcinoma (n=15), we found out that the LMVDpt in T1 carcinoma with lymphatic vessel invasion (LVI) was significantly high (P<0.001), and there was a significant decrease in LMMMDpt in T1 carcinoma (P=0.031). Both LMMMDpt and LMVDpt were significantly increased in the T1 carcinomas, with LVI compared with the T1 carcinomas without LVI (P=0.018, P=0.003). Multivariate analysis revealed that LVI and combined greater LMMMDpt and greater LMVDpt were associated with lymph node metastases (P=0.005, P=0.036). These results indicate that lymphangiogenesis might be induced in the surrounding tumor areas of the T1 colorectal carcinoma with LVI; thus, evaluation of the diameter and density of lymphatic microvessels is important in T1 colorectal carcinoma to predict lymph node metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig 3

Similar content being viewed by others

References

  1. Birner P, Obermair A, Schindl M, Kowalski H, Breitenecker G, Oberhuber G (2001) Selective immunohistochemical staining of blood and lymphatic vessels reveal independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancer. Clin Cancer Res 7:93–97

    PubMed  CAS  Google Scholar 

  2. Boardman KC, Swartz MA (2003) Interstitial flow as a guide for lymphangiogenesis. Circ Res 92:801–808

    Article  PubMed  CAS  Google Scholar 

  3. Bonfil RD, Bustuoabad OD, Ruggiero RA, Meiss RP, Pasqualini CD (1988) Tumor necrosis can facilitate the appearance of metastases. Clin Exp Metastasis 6:121–129

    Article  PubMed  CAS  Google Scholar 

  4. Breiteneder-Geleff S, Soleiman A, Kowalski H et al (1999) Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 154:385–394

    PubMed  CAS  Google Scholar 

  5. Gerli R, Ibba L, Fruscheli C (1991) Ultrastructural cytochemistry of anchoring filaments of human lymphatic capillaries and their relation to elastic fibers. Lymphology 24:105–112

    PubMed  CAS  Google Scholar 

  6. Hewitt RE, Powe DG, Carter GI, Turner DR (1993) Desmoplasia and its relevance to colorectal tumor invasion. Int J Cancer 53:62–69

    Article  PubMed  CAS  Google Scholar 

  7. He YL, Karpanen T, Alitalo K (2004) Role of lymphangiogenic factors in tumor metastasis. Biochim Biophys Acta 1654:3–12

    PubMed  CAS  Google Scholar 

  8. Kozaki K, Koshikawa K, Tatematsu Y et al (2001) Multi-faceted analyses of a highly metastatic human lung cancer cell line NCI-H460-LNM35 suggest mimicry of inflammatory cells in metastasis. Oncogene 20:4228–4234

    Article  PubMed  CAS  Google Scholar 

  9. Kudo S (1993) Endoscopic mucosal resection of flat and depressed type of early colorectal cancer. Endoscopy 25:455–461

    Article  PubMed  CAS  Google Scholar 

  10. Kudo S, Tamegai Y, Yamano H, Imai Y, Kogure E, Kashida H (2001) Endoscopic mucosal resection of the colon: the Japanese technique. Gastrointest Endosc Clin N Am 11:519–535

    PubMed  CAS  Google Scholar 

  11. Leak LV, Burke JF (1968) Electron microscopic study of lymphatic capillaries in the removal of connective tissue fluids and particulate substances. Lymphology 1:39–52

    PubMed  CAS  Google Scholar 

  12. Leu AJ, Berk DA, Lymboussaki A, Alitalo K, Jain RK (2000) Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res 60:4324–4327

    PubMed  CAS  Google Scholar 

  13. Liang P, Hong JW, Ubukata H et al (2005) Myofibroblasts correlates with lymphatic microvessel density and lymph node metastasis in early-stage invasive colorectal carcinoma. Anticancer Res 25:2705–2712

    PubMed  Google Scholar 

  14. Mandriota SJ, Jussila L, Jeltsch M et al (2001) Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 20:672–682

    Article  PubMed  CAS  Google Scholar 

  15. Nakada I, Tasaki T, Ubukata H et al (1998) Desmoplastic response in biopsy specimens of early colorectal carcinoma is predictive of deep submucosal invasion. Dis Colon Rectum 41:896–900

    Article  PubMed  CAS  Google Scholar 

  16. Padera TP, Kadambi A, Tomaso E et al (2002) Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 296:1883–1886

    Article  PubMed  CAS  Google Scholar 

  17. Repici A, Tricerri R (2004) Endoscopic polypectomy: techniques, complications and follow-up. Tech Coloproctol 8:283–290

    Article  Google Scholar 

  18. Roche WD, Norris HJ (1975) Microinvasive carcinoma of the cervix. The significance of lymphatic invasion and confluent patterns of stromal growth. Cancer 36:180–186

    Article  PubMed  CAS  Google Scholar 

  19. Schoppmann SF, Schindl M, Breiteneder-Geleff S et al (2001) Inflammatory stromal reaction correlates with lymphatic microvessel density in early-stage cervical cancer. Anticancer Res 21:3419–3423

    PubMed  CAS  Google Scholar 

  20. Schoppmann SF, Bayer G, Aumayr K, Taucher S, Geleff S, Ruda (2004) Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer. Ann Surg 240:306–312

    Article  PubMed  Google Scholar 

  21. Shields JD, Borsetti M, Rigby H et al (2004) Lymphatic density and metastatic spread in human malignant melanoma. Br J Cancer 90(3):693–700 (Feb 9)

    Article  PubMed  CAS  Google Scholar 

  22. Skobe M, Hawighorst T, Jackson DG et al (2001) Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med 7(2):192–198

    Article  PubMed  CAS  Google Scholar 

  23. Stacker SA, Caesar C, Baldwin ME et al (2001) VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med 7:186–191

    Article  PubMed  CAS  Google Scholar 

  24. Stacker SA, Baldwin ME, Achen MG (2002) The role of tumor lymphangiogenesis in metastatic spread. FASEB J 16:922–934

    Article  PubMed  CAS  Google Scholar 

  25. Straume O, Jackson DG, Akslen LA (2003) Independent prognostic impact of lymphatic vessel density and presence of low-grade lymphangiogenesis in cutaneous melanoma. Clin Cancer Res 9:250–256

    PubMed  CAS  Google Scholar 

  26. Valencak J, Heere-Ress E, Kopp T, Schoppmann SF, Kittler H, Pehamberger H (2004) Selective immunohistochemical staining shows significant prognostic influence of lymphatic and blood vessels in patients with malignant melanoma. Eur J Cancer 40:358–364

    Article  PubMed  CAS  Google Scholar 

  27. Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 324:1–8

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Mr. Tsutomu Kohda for technical assistance and Prof. J. Patrick Barron of the International Medical Communications Center of Tokyo Medical University for his review of this manuscript. This work was supported by the Tokyo Medical University Cancer Foundation (200409).

Author information

Authors and Affiliations

  1. Fourth Department of Surgery, Tokyo Medical University, Kasumigaura Hospital, 3-20-1 Chuo, Ami, Inashiki, Ibaraki, 300-0395, Japan

    Pin Liang, Hideyuki Ubukata, Huan-Ran Liu, Yoshinori Watanabe, Motonobu Katano, Gyo Motohashi, Teruhiko Kasuga, Ichiro Nakada & Takafumi Tabuchi

  2. Department of Pathology, Tokyo Medical University, Kasumigaura Hospital, Ibaraki, 300-0395, Japan

    Jian-Wei Hong

Authors
  1. Pin Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian-Wei Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideyuki Ubukata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huan-Ran Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshinori Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Motonobu Katano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gyo Motohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Teruhiko Kasuga
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ichiro Nakada
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takafumi Tabuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pin Liang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liang, P., Hong, JW., Ubukata, H. et al. Increased density and diameter of lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma. Virchows Arch 448, 570–575 (2006). https://doi.org/10.1007/s00428-006-0166-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-006-0166-9

Keywords

Search

Navigation