Skip to main content

Advertisement

SpringerLink
Log in

Clinicopathological Significance of Tumor Lymphatic Vessel Density in Head and Neck Squamous Cell Carcinoma

  • Original Article
  • Published:
Indian Journal of Otolaryngology and Head & Neck Surgery Aims and scope Submit manuscript

Abstract

Various studies have demonstrated that the lymphatic system is the additional route for solid tumor metastasis. Lymph nodes metastasis in Head and neck squamous cell carcinoma (HNSCC) is a major prognostic indicator for disease progression and a guide for therapeutic strategies. We conducted a study to compare intratumoral (IT) and peritumoral (PT) lymphatic vessel density (LVD) in HNSCC using lymphatic marker D2-40 and its correlation with lymph node metastasis, histological grading and other clinicopathological parameters. Fifty specimen of HNSCC with modified radical neck dissection tissue were included in the study group. Tissue from tumor, peritumoral tissue, tumor margin and all the lymph nodes were processed for paraffin wax blocks and histopathological diagnosis. Immunohistochemical profile of lymphatic vessels in intratumoral and peritumoral tissue was assessed by subjecting one section each from the tumor and peritumoral tissue to D2-40 immunostain. To determine LVD, four fields with the highest LVD (hot spots) were identified. The mean values were calculated by taking an average of all the measurements. The comparison of LVD between peritumoral and intratumoral area revealed significantly higher PT-LVD (P = 0.001). No significant association was seen between LVD, IT-LVD and PT-LVD and different age groups, gender, site of tumor, risk factors, size of tumor, tumor inflammation, pushing/infiltrating margin and stage of tumors. Significantly higher LVD, IT-LVD and PT-LVD was seen in association with lymph node metastasis. Both high intratumoral and peritumoral LVD were found significantly associated with the presence of lymph node metastasis, however lymphatic vessels were found to be significantly more numerous and larger in peritumoral areas as compared to intratumoral lymphatics. The specificity of D2-40 as a lymphatic endothelial marker was also confirmed. The results of our study support the possibility of using the determination of tumor lymphangiogenesis to identify patients of HNSCC who are at risk of developing the lymph node metastasis.

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
Fig. 4

Similar content being viewed by others

References

  1. Siddiqui MS, Chandra R, Aziz A, Suman S (2012) Epidemiology and histopathological spectrum of head and neck cancers in bihar, a state of eastern India. Asian Pac J Cancer Prev 13:3949–3953

    Article  PubMed  Google Scholar 

  2. Trivedi NP, Kekatpure VD, Trivedi NN, Kuriakose MA (2012) Head and neck cancer in India: Need to formulate uniform national treatment guideline? Indian J Cancer 49:6–10

    Article  CAS  PubMed  Google Scholar 

  3. Mehrotra R, Singh M, Gupta RK, Singh M, Kapoor AK (2005) Trends of prevalence and pathological spectrum of head and neck cancers in North India. Indian J Cancer 42:89–93

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Pepper MS (2001) Lymphangiogenesis and tumor metastasis: Myth or reality? Clin Cancer Res 7:462–468

    CAS  PubMed  Google Scholar 

  6. Tobler NE, Detmar M (2006) Tumor and lymph node lymphangiogenesis-impact on cancer metastasis. J Leukoc Biol 80:691–696

    Article  CAS  PubMed  Google Scholar 

  7. Mumprecht V, Detmar M (2009) Lymphangiogenesis and cancer metastasis. J Cell Mol Med 13:1405–1416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Van der Auwera I, Cao Y, Tille JC, Pepper MS, Jackson DG, Fox SB et al (2006) First international consensus on the methodology of lymphangiogenesis quantification in solid human tumors. Br J Cancer 95:1611–1625

    Article  PubMed  PubMed Central  Google Scholar 

  9. Christiansen A, Detma M (2011) Lymphangiogenesis and cancer. Genes Cancer 2:1146–1158

    Article  PubMed  PubMed Central  Google Scholar 

  10. Achen MG, Mann GB, Stacker SA (2006) Targeting lymphangiogenesis to prevent tumor metastasis. Br J Cancer 94:1355–1360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Stacker SA, Achen MG, Jussila L, Baldwin ME, Alitalo K (2002) Lymphangiogenesis and cancer metastasis. Nat Rev Cancer 2:573–583

    Article  CAS  PubMed  Google Scholar 

  12. Sundar SS, Ganesan TS (2007) Role of lymphangiogenesis in cancer. J Clin Oncol 25:4298–4307

    Article  CAS  PubMed  Google Scholar 

  13. Fukunaga M (2005) Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumors. Histopathology 46:396–402

    Article  CAS  PubMed  Google Scholar 

  14. Bancroft JD, Layton C (2012) The hematoxylins and eosin. In: Suvarna SK, Layton C, Bancroft JD (eds) Theory and practice of histological techniques, 7th edn. Churchill Livingstone, New York, pp 173–186

    Google Scholar 

  15. Akhter M, Hossain S, Rahman QB, Molla MR (2011) A study on histological grading of oral squamous cell carcinoma and its co-relationship with regional metastasis. J Oral Maxillofac Pathol 15:168–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Slootweg PJ (2005) Complex head and neck specimens and neck dissections. How to handle them. ACP Best Practice No. 182. J Clin Pathol 58:243–248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jackson P, Blythe D (2012) Immunohistochemical techniques. In: Suvarna SK, Layton C, Bancroft JD (eds) Theory and practice of histological techniques, 7th edn. Churchill Livingstone, New York, pp 381–426

    Google Scholar 

  18. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96

    Article  PubMed  Google Scholar 

  19. Miyahara M, Tanuma J, Sugihara K, Semba I (2007) Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Cancer 110:1287–1294

    Article  PubMed  Google Scholar 

  20. Xuan M, Fang YR, Wato M, Hata S, Tanaka A (2005) Immunohistochemical co-localization of lymphatics and blood vessels in oral squamous cell carcinomas. J Oral Pathol Med 34:334–339

    Article  PubMed  Google Scholar 

  21. Zhao D, Pan J, Li XQ, Wang XY, Tang C, Xuan M et al (2008) Intratumoral lymphangiogenesis in oral squamous cell carcinoma and its clinicopathological significance. J Oral Pathol Med 37:616–625

    Article  CAS  PubMed  Google Scholar 

  22. Frech S, Hormann K, Riedal F, Gotte K (2009) Lymphatic vessel density in correlation to lymph node metastasis in head and neck squamous cell carcinoma. Anticancer Res 29:1675–1679

    PubMed  Google Scholar 

  23. Chung MK, Min JY, So YK, Ko YH, Jeong HS, Son YI et al (2010) Correlation between lymphatic vessel density and regional metastasis in squamous cell carcinoma of the tongue. Head Neck 32:445–451

    PubMed  Google Scholar 

  24. Baradaranfar BH, Zahir ST, Atighechi S, Dadgarnia MH, Bayati F, Mohajerani MR (2011) Lymphatic metastasis in head and neck squamous cell carcinoma. Pak J Med Sci 27:303–306

    Google Scholar 

  25. Franchi A, Gallo O, Massi D, Baroni G, Santucci M (2004) Tumor lymphangiogenesis in head and neck squamous cell carcinoma: a morphometric study with clinical correlations. Cancer 101:973–978

    Article  PubMed  Google Scholar 

  26. Audet N, Beasley NJ, Macmillion C, Jackson DG, Gullane PJ, Kamel-Reid S (2005) Lymphatic vessel density, nodal metastases, and prognosis in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 131:1065–1070

    Article  PubMed  Google Scholar 

  27. Beasley NJ, Prevo R, Banerji S, Leek RD, Moore J, Cox G et al (2002) Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res 62:1315–1320

    CAS  PubMed  Google Scholar 

  28. Kyzas PA, Geleff S, Batistatou A, Agnantis NJ, Stefanou D (2005) Evidence for lymphangiogenesis and its prognostic implications in head and neck squamous cell carcinoma. J Pathol 206:170–177

    Article  PubMed  Google Scholar 

  29. Longatto Filho A, Oliveira TG, Pinheiro C, De Carvalho MB, Curioni OA, Mercante AM et al (2007) How useful is the assessment of lymphatic vascular density in oral carcinoma prognosis? World J Surg Oncol 5:140

    Article  PubMed  PubMed Central  Google Scholar 

  30. Stinga AS, Stinga AC, Margaritescu C, Stepan AE, Barca A, Cruce M (2009) Lymphatic vessels in tumor invasion front of squamous cell carcinoma of the oral tongue. Ann RSCB 14:180–186

    Google Scholar 

  31. Yuan P, Temam S, El-Naggar A, Zhou X, Liu DD, Lee JJ et al (2006) Overexpression of podoplanin in oral cancer and its association with poor clinical outcome. Cancer 107:563–569

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, PT BDS PGIMS, Rohtak, Haryana, 124001, India

    Padam Parmar, Nisha Marwah, Ashima Batra & Rajeev Sen

  2. Department of Surgery, PT BDS PGIMS, Rohtak, Haryana, India

    Sanjeev Parshad

  3. Department of Radiodiagnosis, PT BDS PGIMS, Rohtak, Haryana, India

    Taruna Yadav

Authors
  1. Padam Parmar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nisha Marwah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanjeev Parshad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Taruna Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ashima Batra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rajeev Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Padam Parmar.

Ethics declarations

Conflict of interest

All authors state that there are no conflicts of interests.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Parmar, P., Marwah, N., Parshad, S. et al. Clinicopathological Significance of Tumor Lymphatic Vessel Density in Head and Neck Squamous Cell Carcinoma. Indian J Otolaryngol Head Neck Surg 70, 102–110 (2018). https://doi.org/10.1007/s12070-017-1216-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12070-017-1216-0

Keywords

Search

Navigation