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Prognostic value of lymphangiogenesis in supraglottic laryngeal carcinoma

  • J Y Lin (a1), X Y Li (a2), P Dong (a1) and T Nakashima (a3)

Abstract

Background:

Metastasis to regional lymph nodes via lymphatic microvessels plays a key role in cancer progression, and is an important prognostic factor in many cancers. Recent evidence suggests that tumour lymphangiogenesis promotes lymphatic metastasis.

Aims:

To investigate whether tumour lymphatic microvessel density correlates with clinicopathological factors and serves as a prognostic indicator of supraglottic laryngeal carcinoma progression.

Methods:

The lymphatics of 84 supraglottic laryngeal carcinoma cases were investigated by immunohistochemical staining for podoplanin (also termed D2-40). The relationships between (intra- and peritumoural) lymphatic microvessel density, clinicopathological parameters and clinical prognosis were analysed.

Results:

There was a significant relationship between high intratumoural lymphatic microvessel density and aggressive tumour node stage (p < 0.0001), distant metastasis (p = 0.037) and poor prognosis (p = 0.011), and between high peritumoural lymphatic microvessel density and node stage (p = 0.004) and poor prognosis (p = 0.029). Patients with high lymphatic microvessel density also had significantly worse disease-free survival (p = 0.003) and overall survival (p = 0.005). Intratumoural lymphatic microvessel density was found to be an independent prognostic factor for overall survival (p = 0.008) and disease-free survival (p = 0.005) (multivariate analysis).

Conclusion:

Lymphatic microvessel density (detected by podoplanin immunohistochemistry), especially intratumoural density, may be an independent predictor of lymphatic tumour spread and survival in supraglottic laryngeal carcinoma patients, and may be useful to guide decisions regarding additional surgery.

Copyright

Corresponding author

Address for correspondence: Dr Xiao Yan Li, Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiaotong University Affiliated Children's Hospital, 1400 West Beijing Road, Shanghai 200040, People's Republic of China E-mail: tiancheng15@live.cn

References

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1Jemal, A, Murray, T, Ward, E, Samuels, A, Tiwari, R, Ghafoor, A et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55:1030
2Forastiere, A, Koch, W, Trotti, A, Sidransky, D. Head and neck cancer. N Engl J Med 2001;345:1890–900
3Boring, CC, Squires, TS, Tong, T. Cancer statistics, 1992. CA Cancer J Clin 1992;42:1938
4Van Netten, JP, Cann, SA, Maxwell, CA, Finegan, RP. Lymphagenesis and cancer metastasis. Br J Cancer 1998;78:277–8
5Van Netten, JP, Cann, SA, van der Westhuizen, NG. Angiogenesis and tumor growth. N Engl J Med 1996;334:920–1
6Breiteneder-Geleff, S, Soleiman, A, Kowalski, H, Horvat, R, Amann, G, Kriehuber, E et al. Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 1999;154:385–94
7Stacker, SA, Caesar, C, Baldwin, ME, Thornton, GE, Williams, RA, Prevo, R et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med 2001;7:186–91
8Straume, O, Jackson, DG, Akslen, LA. Independent prognostic impact of lymphatic vessel density and presence of low-grade lymphangiogenesis in cutaneous melanoma. Clin Cancer Res 2003;9:250–6
9Dadras, SS, Paul, T, Bertoncini, J, Brown, LF, Muzikansky, A, Jackson, DG et al. Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival. Am J Pathol 2003;162:1951–60
10Schacht, V, Dadras, SS, Johnson, LA, Jackson, DG, Hong, YK, Detmar, M. Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. Am J Pathol 2005;166:913–21
11Kato, Y, Kaneko, M, Sata, M, Fujita, N, Tsuruo, T, Osawa, M. Enhanced expression of aggrus (T1alpha/podoplanin), a platelet-aggregation-inducing factor in lung squamous cell carcinoma. Tumour Biol 2005;26:195200
12Dumoff, KL, Chu, CS, Harris, EE, Holtz, D, Xu, X, Zhang, PJ. Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation. Mod Pathol 2006;19:708–16
13Giorgadza, TA, Baloch, ZW, Pasha, T, Zhang, PJ, LiVolsi, VA. Lymphatic and blood vessel density in the follicular patterned lesions of thyroid. Mod Pathol 2005;18:1424–31
14Kyzas, PA, Geleff, S, Batistatou, A, Agnantis, NJ, Stefanou, D. Evidence for lymphangiogenesis and its prognostic implications in head and neck squamous cell carcinoma. J Pathol 2005;206:170–7
15Kaplan, EL, Meier, P. Non parametric estimation from incomplete observations. J Am Statist Assoc 1958;53:457–81
16Marcus, B, Arenberg, D, Lee, J, Kleer, C, Chepeha, DB, Schmalbach, CE et al. Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma. Cancer 2004;101:2779–87
17Breiteneder-Geleff, S, Soleiman, A, Horvat, R, Amann, G, Kowalski, H, Kerjaschki, D. Podoplanin – a specific marker for lymphatic endothelium expressed in angiosarcoma [in German]. Verh Dtsch Ges Pathol 1999;83:270–5
18Kriehuber, E, Breiteneder-Geleff, S, Groeger, M, Soleiman, A, Schoppmann, SF, Stingl, G et al. Isolation and characterization of dermal lymphatic and blood endothelial cells reveal stable and functionally specialized cell lineages. J Exp Med 2001;194:797808
19Padera, TP, Kadambi, A, di Tomaso, E, Carreira, CM, Brown, EB, Boucher, Y et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 2002;296:1883–6
20Skobe, M, Hawighorst, T, Jackson, DG, Prevo, R, Janes, L, Velasco, P et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nature Med 2001;7:192–8
21Cao, Y. Opinion: emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis. Nat Rev Cancer 2005;5:735–43
22Altman, DG, Lausen, B, Sauerbrei, W, Schumacher, M. Dangers of using ‘optimal’ cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst 1994;86:829–35
23Concato, J, Feinstein, AR, Holford, TR. The risk of determining risk with multivariable models. Ann Intern Med 1993;118:201–10
24Birner, P, Schindl, M, Obermair, A, Breitenecker, G, Kowalski, H, Oberhuber, G. Lymphatic microvessel density as a novel prognostic factor in early stage invasive cervical cancer. Int J Cancer 2001;95:2933
25Munoz-Guerra, MF, Marazuela, EG, Martin-Villar, E, Quintanilla, M, Gamallo, C. Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity. Cancer 2004;100:553–60
26Reis-Filho, JS, Schmitt, FC. Lymphangiogenesis in tumors: what do we know? Microsc Res Techn 2003;60:171–80
27Jain, RK, Fenton, BT. Intratumoral lymphatic vessels: a case of mistaken identity or malfunction? J Natl Cancer Inst 2002;94:417–21
28Stacker, SA, Achen, MG, Jussila, L, Baldwin, ME, Alitalo, K. Lymphangiogenesis and cancer metastasis. Nat Rev Cancer 2002;2:573–83
29Maula, SM, Luukkaa, M, Grénman, R, Jackson, D, Jalkanen, S, Ristamäki, R. Intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region. Cancer Res 2003;63:1920
30Frech, S, Hörmann, K, Riedel, F, Götte, K. Lymphatic vessel density in correlation to lymph node metastasis in head and neck squamous cell carcinoma. Anticancer Res 2009;29:1675–9

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