Abstract
Thymidine phosphorylase (Th.P) is an angiogenic factor shown to induce endothelial cell migration and proliferation. On the other hand, loss of wild type p53 function leads to down-regulation of thrombospondin-1, an inhibitor of angiogenesis. In this immunohistochemical study we investigated the intratumoural angiogenesis and thymidine phosphorylase (Th.P) expression in paraffin-embedded bioptical material from 104 locally advanced squamous cell head and neck cancers. The nuclear accumulation of mutant p53 protein and the cytoplasmic expression of bcl-2 protein was also assessed. High vascular grade was observed in 56% and high Th.P tumour cell reactivity in 48% of cases. High microvessel score was associated with an increased percentage of cancer cells expressing thymidine phosphorylase (P = 0.001). Increased p53 nuclear accumulation also corre-lated with high vascular grade (P = 0.001). High histological grade and absence of bcl-2 overexpression were associated with lymph node involvement (P = 0.002 and P = 0.02 respectively). No correlation of clinically detected lymphadenopathy with angiogenesis and p53 was observed. We conclude that intense neo-angiogene-sis in locally advanced squamous cell head neck cancer is a frequent event, which is associated with nuclear p53 accumulation and thymidine phosphorylase overexpression. ©Lippincott Williams & Wilkins
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References
Horak ER, Russel L, Klenk N, et al.,1992, Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet, 340, 1120-4.
Fontanini G, Bigini D, Vignati S, et al.,1995, Microvessel count predicts metastatic disease and survival in non-small cell lung cancer. J Pathol, 177, 57-63.
Giatromanolaki A, Koukourakis M, O'Byrne K, et al.,1996, Prognostic value of angiogenesis in operable non-small cell lung cancer. J Pathol, 179, 80-8.
Ferrara N, Houck K, Jakeman L and Leung DW, 1992, Molecular and biological properties of vascular endothelial growth factor family of proteins. Endocrine Rev, 13, 18-32.
Klagsbrun M, 1989, The fibroblast growth factor family: structural and biological properties. Prog Growth Res, 1, 207-35.
Moghaddam A, Zhang HT, Fan Th.PD, et al.,1995, Thymidine phosphorylase is angiogenic and promotes tumour growth. Proc Natl Acad Sci USA, 92, 998-1002.
Dameron KN, Volpert OV, Tainsky MA and Bouck N, 1994, Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science, 265, 1582-4.
Fontanini G, Vignati S, Bigini D, et al.,1995, Bcl-2 protein: a prognostic factor inversely correlated to p53. Br J Cancer, 71, 1003-7.
Koukourakis M, Giatromanolaki A, O'Byrne K, et al.,1998, Potential role of bcl-2 as a suppressor of tumour angiogenesis in non small cell lung cancer. Int J Cancer, 74, 565-70.
Merino OR, Lindberg RD and Fletcher GH, 1977, An analysis of distant metastases from squamous cell carcinoma of the upper respiratory and digestive tract. Cancer, 40, 145-51.
Choksi AJ, Dimery IW and Hong WK, 1998, Adjuvant chemotherapy of head and neck cancer: the past, the present and the future. Semin Oncol, 15, 45-59.
van-Dongen GA, Brakenhoff RM, ten Brink CT, et al.,1996, Squamous cell carcinoma-associated antigens used in novel strategies for the detection and treatment of minimal residual head and neck cancer. Anticancer-Res, 16, 2409-13.
Gath HJ, Heissler E, Hell B, et al.,1998, Minimal residual disease in bone marrow of patients with squamous cell carcinomas in the head and neck region. Br J Cancer, 77(Suppl 1), 2.
Koukourakis M, Whitehouse R, Giatromanolaki et al.,1996, Predicting distant failure in nasopharyngeal cancer. Laryngoscope, 106, 765-71.
The department of Veterans Affairs Laryngeal Cancer Study Group, Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. 1991, N Engl J Med, 324, 1656-7.
Million RR, Cassissi NJ and Clark JR, 1995, Cancer of the head and neck. In: DeVita VT, Hellman S, Rosenberg SA, eds, Principles and Practice of Oncology. Philadelphia: JB Lippincott, 3rd edn, pp 488-590.
Koukourakis M, Skarlatos J, Kosma L, et al.The department of Veterans Affairs Laryngeal Cancer Study Group, 1996, Radiotherapy alone for non-small cell lung carcinoma. Acta Oncol, 34, 525-30.
Macchiarini P, Fontanini G, Hardin MJ, The department of Veterans Affairs Laryngeal Cancer Study Group, 1992, Relation of neovascularisation to metastasis of non small cell lung cancer. Lancet, 340, 145-6.
American Joint Committee for Cancer Staging and End Results Reporting. Manual for Staging of Cancer,1988, 3rd edition. Chicago: The American Joint Committee.
Dunstan S, Powe DG, Wilkinson M, et al.,1997, The tumour stroma of oral squamous cell carcinomas show increased vascularity compared with adjacent host tissue. Br J Cancer, 75, 559-65.
Giatromanolaki A, Koukourakis M, Theodossiou D, et al.,1997, Comparative evaluation of angiogenesis assessment with anti-Factor VIII and anti-CD31 immunostaining in non small cell lung cancer. Clin Cancer Res, 3, 2493-500.
Giatromanolaki A, Koukourakis M, Comley M, et al.,1997, Platelet-derived endothelial cell growth factor (thymidine phosphorylase) expression in lung cancer. J Pathol, 181, 196-9.
Weidner N, Semple JP, Welch WR and Folkman J, 1991, Tumour angiogenesis and metastasis correlation in invasive breast carcinoma. N Engl J Med, 324, 1-8.
Heimann R, Ferguson D, Powers C, et al.,1996, Angiogenesis as a predictor of long term survival for patients with node-negative breast cancer. J Natl Cancer Inst, 88, 1764-9.
Costello P, McCann A, Carney DN and Dervan MD, 1995, Prognostic significance of microvessel density in lymph node negative breast carcinoma. Hum Pathol,26, 1181-4.
Goulding H, Robertson JF, Elston CW, et al.,1995, Assessment of angiogenesis in breast carcinoma: an important factor in prognosis? Hum Pathol, 26, 1196-200.
Harpole DH, Richards WG, Herndon JE and Sugarbaker DJ, 1996, Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer. Ann Thor Surg, 61, 1470-6.
Pezzella F, Di Bacco A, Andreola S, et al.,1996, Angiogenesis in primary lung cancer and lung secondaries. Eur J Cancer, 32, 2494-500.
Giatromanolaki A, Koukourakis M, O'Byrne K, et al.,1996, Non small cell lung cancer: C-erbB-2 correlates with low angiogenesis and poor prognosis. Anticancer Res, 16, 3819-25.
Gasparini G, Weidner N, Maluta S, et al.,1993, Intratumoural microvessel density and p53 protein: correlation with metastasis in head and neck squamous cell carcinoma. Int J Cancer, 55, 739-44.
Klijanienko J, el Naggar AK, de Braud F, et al.,1995, Tumour vasculariazation, mitotic index, histopathologic grade, and DNA ploidy in the assessment of 114 head and neck squamous cell carcinomas. Cancer, 75, 1649-56.
Penfold CN, Partridge M, Rojas R and Langdon JD, 1996, The role of angiogenesis in the spread of oral squamous cell carcinoma. Br J Oral Maxillofac Surg,34, 37-41.
Mikami Y, Tsukuda M, Itao et al.,1996, Peritumoural angiogenesis in carcinomas of the head and neck. Auris Nasus Larynx, 23, 57-62.
Shpitzer T, Chaimoff M, Gal R, et al.,1996, Tumour angiogenesis as a prognostic factor in early oral tongue cancer. Arch Otolaryngol Head Neck Surg, 122, 865-8.
Carrau RL, Barnes EL, Snyderman CH, et al.,1995, Tumour angiogenesis as a predictor of tumour agressiveness and metastatic potential in squamous cell carcinoma of the head and neck. Invasion Metastasis,15, 197-202.
Zatterstrom UK, Brun E, Willen R, et al.,1995, Tumour angiogenesis and prognosis in squamous cell carcinoma of the head and neck. Head-Neck, 17, 312-18.
Leedy DA, Trune DR, Kronz JD, et al.,1994, Tumour angiogenesis, the p53 antigen and cervical metastasis in squamous carcinoma of the tongue. Otolaryngol Head Neck Surg, 111, 417-22.
Gleich LL, Biddinger PW, Pavelic ZP and Gluckman JL, 1996, Tumour angiogenesis in T1 oral cavity squamous cell carcinoma: role in predicting tumour aggressiveness. Head-Neck, 18, 343-6.
Albo D, Granick MS, Jhala N, et al.,1994, The relationship of angiogenesis to biological activity in human squamous cell carcinoma of the head and neck. Ann Plast Surg, 32, 588-94.
Alvi A and Johnson JT, 1996, Extracapsular spread in the clinically negative neck (N0): implications and outcome. Otolaryngol-Head-Neck-Surg, 114, 65-70.
Takahashi Y, Bucana CD, Liu W, et al.,1996, Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: Role of infiltrating cells. J Natl Cancer Inst, 88, 1146-51.
Kaklamanis L, Kakolyris S, Turley et al.,1998, Neoplastic stroma and epithelium show up-regulation of platelet-derived endothelial cell growth factor/thymidine phosphorylase, in colorectal carcinomas but not in adenomas. Angiogenesis, 2, 49-55.
Koukourakis MI, Giatromanolaki A, et al.,1997, Platelet-derived endothelial cell growth factor expression correlates with tumour angiogenesis and prognosis in non-small cell lung cancer. Br J Cancer, 4, 477-81.
Toi M, Hoshina S, Taniguchi T, et al.,1995, Vascular endothelial growth factor and platelet derived endothelial cell growth factor are frequently coexpressed in highly vascularized human breast cancer. Clin Cancer Res, 1, 961-4.
Giatromanolaki A, Koukourakis M, Kakolyris S et al.,1998, Vascular endothelial growth factor, wild-type p53 and angiogenesis in early operable non-small cell lung cancer, (in press)
Wilson GD, Grover R, Reachman PI, et al.,1996, Bcl-2 expression correlates with favourable outcome in head and neck cancer treated by accelerated radiotherapy. Anticancer Res, 16, 2403-8.
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Giatromanolaki, A., Fountzilas, G., Koukourakis, M.I. et al. Neo-angiogenesis in locally advanced squamous cell head and neck cancer correlates with thymidine phosphorylase expression and p53 nuclear oncoprotein accumulation. Clin Exp Metastasis 16, 665–672 (1998). https://doi.org/10.1023/A:1006554512338
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DOI: https://doi.org/10.1023/A:1006554512338