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Heparanase Expression at the Invasion Front of Human Head and Neck Cancers and Correlation with Poor Prognosis

Authors' Affiliations: ¹ Tumor Immunology Program, German Cancer Research Center; ² Department of Pathology, University of Heidelberg; and Departments of ³ Head and Neck Surgery and ⁴ Neurosurgery University Hospital of Heidelberg, Heidelberg, Germany

Requests for reprints: Philipp Beckhove, Tumor Immunology Program, German Cancer Research Center, INF 280, 69120 Heidelberg, Germany. Phone: 49-6221-423745; Fax: 49-6221-423702; E-mail: P.Beckhove{at}dkfz.de.

Purpose: Head and neck squamous cell carcinomas (HNSCC) are characterized by a poor prognosis due to aggressive, recurrent tumor growth. Expression of the extracellular matrix–degrading enzyme heparanase was associated with poorer prognosis in several cancers. We analyzed the presence of heparanase in HNSCC tissues and tumor cells and its potential prognostic significance.

Experimental Design: We analyzed the expression of the active form of heparanase in HNSCC tissues in corresponding tumor cell cultures and after xenotransplantation of tumor cell cultures into NOD/Scid mice by immunohistochemistry, Western blot analysis, and reverse transcription-PCR in altogether 25 patients and did a comparison with clinicopathologic data of the patients.

Results: Heparanase expression in situ was detected in all tumor biopsies in the tumor stroma and in tumor cells from 13 of 19 primary tumors and 9 of 12 lymph node metastases. Heparanase was localized in disseminated tumor cells, in tumor cell clusters invading adjacent stromal tissues, and in tumor cells at the tumor invasion front. Lymph node metastases expressed higher levels of heparanase compared with corresponding primary tumors. In contrast to a heterogeneous expression pattern in tumor tissues, all corresponding HNSCC tumor cell cultures showed a rather homogeneous heparanase expression on the mRNA and protein levels. Comparison of heparanase expression in situ and in corresponding tumor cell cultures in vitro or after xenotransplantation into NOD/Scid mice revealed that heparanase expression was regulated in vivo. Lack of heparanase in tumor cells from primary tumors or lymph node metastases was correlated with prolonged disease-free survival and overall survival.

Conclusion: Heparanase expression seems to be involved in the invasiveness and aggressiveness of HNSCC.

Key Words: tumor invasion • NOD/Scid mice • primary tumor culture

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