Elsevier

Human Pathology

Volume 33, Issue 7, July 2002, Pages 708-714
Human Pathology

Original Contributions
Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma*

https://doi.org/10.1053/hupa.2002.125376Get rights and content

Abstract

Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications. The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E2 (PgE2) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan–Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan–Meier analysis, patients with COX-2 tumor overexpression and with higher PgE2 tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE2 tumor levels. This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer. HUM PATHOL 33:708-714. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Patients and methods

We studied 52 consecutive patients affected by HNSCC who underwent surgical treatment of the primary tumor and of the neck at the Department of Otolaryngology Head and Neck Surgery, University of Florence, from April 1995 through April 1998. There were 41 men (78.8%) and 11 women (21.2%) with a mean age of 62.3 years (range, 50 to 74 years). Twenty-two patients suffered from laryngeal, 18 from oral cavity, and 12 from oropharyngeal SCC. Tumors were graded as well differentiated, moderately

COX-2 expression and PgE2 production in head and neck cancer

Overall, 37 of 52 (71.1%) squamous cell carcinomas studied showed cytoplasmic immunoreactivity for COX-2 in neoplastic cells (Fig 1).

. Focal (+; A) and diffuse (+++; B) COX-2 expression in squamous cell carcinomas of the oral cavity.

Twenty (54.1%) of these showed a moderate or diffuse immunostaining. COX-2 immunoreactivity was significantly higher in tumors with histologically confirmed cervical lymph node metastasis than in with tumors without neck involvement (Table 1; P = 0.0001).Moreover,

Discussion

In this study we confirm in a larger series of patients our previous results on frequent COX-2 overexpression in HNSCC when compared with adjacent normal tissue, which is accompanied by an increase in PgE2 production, particularly at the tumor edge.26 The levels of COX-2 expression detected in this study are comparable to those of colon cancer30 and of adenocarcinoma of the lung.8 In addition, the high rate of COX-2 expression in HNSCC is in agreement with the results of Chan et al.9 on HNSCCs,

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    *

    Address correspondence and reprint requests to Alessandro Franchi, MD, Department of Human Pathology and Oncology, University of Florence, V.le Morgagni 85, 50134 Florence, Italy.

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