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Expression of Matrix Metalloproteinases and Their Inhibitors Correlates With Invasion and Metastasis in Squamous Cell Carcinoma of the Head and Neck
Pornchai O-charoenrat, MD;
Peter H. Rhys-Evans, FRCS;
Suzanne A. Eccles, PhD
Arch Otolaryngol Head Neck Surg. 2001;127:813-820.
Background Matrix metalloproteinases (MMPs) have been implicated in the invasion
and metastasis of head and neck squamous cell carcinoma (HNSCC). However,
a detailed analysis of MMPs and tissue inhibitors of MMPs (TIMPs) in relation
to the biological behavior of HNSCC has yet to be performed in clinical material.
Objectives To study a comprehensive profile of MMPs and their 2 main inhibitors
in HNSCC tissue samples and to correlate the patterns of expression with clinicopathological
characteristics, invasion, and metastasis.
Design This study included 54 consecutive patients with primary HNSCC, 27 of
which showed lymph node metastasis. Expression of MMP-1, MMP-2, MMP-3, MMP-7,
MMP-9, MMP-10, MMP-11, MMP-13, MMP-14, TIMP-1, and TIMP-2 was simultaneously
analyzed in tissue homogenates using semiquantitative reverse transcription–polymerase
chain reaction assay. Where feasible, levels of protein and enzyme activity
were confirmed by Western blot, enzyme-linked immunosorbent assay, and substrate
zymography. Conventional clinicopathological features, including mode of tumor
invasion, were also examined.
Results Significantly higher MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-11,
MMP-13, and TIMP-1 levels were found in tumors vs specimens of matched normal
mucosa. No difference in the distribution of MMPs and TIMPs in relation to
age, sex, tumor site, or histological grade was observed. A significant correlation
was demonstrated between levels of MMP-1, MMP-9, and TIMP-1 and advanced T
stage and between MMP-9 expression and an infiltrative pattern of growth.
Enhanced expression of MMP-9 was strongly correlated (P<.001) and levels of MMP-2, MMP-7, and MMP-11 were weakly correlated
(P = .03-.05) with lymph node involvement.
Conclusions Overexpression of multiple MMPs and TIMPs is characteristic of HNSCC,
and analysis of specific MMPs, MMP-9 in particular, might be useful for evaluating
the malignant potential in individual HNSCC.
From the Division of Head and Neck Surgery, Department of Surgery,
Siriraj Hospital Medical School, Bangkok, Thailand (Dr O-charoenrat); the
Head and Neck Unit, Royal Marsden Hospital, London, England (Dr Rhys-Evans);
and the Section of Cancer Therapeutics, Institute of Cancer Research, Sutton,
England (Dr Eccles).
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