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*HEAD & NECK CUTANEOUS SQUAMOUS CELL CARCINOMA – UNDERSTANDING THE TUMOUR MICROENVIRONMENT
Author(s) -
Ch’ng S.,
Low I.,
Brasch H.,
Sullivan M.,
Davis P.,
Tan S. T.
Publication year - 2009
Publication title -
anz journal of surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.426
H-Index - 70
eISSN - 1445-2197
pISSN - 1445-1433
DOI - 10.1111/j.1445-2197.2009.04927_11.x
Subject(s) - lymphangiogenesis , stromal cell , pathology , medicine , angiogenesis , tumor microenvironment , metastasis , cancer research , lymphatic system , immune system , immunology , cancer
Background: HNcSCC is common in Australasia. Recent advances have led to new paradigms in our understanding of the complex interactions between tumour, stromal and immune cells, and the extracellular matrix. The deranged interplay between tumour and its microenvironment eventually spirals towards irreversibility. The repertoire of gene expression in the tumour becomes increasingly abnormal, and results in metastasis. Purpose: To examine the tumour microenvironment including, tumour immunosurveillance, angiogenesis and lymphangiogenesis, and investigate the expression of EGFR, which is fundamental to skin physiology, in HNcSCC. Methods: Archived HNcSCC specimens were stratified into groups of primary lesions with and without metastasis. (Immuno) histochemical analysis was performed for the differential parameters of peritumoural mast cell, microvessel and lymphatic vessel densities, VEGF and EGFR expression. The effects of mast cells on cell cycle and apoptotic gene expression were studied using cell co‐culture and cDNA micro‐array. The mechanism of EGFR over‐expression in metastatic HNcSCC and its potential link with HER2 were assessed with fluorescence in‐situ hybridisation. Results: Although mast cells demonstrate a tumour inhibitory effect by deregulating the cell cycle and apoptosis in vitro, this observation is not corroborated by study of tissue specimens. Lymphatic vessel density (but not microvessel density or VEGF expression) predicts metastatic potential. 75% of primary HNcSCC that subsequently metastasise over‐express EGFR, with the majority harbouring HER2 polysomy. Conclusion: Improved understanding of the tumour microenvironment will hopefully lead to development of novel biologic therapy for HNcSCC.