| Epidermal Growth Factor Receptor |
Receptor for growth factors (TGF and EGF) with tyrosine kinase activity. Upstream activator of MAPkinase pathway and of other pathways involved in cell growth, cell migration, block of apoptosis (Fig. 1). |
Frequently and early overexpressed in LSCC, mainly by post– translational mechanisms. At present, the most reliable biological marker for molecular characterization. Marker of aggressiveness4,7 and of invasiveness 1. |
| Overexpression and amplification of cyclin D1 gene (CCND1) |
Cyclin D1 gene transcriptional activity normally strictly depends on mitogen stimulation, and leads to cell commitment to mitosis through START checkpoint. |
Early CCND1 overexpression is often detectable without evidence of gene amplification, it can be used for molecular epidemiology but it seems to retain a lower prognostic value, if compared with CCND1 amplification, marker of aggressiveness in LSCC 5. Its role as marker of invasiveness is still unproven. |
| Cathepsin D |
Lytic enzyme active in extracellular matrix rearrangement |
Overexpression is often detectable in tumour cells, where it seems to contribute to invasiveness 8. |
| S100–A2 Ca2+ binding protein |
Increasing levels of expression during differentiation of squamous epithelial cells; absent in basal layers. |
Underexpression in cancer cells, inversely proportional to tumour differentiation. Starting from data concerning NSCLC, a role as a real oncosuppressor has been hypothesized 44. It may act as a marker both of aggressiveness and of invasiveness. |
| Methyl–p– hydroxyphenyllactate esterase (MEPHLase) activity |
Enzyme involved in the metabolism of methyl–p–hydroxyphenyllactate, ligand of type II EBS, with a role in growth and differentiation of several tissues (breast, uterus), normally expressed in larynx. |
In LSCC, a low activity is associated with poor differentiation, and shorter overall survival and metastasis–free survival 85. |
| Type 2 cyclo– oxigenase 2 (Cox–2) |
Enzyme involved in arachidonic acid metabolism and autacoid synthesis, induced by various stimuli in several cell types. Inhibited by FANS. |
Cox–2 activity seems to promote tumour neoangiogenesis. Nevertheless, evidence exists showing that low Cox–2 expression indicates poor differentiation and higher |
