Aims:Mucosal squamous cell carcinomas are the most common head and neck malignancies. We hypothesised that over-expression of intracellular signalling proteins and decreased expression of desmoglein molecules would be associated with aggressive tumour behaviour in patients with head and neck squamous cell carcinoma.

Methods: Seventy-eight cases of head and neck squamous cell carcinoma were immunohistochemically stained for desmoglein 1, desmoglein 2, desmoglein 3, p53, bcl-2, vimentin, cyclin D1, p16, p21, p27, E-cadherin, and E2F-1 in paraffin-embedded tissue blocks in a microarray.

Results: The disease-specific survival was 56% at 5 years and 49% at 10 years. Expression of the desmoglein isotypes correlated positively with each other except for desmoglein 2 and desmoglein 3, which did not show a significant correlation. Desmoglein 1 and E-cadherin expression also correlated. On univariate analysis, only expression of desmoglein 1 correlated with patient outcome; lack of expression of desmoglein 1 was associated with a significantly worse disease-specific survival (p = 0.035). Hierarchical clustering analysis identified a subgroup of three patients with an immunophenotype distinct from the other tumours, characterised by co-expression of p16, p27, E2F-1 and bcl-2. Further statistical analysis of the prognostic significance of this small subgroup was not possible, but these three patients are alive and well.

Conclusions: Decreased expression of desmoglein 1 is associated with a worse prognosis in head and neck squamous cell carcinoma patients. Examination of an extended panel of immunomarkers revealed a rare subtype of squamous cell carcinoma characterised by the expression of multiple proliferation-associated markers and the anti-apoptotic protein, bcl-2; determination of the prognostic significance of this subgroup will require study of a larger case series.