Loss of desmoglein 1 expression associated with worse prognosis in head and neck squamous cell carcinoma patients

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.