p63 Expression in Merkel Cell Carcinoma: Comparative immunohistochemistry invokes TAp63 as the dominant isoform involved

Summary The literature suggests that p63 expression in Merkel cell carcinoma (MCC) is associated with a poor prognosis. p63 immunohistochemistry marks the two main isoforms of this transcriptional protein, TAp63 (tumor-suppressor-like properties) and ∆Np63 (oncogenic properties). Little information about the isoform of relevance in MCC exists. p40 immunohistochemistry specifically marks ∆Np63 and using comparative, semiquantitative expression of p63 and p40 we sought to clarify the issue. Our cohort of 53 cases [28 males and 25 females, median age 79 years, (interquartile range {IQR} 71-88)] was stratified by morphology and viral status. Immunohistochemistry (p63, p40 and CK5/6) was performed, H-scores for nuclear expression of p63 and p40 were derived (2 observers; positivity ≥ 10) and inter-observer agreement was evaluated. Clinical, pathological and outcome data were documented. The results were analyzed statistically. Mortality amounted to 57% (median follow-up 686 days, IQR 292-1599). Positivity for MCPyV was observed in 29 (55%) of cases. Expression of p63 and p40 was present in 36 (69%) and 4 (8%) of cases, respectively. Increased age (p=0.0241), negative MCPyV status (p=0.0185) and p63 positivity (p=0.0012) were significantly associated with mortality. The latter 2 variables were highly correlated (p=0.004). The interclass correlation between the two sets of H-scores was 0.95. Our findings support an association between p63 expression and reduced overall survival in MCC and show consistency in scoring this prognostic parameter. TAp63 is the dominant isoform of the protein involved. The paradoxical tumor suppressor-like activity of this isoform in p63 positive MCCs with reduced overall survival requires further study.