Immunohistochemical localization of plakophilins (PKP1, PKP2, PKP3, and p0071) in primary oropharyngeal tumors: correlation with clinical parameters.

Plakophilins (PKPs) are members of the armadillo multigene family. Armadillo-related proteins function in both cell adhesion and signal transduction, and also play a central role in tumorigenesis. Here we report the immunohistochemical localization of PKPs in 37 cases of human primary squamous cell carcinoma of the oropharynx lacking overt distant metastases that were followed clinically for 3 years. Immunoreactivity for the PKPs PKP1, PKP2, PKP3, and p0071 (also known as PKP4) was assessed on frozen unfixed sections using a semiquantitative scoring system. Results were correlated with tumor grade, clinicopathologic parameters, and patient survival. Only p0071 was associated with tumor growth, demonstrating an inverse correlation with tumor size. PKP1 and PKP3 immunoreactivity was inversely correlated with tumor histological grade and was observed only in tumors that did not metastasize. In contrast, strong PKP2 immunoreactivity was observed in 85.7% of metastatic tumors. Interestingly, patients with tumors in which PKP1 and PKP3 immunoreactivity was reduced or absent exhibited local recurrences or metastases, or both, as well as poor survival. Correlation of the subcellular localization of PKPs with routine histological and clinical parameters suggests that these proteins may serve as useful markers for predicting the clinical outcome of the disease. Although the 4 PKPs displayed different levels and patterns of subcellular distribution in tumors, there was a positive correlation between immunoreactivity for PKP2 and PKP3, as well as for PKP2 and p0071, suggesting possible functional similarities associated with differentiation, tumor growth, and disease prognosis. Nevertheless, the mechanisms involved in altering the subcellular localization in tumors compared with normal epithelium are unknown, and further investigation is needed to determine whether PKPs are causative factors for oral carcinogenesis or are merely characteristic of the phenotype.