Clinicopathological characteristics of KIT and protein kinase C-δ expression in adenoid cystic carcinoma: comparison with chromophobe renal cell carcinoma and gastrointestinal stromal tumour

Aims: KIT overexpression is frequently observed in adenoid cystic carcinomas (AdCCs), chromophobe renal cell carcinomas (ChRCCs), and gastrointestinal stromal tumours (GISTs). Persistent KIT activation has been reported to be mediated by protein kinase C (PKC)-delta in a subset of colon cancers with wild-type KIT overexpression, and by PKC-theta in GISTs with mutant KIT overexpression. To elucidate the clinical implications of PKC-delta and PKC-theta expression in KIT-expressing tumours, we investigated the expression of KIT, PKC-delta and PKC-theta in AdCCs and ChRCCs in comparison with GISTs. Methods and results: KIT expression, PKC-delta expression and PKC-theta expression were analysed in whole sections from 41 AdCCs, 40 ChRCCs and 56 GISTs by immunohistochemistry. Membranous expression of KIT was found in 34 AdCCs and all ChRCCs, whereas cytoplasmic expression of KIT was found in 46 GISTs. In AdCCs, PKC-delta expression was associated with histological grade (P = 0.049), lymphovascular invasion (P = 0.004), perineural invasion (P = 0.002), and KIT positivity (P = 0.002). PKC-delta positivity was associated with shorter relapse-free survival (RFS) (P = 0.017) and a tendency for there to be shorter overall survival (OS) (P = 0.090) in patients with AdCCs. No clinicopathological associations were observed between PKC-delta and KIT expression in ChRCCs. In GISTs, PKC-theta expression was associated with higher mitotic count (P = 0.011) and high grade according to the modified National Institutes of Health criteria (P < 0.001). PKC-theta positivity was associated with shorter RFS (P = 0.016) and a tendency for there to be shorter OS (P = 0.051) in patients with GISTs. Conclusions: PKC-delta expression is associated with KIT expression and the prognosis of patients with AdCCs, suggesting that PKC-delta may be a potential therapeutic target for AdCCs.