Clinicopathologic characteristics of KIT and protein kinase C-δ expression in adenoid cystic carcinoma: Comparison with chromophobe renal cell carcinoma and gastrointestinal stromal tumor

Abstract

Aims

KIT overexpression is frequently observed in adenoid cystic carcinomas (AdCCs), chromophobe renal cell carcinomas (ChRCCs), and gastrointestinal stromal tumor (GISTs). Persistent KIT activation has been reported to be mediated by protein kinase C (PKC)-δ in a subset of colon cancers with wild-type KIT overexpression and by PKC-θ in GISTs with mutant KIT overexpression. To elucidate the clinical implications of PKC-δ and PKC-θ expression in KIT-expressing tumors, we investigated the expression of KIT, PKC-δ, and PKC-θ in AdCCs and ChRCCs in comparison to GISTs.

Methods and Results

The expression of KIT, PKC-δ and PKC-θ was analyzed in whole sections from 41 AdCCs, 40 ChRCCs, and 56 GISTs by immunohistochemistry. Membranous expression of KIT was found in 34 AdCCs and all of ChRCCs, while cytoplasmic expression of KIT was found in 46 GISTs. In AdCCs, PKC-δ expression was associated with histologic grade (p=0.049), lymphovascular invasion (p=0.004), perinueral invasion (p=0.002), and KIT positivity (p=0.002). PKC-δ positivity was associated with shorter relapse-free survival (RFS; p=0.017) and a tendency toward shorter overall survival (OS; p=0.090) in AdCCs. No clinicopathologic associations were observed between PKC-δ and KIT expression in ChRCCs. In GISTs, PKC-θ expression was associated with higher mitotic count (p=0.011) and high grade according to the modified NIH criteria (p<0.001). PKC-θ positivity was associated with shorter RFS (p=0.016) and a tendency toward shorter OS (p=0.051) in GISTs.

Conclusions

PKC-δ expression is associated with KIT expression and patient prognosis in AdCCs, suggesting that PKC-δ may be a potential therapeutic target for AdCCs.

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