Proliferation of myofibroblasts in the stroma of renal oncocytoma

Abstract

Myofibroblasts are a vital component of stroma of many malignant neoplasms, but it is not yet established whether stromal myofibroblasts also exist in benign tumours such as oncocytoma of the kidney. Histomorphological and immunohistochemical analysis of 16 renal oncocytomas diagnosed at Chang Gung Memorial Hospital, Taiwan, has been performed. Renal oncocytomas were composed of oncocytes, large cells with granular eosinophilic cytoplasm, arranged mostly in sheets, in tubulocystic or combined pattern. Few oncocytes appeared to be undergoing proliferation or apoptosis. MIB-1 and active caspase 3 indices were low, but higher in tumour than in surrounding non-tumour parenchyma (MIB-1: 0.93 +/- 0.09 versus 0.46 +/- 0.07, P < 0.001 and active caspase 3: 0.76 +/- 0.08 versus 0.41 +/- 0.09, P < 0.001). Wnt/beta-catenin signalling was not implicated in this neoplasm, as there was no loss of E-cadherin membranous localization or expression of intranuclear beta-catenin in the cells. Clumps of oncocytes were stained with periodic acid Schiff and had collagen I-, collagen III- and fibronectin-positive, but desmin- and human caldesmon-negative stromas. Importantly, alpha-smooth muscle actin (SMA)-immunostaining established the myofibroblastic nature of many of the stromal cells. Some of the myofibroblasts were also positive for MIB-1, indicating a proliferative role for them in the stroma. Renal oncocytomas were composed of two independent compartments: benign oncocytes and pronounced fibrotic stroma, which consisted of proliferating myofibroblasts (SMA- and MIB-1-positive) which were associated with excessive deposition of extracellular matrix (periodic acid Schiff-component, collagen I-, collagen III- and fibronectin-positive, and desmin- and human caldesmon-negative).