The pT1a and pT1b category subdivision in renal cell carcinoma: is it reflected by differences in tumour biology?

To assess systematically the possible differences in pathology between pT1a and pT1b renal cell carcinomas (RCCs), as the sixth edition of the Tumour-Nodes-Metastasis (TNM) system implemented a subdivision of category pT1 into pT1a (<4 cm) and pT1b (4-7 cm), based on clinical outcome analysis and the approach to therapy. Conventional histopathology and immunohistochemical expression of several biomarkers were analysed in 66 patients with pT1a and 29 with pT1b RCCs, using a tissue microarray technique. After 2 years of follow-up, none of the 66 patients with pT1a and three of the 29 with pT1b tumours developed progressive disease. The tumour was grade 3 in four (6%) pT1a and 11 (38%) pT1b RCCs. Immunohistochemically, pT1a RCCs were characterized by strong expression of p27 (79%), bcl-2 (67%), MUC1 (87%), insulin-like growth factor (IGF)-I (71%) and CD10 (88%), as well as moderate expression of IGF-I receptor (43%) and low expression of epidermal growth factor receptor (EGFR, 20%). During progression to category pT1b, expression of p27 significantly decreased (54%) and EGFR expression increased (38%). Moreover, membranous staining patterns of MUC1 and CD10 changed from apical to circumferential in clear cell RCCs. p53 (pT1a 23%, pT1b 28%), E-cadherin (10% and 17%), MIB-1 (1.2% and 1.5%) and Skp2 (2% and none) expression seemed to be of minor importance. This is the first study to show that the subdivision of category pT1 implemented in the latest issue of the TNM system is reflected by differences in conventional histopathology and expression of biomarkers.