Diagnostic Implications of Transcription Factor Pax 2 Protein and Transmembrane Enzyme Complex Carbonic Anhydrase IX Immunoreactivity in Adult Renal Epithelial Neoplasms

Abstract

Pax 2, expressed by metanephric mesenchyme is vital for renal tubule formation and development. Carbonic anhydrase IX (CA IX) is implicated in cell proliferation, adhesion, and invasion. Data regarding expression in renal epithelial tumors other than clear cell renal cell carcinoma (RCC) are limited, conflicting, from tissue microarrays, and do not encompass the entire spectrum or novel uncommon variants. Conventional sections from 200 renal tumors comprising clear cell RCC (n=30), oncocytoma (n=17), papillary RCC (n=30), chromophobe RCC (n=50), urothelial carcinomas (n=30), collecting duct carcinomas (n=5), renal tumors with Xp11.2 translocation (n=15), tubulocystic carcinoma (n=19), and mucinous tubular spindle cell carcinoma (n=4) were immunostained for Pax 2 and CA IX. Clear cell RCC (28/30, 93%), oncocytoma (17/17, 100%), papillary RCC (16/30, 53%), and mucinous tubular spindle cell carcinoma (3/4, 75%) demonstrated nuclear immunoreactivity with Pax 2, whereas the other subtypes were nonreactive. Clear cell RCC (30/30, 100%), urothelial carcinoma (27/30, 90%), papillary RCC (17/30, 57%), and renal tumors with Xp11.2 translocation (6/15, 40%) exhibited membranous immunoreactivity with CA IX, whereas the other subtypes were nonreactive. This suggests potential diagnostic utility of Pax 2 in distinction of (i) oncocytoma (positive) from chromophobe RCC (negative), (ii) clear cell RCC and papillary RCC (positive) from renal tumors with Xp11.2 translocation (negative), and (iii) high-grade clear cell RCC (positive) from urothelial carcinoma (negative). CA IX expression has potential diagnostic implications including (i) clear cell RCC (positive) versus chromophobe RCC (negative) and (ii) urothelial carcinoma (positive) versus collecting duct carcinoma (negative). These antibodies may reliably discriminate between clinically significant subtypes of RCC with overlapping cytoarchitectural features.

Review of tubulocystic carcinoma of the kidney with focus on clinical and pathobiological aspects

“…3A), and distal tubules/collecting ducts (cytokeratin 7, cytokeratin 19, keratin 903, and parvalbumin) (Fig. 3B) [10,13,17,[22][23][24]. The staining pattern of cytokeratin 7 may be weak and focal [10,15].…”

Mucinous tubular and spindle cell carcinoma of kidney and problems in diagnosis

“…The MTSCC diagnosis was made according to the 2004 WHO definition and the histopathological features of the cases defined afterwards (1,(10)(11)(12)(13)(14)(15)(16)(17). The main criteria were small elongated tubules and papillary structures separated by a pale mucinous stroma and spindle cells between the tubules.…”

Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma

“…[34][35][36] The percentage of PAX2 positivity reported in various types of renal cell carcinomas has ranged from 50 to 93% for clear cell, [34][35][36][37][38][39][40][41] 18 to 100% for papillary, 34,35,37,38,[40][41][42] and 6 to 83% for chromophobe. [35][36][37][38]40,41 It has also been reported to be frequently expressed in metastatic clear cell carcinomas (49-85%). 28,29,36,43,44 These results are comparable with those of the present investigation in which 7 (64%) of 11 primary and 16 (73%) of 22 metastatic clear cell, 6 (60%) of 10 papillary, and 4 (33%) of 12 chromophobe renal cell carcinomas were found to be PAX2 positive.…”

“…58 Because CA IX has been reported to be frequently expressed in renal cell carcinomas, especially the clear cell type, it is, at present, considered to be a diagnostic marker for clear cell renal cell carcinomas. [59][60][61][62][63][64] The percentage of CA IX reported in various types of renal cell carcinomas has ranged from 50 to 100% for clear cell, 35,41,[62][63][64][65][66][67][68] 23 to 100% for papillary, 35,41,62,64,66 and 0 to 31% for chromophobe. 35,41,62,64,66 It has also been reported to be frequently expressed in metastatic clear cell renal cell carcinomas (100%).…”