A subset of renal cortical tumors cannot be accurately classified based on their morphologic features owing to partial overlap in their histologic appearance. Since the prognosis is different and clear cell carcinomas may be treated by the different therapeutic regimens there is a need for accurate classification.
A number of markers have been tested to assist in this task, but even when several markers are used a significant number of tumors remain unclassifiable. Carbonic anhydrase IX (CA IX) plays an important role in maintaining the pH of several tumor types. It is a stable cell surface protein that is amenable for detection by immunohistochemistry. CA IX has been found to be expressed in clear cell renal cell carcinoma (RCC) and type 1 papillary renal cell carcinoma. In this study, we have investigated the expression pattern of CA IX in 44 papillary RCC, 42 clear cell RCC, 37 chromophobe RCC and 28 oncocytomas.
The majority (95%) of clear cell RCC were positive, whereas only two cases (5%) of papillary RCC showed focal positivity. All chromophobe RCC and oncocytoma were negative. Immunohistochemistry for CA IX can be easily performed and positive staining in the absence of papillary features strongly suggest clear cell RCC.
Renal cortical tumors can be classified according to their histologic appearance and/or genetic abnormalities.1, 2 A minority (5%) of tumors cannot be typed owing to overlap in their morphologic features and to a lesser degree also in their genetic alterations.2, 3 Accurate classification is important since different tumors have different prognosis and clear cell carcinomas may be treated differently.
Furthermore, the increased use of core biopsy to diagnose small tumors that are ablated at the time the biopsy is performed and tumors of patients who are poor surgical candidates increases the need for accurate typing on limited amounts of tissue. Commonly used antibodies including cytokeratin AE1/AE3, Pax-2, PAX-8, CK7, CK20, RCC, CD10, and vimentin can be helpful but do not provide definitive answer in a subset of cases.4–7
Recently, a new antibody became available for studying carbonic anhydrase IX (CA IX) expression in formalin fixed paraffin embedded tissue sections. Carbonic anhydrases are widely expressed in living organisms including in mammalian cells with 15 recognized isoenzymes.8–11 They catalyze reversible hydration of carbon dioxide (H2O + CO2 = H+ + HCO3) that results in a net extrusion of H+ and an increase in intracellular pH. The maintenance of pH during hypoxia is a key protective mechanism to prevent hypoxia induced cell death. Hypoxia upregulates the activity of a number of genes through hypoxia inducible factor-1alpha (HIF-1alpha) including two carbonic anhydrases (CA IX and CA XII).8–11 CA IX is a 54/58 KDa transmembrane glycoprotein that has a cell surface enzyme activity and can be detected in normal gastrointestinal mucosa and a number of different tumors.
In the kidney, CA IX overexpression has been described in clear cell renal cell carcinoma and in type 1 papillary renal cell carcinoma but not in normal renal tissue.10–11 In this study, our aim was to investigate the expression patterns of CA IX in the most common types of renal cortical neoplasms and to determine whether CA IX expression can be helpful for differentiating these tumor types.
Figure 1. CA IX immunohistochemistry of Clear cell renal cell carcinoma.
Materials and Methods
Five micron sections of previously constructed tissue microarrays (