Expression of Renal Cell Carcinoma Antigen (RCC) in Renal Epithelial and Nonrenal Tumors

Abstract

Antibody to renal cell carcinoma (RCC) antigen, a normal human proximal brush border antigen, has recently become commercially available and reported to be highly specific and a relatively sensitive marker for RCC. Of the nonrenal tumors occasional carcinomas have been reported to express RCC, notably breast carcinoma. Using tissue microarrays, we investigated the use of RCC on a large number of renal epithelial neoplasms (RENs) and nonrenal tumors, especially those potentially confused with REN. Three tissue microarrays containing 241 REN samples, 192 samples of a wide variety of neoplasms and 170 adrenal tumor samples, respectively, were stained with RCC monoclonal antibody. RCC expression was scored for staining intensity and percentage expression. Out of 241 REN, 173 were positive for RCC (sensitivity 72%): clear cell 72%, papillary 95%, chromophobe 91%, unclassified 85%, oncocytoma 75%, sarcomatoid 20%, and metastatic RCC 40%. The overall immunostaining intensity was consistently much higher in papillary and clear cell RCC than in other tumors. Seventy-six out of 362 nonrenal tumor samples demonstrated either focal or diffuse expression for RCC (specificity 79%). These included: adrenocortical neoplasms 37/170 (22%), colonic 11/29 (37.5%), breast 9/27 (33%), prostate 5/18 (27.7%), ovary 2/17 (11.7%), melanoma 3/18 (16.6%), lung 3/21 (14.2%), and parathyroid 3/3 (100%). RCC expression was seen equally among adrenal adenoma and carcinoma group. Eight out of 28 (28.5%) normal adrenal cores also stained for RCC. RCC is a relatively useful marker in the differential diagnosis of REN only if used in a panel with other positive and negative markers. RCC does not reliably differentiate REN, especially classic clear cell type, from adrenocortical neoplasms, which are frequently confused due to close anatomic proximity and similar morphology. RCC also does not reliably differentiate subtypes of renal epithelial neoplasms.

Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study

“…In addition, most of these proteins were later found not to be as specific as initially claimed. [12][13][14] In contrast, the cell-lineage-specific transcription factors are expressed much earlier during the development and most of them are the 'initiators' of specific cellular differentiation. They appear before the terminal differentiation proteins and are more frequently detected in poorly differentiated tumors.…”

“…33 The differences in embryonic origins and functions in the different segments of nephron may have contributed to the diversity of morphologic patterns, molecular, and immunohistochemical phenotypes of common renal epithelial tumors. 34 On account of these variable features and the absence of renal-specific positive markers, 13 a panel of immunohistochemical markers is always required to substantiate the diagnosis and classification of renal epithelial tumors. Therefore, renal-specific immunohistochemical markers are of great diagnostic interest.…”

“…7 On account of its diverse histologic features, metastatic RCC can be a diagnostic challenge and frequently requires ancillary tests, such as immunohistochemistry, for confirmation. 8 Many makers including cytokeratins (CK), CK7, CK20, EMA, vimentin, 9 c-kit, 10 P504S, 11 RCCmarker, 12,13 aquaporin-1, 14 CD10, 15 and carbonic anhydrase 9 (CAIX) 16,17 have been used in various panels with variable sensitivity and specificity.…”

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

“…71 Although RCC Ma expression has been reported in all types of renal cell carcinomas, it is more frequently expressed in clear cell (B40-85%) 10,71-77 and papillary (B50-95%) 40,42,72,74,[76][77][78][79] renal cell carcinomas. This marker has also been reported in a large percentage of metastatic renal cell carcinomas (B40-85%).…”

“…This marker has also been reported in a large percentage of metastatic renal cell carcinomas (B40-85%). 43,68,71,75,76,79 It should be emphasized, however, that RCC Ma is not absolutely specific for these tumors as it can be expressed in other malignancies, including embryonal carcinomas, 74,80 adenocarcinomas of the breast, 71,74,76 prostate and colon, 76 adrenal cortical carcinomas, 76 and mesotheliomas. 10,75 Only two studies have been published on RCC Ma expression in mesotheliomas.…”