The Immunohistochemical Distinction between Clear-Cell Renal-Cell Carcinoma and Other Forms of Clear-Cell Carcinoma
Scott M Wendroth, Mark J Mentrikoski, Mark R Wick. University of Virginia, Charlottesville, VA
Background: It is well-known that clear-cell renal-cell carcinoma (CC-RCC) has the ability to metastasize throughout the body, and to imitate the clear-cell variants of many other tumors morphologically. Thus, immunostains are often required to discriminate between such lesions. Despite the availability of several markers for CC-RCC, their individual sensitivities and specificities for that tumor are variable. This study was designed to assess the relative diagnostic values of commonly-used potential labels for CC-RCC (PAX2, PAX8, CD10, RCC-Ag, and adipophilin [ADP]) in its separation from other clear-cell carcinomas of non-renal origin. CA125 stains were also performed to aid in the distinction between renal and Mullerian neoplasms.
Design: Fifty-one non-renal clear-cell carcinomas and 26 examples of CC-RCC were retrieved from the authors' institutional archives. The non-renal tumors included carcinomas of breast, liver, lung, vagina, cervix, urinary bladder, salivary gland, ovary, skin, and lung. Immunostaining for the specified determinants was performed on each specimen using standard methods and an automated platform. Staining results were simply recorded as either positive (immunoreactivity in > 5% of tumor cells) or negative. Intensity of labeling was graded as 1 to 3+. The sensitivity and specificity of each stain, vis-à-vis the diagnosis of CC-RCC, was then calculated using Bayesian methods.
Results: The overall sensitivity of CD10, ADP, RCC-Ag, PAX2, and PAX8 for the diagnosis of CC-RCC was 85%, 100%, 72%, 81%, and 100%, respectively. Respective individual specificities were 74%, 52%, 100%, 73%, and 60%. Analytic exclusion of mullerian tumors (from vagina, cervix, and ovary) enhanced the specificities of PAX (to 97%) and PAX8 (to 89%), while decreasing the specificities of CD10 (to 68%) and ADP (to 47%). CA125 was not expressed in any CC-RCC cases, but it was sensitive and specific for the identification of mullerian neoplasms, with respective results of 81% and 93%.
Conclusions: No individual immunohistologic marker in this study was both optimally sensitive and specific for the diagnosis of CC-RCC, thus confirming the need for a moderately-sized panel of analytes in the differential diagnosis of that neoplasm. PAX2 and PAX8 show excellent specificity for CC-RCC, but they have lesser contextual value in women patients because of potential shared reactivity in mullerian tumors. In those cases, CA125 is an effective additional marker that discriminates between lesions of the kidneys and the female genital tract.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 87, Tuesday Morning