Overexpression of Glutathione S-Transferase α in Clear Cell Renal Cell Carcinoma

Abstract

To determine its diagnostic value, we evaluated glutathione S-transferase alpha (GST-alpha) expression in a large number of renal cell carcinomas (RCCs). GST-alpha messenger RNA (mRNA) levels from 70 renal neoplasms were analyzed with complementary DNA (cDNA) microarray chips containing 21,632 cDNA clones. Furthermore, 348 primary renal tumors and 24 metastatic RCCs were subjected to immunohistochemical analysis with a GST-alpha-specific antibody. GST-alpha mRNA was elevated significantly (11.4-fold) in a majority of clear cell RCCs (28/43 [65.1%]; 28/39 [71.8%] with adjustments for informative spots) compared with other kidney tumors (1/27 [3.7%]). Strong and diffuse GST-alpha immunoreactivity was demonstrated in a majority of clear cell (166/202 [82.2%]; mean intensity, 2.41) and metastatic clear cell RCCs (17/24 [70.8%]; mean intensity, 2.62). Other renal tumor types did not exhibit significant GST-alpha immunoreactivity, confirming mRNA results. Through cDNA microarrays and immunohistochemical analysis, we demonstrated GST-alpha as a biomarker for clear cell RCCs.

Immunohistochemical marker panel differentiates between the three most common subtypes of renal cell carcinoma independent from histomorphologic criteria

“…b Sensitivity and specificity for both markers resulted in LR+ <10 and LR->0.1 Table 2 Review of the six marker combination for each single specimen; positive staining for each marker scored +1 for the respective subtype RCC main subtypes as described in the literature, although the differences between the subtypes were occasionally not as pronounced. For example, sensitivity for GST-α and CD-10 in terms of cc-RCC was comparable to the published data [6][7][8][9][10]13]; however, a number of pp-RCC and cp-RCC tumors expressed GST-α and CD10, respectively. Consequently, specificity of these markers was affected and lower than that reported in earlier studies [7,13,15].…”

“…For example, sensitivity for GST-α and CD-10 in terms of cc-RCC was comparable to the published data [6][7][8][9][10]13]; however, a number of pp-RCC and cp-RCC tumors expressed GST-α and CD10, respectively. Consequently, specificity of these markers was affected and lower than that reported in earlier studies [7,13,15]. This might be attributed to the increased number of papillary and especially chromophobe RCC tumors in our study [8-10, 14, 25].…”

“…Although our findings verified this observation, both markers are reported to be expressed to a higher extent in literature, reaching values up to100% for C-KIT [20][21][22][23] and Parvalbumin [7,16]. However, LR+ for detection of cp-RCC by C-KIT was still 34.7.…”

“…cc-RCC is frequently associated with high expression of GST-α [6,7] and CD10 [8][9][10][11][12]. Both markers are already in use to differentiate the most common subtypes in RCC [5,11,13].…”

Glutathione S-transferase polymorphisms: cancer incidence and therapy

“…Epidemiological results show that aberrant expression of GSTa has been linked to an increased risk in colorectal cancer, ovarian cancer and clear cell renal cell carcinoma ; Tetlow et al, 2004a;Chuang et al, 2005).…”