Amylase α-1A (AMY1A): a novel immunohistochemical marker to differentiate chromophobe renal cell carcinoma from benign oncocytoma.

Chromophobe renal cell carcinoma (ChRCC) and oncocytoma are distinct renal tumors with a proposed common cell of origin: the intercalated cell of the collecting duct. Classic histopathology of ChRCC and oncocytoma are readily distinguishable; however, not uncommonly, some of these renal tumors may present with a perplexing overlap of morphologic and immunohistochemical (IHC) features. The eosinophilic variant of ChRCC is one such example in which the abundance of smaller, eosinophilic cells mimics oncocytoma. Despite the pathologic overlap of these 2 tumors, their biological behavior and clinical outcomes are significantly different, which is why it is important to distinguish them. Oncocytoma is a benign tumor and despite microscopic extension into perinephric adipose tissue and vascular invasion, which occur infrequently, has a low mortality of 0%.1–3 ChRCC is a malignant tumor with a higher mortality rate. The majority of ChRCC cases present with stage T1 and T2 disease (86%). Only 10% of ChRCC cases show extracapsular extension, and only 4% show renal vein involvement.4 Several IHC markers have been investigated to distinguish these 2 tumors such as LMP2, parvalbumin, cytokeratin 7 (CK7), MOC-31, cadherin, caveolin-1, c-kit, claudin-7 and 8, MAGE-A3/4, NYES0-1, and S100A1.5–13 Unfortunately, no single marker or panel of biomarkers conclusively aids in this distinction. In a recent study from our institution, copy number variations across different types of renal neoplasms were analyzed using high-resolution single nucleotide polymorphism arrays.14 Interestingly, all ChRCC cases were found to exclusively share common deletions in the 1p21.1 region that includes the AMY1A gene. No such deletions were found in oncocytoma. Instead, oncocytomas shared other deletions on chromosome 1: 1p31.3, 1q25.2, and 1q44. Four of 5 clear cell tumors had deletions of the entire coding region of the amylase 1A gene. Two of the papillary tumors had a complete deletion as well, whereas the remaining had deletions dispersed throughout the AMY1A gene domain; a single exon deletion can prevent assembly of a functional transcript. Human α-amylases (α-1, 4-glucan 4-glucanohydrolase, E. C. 3. 2.1.1) are mainly produced in the salivary gland and pancreas. Among the several amylase genes that are expressed at high levels in either the salivary gland or the pancreas, AMY1A gene encodes the salivary gland–type amylase isoenzyme that hydrolyzes the 1,4-α-glucoside bonds in oligosaccharides and polysaccharides to produce maltose, which is cleaved to 2 molecules of glucose by enzyme maltase.15 Amylase enzyme (mainly salivary type) is also produced in some malignant tumors, viz., lung cancer, ovarian cancer, plasmacytoma, normal thyroid tissue, thyroid adenomas, and cancer.16–19 The aim of this study was to examine the utility of Amy1A in distinguishing between oncocytoma and ChRCC.