PAX-2 is a homeogene expressed during kidney development. Although immunohistochemical expression of PAX-2 has been described in a variety of primary renal cell carcinoma (RCC) subtypes and in metastatic RCC, its specificity as a marker of renal lineage in a metastatic setting has not been fully evaluated. In addition, its utility has not been directly compared with the most widely used antibody in this setting, renal cell carcinoma marker (RCCma). We studied PAX-2 expression in metastatic clear cell renal cell carcinoma (CC-RCC) and in a variety of nonrenal neoplasms with clear cytoplasm that may potentially mimic CC-RCC. Archival material from 27 CC-RCCs metastatic to various organs and 50 close morphologic mimics of CC-RCC were retrieved. Immunohistochemistry with PAX-2 and RCCmapi antibodies was performed on each case. Nuclear staining (PAX-2) or membranous staining (RCCma) was scored semiquantitatively. Twenty-three of 27 (85%) metastatic CC-RCCs showed nuclear immunoreactivity for PAX-2, whereas RCCma reactivity was found in 19 of 27 (70%). The immunoprofiles of the metastatic CC-RCC were PAX-2+/RCCma+: 19 of 27 (70%), PAX-2+/RCCma-: 5 of 27 (19%), PAX-2-/RCCma+: 2 of 27 (7%), and PAX-2-/RCCma-: 1 of 27 (4%). Five of the 50 mimics of CC-RCC (10%) had at least focal nuclear reactivity with PAX-2, including 1 of 3 parathyroid carcinomas (33%), 3 of 7 clear cell carcinomas of the ovary (43%), and the 1 clear cell papillary cystadenoma of the epididymis. Membranous RCCma reactivity was identified in 26 of the 50 mimics (52%). We conclude that PAX-2 is a useful marker for distinguishing metastatic CC-RCC from its potential morphologic mimics, but caution must be used in certain differential diagnostic settings where nonrenal tumors such as parathyroid carcinoma, ovarian clear cell carcinoma, and clear cell papillary cystadenoma of the epididymis were shown to express both PAX-2 and RCCma.

PAX-2, a homeogene expressed during kidney development, has been studied as a marker of renal origin in both primary and metastatic clear cell renal cell carcinoma (RCC), but not in papillary neoplasms or in comparison with RCC marker (RCCma). We studied immunohistochemical expression of PAX-2 and RCCma in 24 papillary RCC (PRCC) and 66 nonrenal cell papillary neoplasms (NRCPN) from a variety of organs. Of the PRCC, 16/24 (67%) were positive for PAX-2; 23/24 (96%) were positive for RCCma. Of the NRCPN, 9/66 (14%) is positive for PAX-2 [4/10 (40%) ovarian papillary serous carcinomas, 5/9 (56%) uterine papillary serous carcinomas]; RCCma was positive in 28/66 (42%), including 9/9 (100%) papillary thyroid carcinomas, 8/10 (80%) ovarian papillary serous carcinomas, 4/9 (44%) uterine papillary serous carcinomas, 1/10 (10%) papillary urothelial carcinomas, 1/2 (50%) intraductal papillary mucinous carcinomas of the pancreas, 3/3 (100%) choroid plexus papillomas, 1/1 (100%) pituitary adenoma with papillary features, and 1/2 (50%) lung adenocarcinomas with papillary features. The sensitivity of PAX-2+/RCCma+ immunophenotype for PRCC was 58% with a specificity of 54%. There is significant overlap between the expressions of these markers in PRCC and NRCPN; however, the positivity of RCCma and/or PAX-2 is 100% sensitive for PRCC and may prove useful in the initial work up of metastases of unknown primary. PAX-2 and RCCma immunohistochemistry should be interpreted with caution in papillary neoplasms, with particular attention to the possibility of ovarian and uterine papillary serous carcinomas, which can express both PAX-2 and RCCma.

Lipoprotein lipase (LPL)1 is a central enzyme in lipid metabolism and hydrolyzes the core of triglyceride-rich plasma lipoproteins into nonesterified fatty acids and monoacylglycerol (1). In adipose tissue and muscle, LPL is localized to the capillary endothelium, and contributes to the rapid removal of triglyceride-rich lipoproteins and their remnants.Catecholamines are of considerable physiologic importance in the mobilization of adipose tissue lipid in response to fasting and exercise. Hormones that cause elevated cAMP (␤-adrenergic agonists, ACTH, and glucagon) result in the activation of cAMP-dependent protein kinase A (PKA), which then activates hormone-sensitive lipase (HSL) (2, 3). HSL is the primary mediator of adipocyte lipolysis (4), and the release of nonesterified fatty acids from adipocytes play a central role in obesity and insulin resistance (5, 6). On the other hand, LPL hydrolyzes lipoproteins at the capillary endothelium generating nonesterified fatty acids for triglyceride storage. LPL and HSL serve opposing functions in adipose tissue, and they respond in an opposite fashion in response to hormonal regulation. In adipocytes, insulin and the fed state result in an increase in LPL activity along with a decrease in HSL activity, whereas hormones that are elevated during the fasting state, such as epinephrine and glucagon, inhibit LPL activity and stimulate HSL-mediated lipolysis (7-9).Although the decrease in LPL activity by catecholamines has been described previously (7), the cellular mechanisms controlling LPL inhibition are complex. In rat adipocytes, we found that the LPL synthetic rate was inhibited more than 5-fold within 30 min of addition of epinephrine to the medium, with no change in LPL mRNA levels (10). Studies of 3T3 adipocytes demonstrated that the inhibition of LPL translation by epinephrine involved an RNA-binding protein that interacted with the proximal 3Ј-untranslated region (UTR) of the LPL mRNA (11). Subsequent studies found the first 24 nucleotides of the LPL 3Ј-UTR essential for translational regulation, and a 30-kDa RNA-binding protein was identified by cross-linking as an important component of LPL translational regulation (12).This study was intended to identify the components involved in the translational regulation of LPL following cAMP elevation. As described below, we have identified the catalytic (C) subunit of PKA as the important 30-kDa protein involved in LPL translational regulation. However, the C subunit of PKA is likely part of an RNA binding complex, which also involves A kinase anchoring protein (AKAP) 121/149, which is involved in binding the PKA holoenzyme, and which contains a known RNA binding domain (13).

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