Differential expression of caveolin‐1 in renal neoplasms

Abstract

BACKGROUND.Caveolin‐1 is a major component of membrane caveolae, which are specialized lipid raft microdomains on cell membrane that are implicated in molecular transport, cell adhesion, and signal transduction. The overexpression of caveolin‐1 recently was associated with a poor outcome in patients with clear‐cell renal cell carcinoma (CCRCC) and was proposed as a useful diagnostic marker. In the current study, the authors used immunohistochemistry to investigate the membranous and cytoplasmic expression of caveolin‐1 and its correlation with other pathologic parameters in different subtypes of renal neoplasms.METHODS.A tissue microarray (TMA) was constructed from 60 normal kidneys, 22 CCRCCs, 20 papillary renal cell carcinomas (PRCCs), 16 chromophobe renal cell carcinomas (ChRCCs), and 19 oncocytomas (ONCs). The TMA was immunostained for caveolin‐1 protein. Both membranous and cytoplasmic caveolin‐1 expression levels were measured and were correlated with tumor size, Fuhrman nuclear grade, and pathologic stage.RESULTS.Caveolin‐1 was expressed normally in distal convoluted tubules, collecting ducts, parietal cells of Bowman capsule, smooth muscle, and vascular endothelial cells. Membranous caveolin‐1 expression was detected in 19 of 22 CCRCCs (86.4%), which was significantly higher than the membranous caveolin‐1 expression detected in PRCCs (1 of 20 tumors; 5%), ChRCCs (0 of 16 tumors; 0%), and ONCs (1 of 19 tumors; 5.3%). Cytoplasmic caveolin‐1 expression was detected in 16 of 22 CCRCCs (72.7%), in 13 of 20 PRCCs (65%), in 8 of 16 ChRCCs, (50%), and in 13 of 19 ONCs (68.4%). The percentage of tumors that expressed cytoplasmic caveolin‐1 did not differ significantly among the different types of renal tumors (P = .1). Only membranous caveolin‐1 expression was correlated with tumor size (Pearson correlation = 0.266; P = .043). There was no correlation between membranous or cytoplasmic caveolin‐1 expression and other pathologic parameters, including Fuhrman nuclear grade and staging according to the American Joint Committee on Cancer tumor, lymph node, metastasis classification system.CONCLUSIONS.Caveolin‐1 expression has 2 distinctive patterns in renal neoplasms: membranous and cytoplasmic. In the current study, membranous caveolin‐1 expression was detected predominantly in CCRCCs and only rarely in other subtypes of renal neoplasms. Thus, the current results indicated that caveolin‐1 expression may have potential both as a diagnostic marker in the differential diagnosis of renal tumors and as a therapeutic target, especially for CCRCC. Cancer 2007. © 2007 American Cancer Society.

Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

“…Therefore, it is envisaged that their incorporation within similar combined staging systems for RCC as described above will further improve the predictive power of such models. Interestingly, a subset analysis of our RCC cohort revealed that the expression of caveolin-1 was invariably absent or minimal within papillary carcinomas; an observation in agreement with Tamaskar et al (2007). However, high expression of pAKT, pmTOR, pS6 and p4E-BP1 was evident in these papillary tumours.…”

Hypoxia promotes ligand-independent EGF receptor signaling via hypoxia-inducible factor–mediated upregulation of caveolin-1

“…The direct link between CAV1 and HIF presented herein likely explains why, in various tumors including CCRCC, CAV1 overexpression, similar to HIFα, is associated with larger tumor size, higher tumor grade and stage, resistance to conventional therapies, and poor prognosis (10)(11)(12)(13)(14)(15)44). Consistent with this notion, primary CCRCC cells with a strong hypoxic signature exhibited elevated expression of CAV1 and phosphorylated ERK levels, and molecular suppression of CAV1 attenuated Ras-(C)Raf-MEK-ERK signaling, cell proliferation, and migratory capacity in the absence of ligand.…”

“…CAV1, through scaffolding domains (CSD), also has been shown to bind several proteins involved in signaling (8). Intriguingly, similar to HIFα, elevated CAV1 expression has been associated with larger tumor size, higher tumor grade and stage, resistance to conventional therapies, and poor prognosis in numerous cancer types in several organs, including colon, liver, stomach, prostate, breast, lung, brain, and kidney (but with the exception of extrahepatic bile duct carcinoma and mucoepidermoid carcinoma of the salivary gland, in which increased CAV1 expression has been correlated with favorable clinical outcome) (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Although these observations suggest a possible correlation between HIF and CAV1, the molecular mechanisms regulating CAV1 expression and CAV1-mediated signaling remain largely unknown.…”

Fibronectin 1 protein expression in clear cell renal cell carcinoma

“…A significant increase in its incidence has been observed during the last few decades, and the annual mortality-to-incidence ratio for RCC is considerably higher than for other tumors of the genitourinary tract (1). RCC encompasses numerous histological subtypes with distinct genetic and biological features that determine clinical course and outcome (2). Tumor characteristics such as tumor stage and grade appear to have limited value in predicting the clinical outcome of individual patients, as approximately 50% of patients who undergo surgery with curative intent for less advanced disease are expected to develop a distant recurrence.…”