Golgi glycoprotein 73(GP73) is a transmembrane glycoprotein residing in the cis-Golgi complex, which is strongly expressed in hepatocellular carcinoma (HCC) and secreted into the blood. It has been regarded as a promising serum tumor marker for the detection of HCC with higher sensitivity and specificity than AFP. GP73 is also significantly elevated in kidney cancer, prostate cancer, lung adenocarcinoma, esophageal cancer and seminomas; therefore, it would be helpful for the diagnosis of these diseases. However, the function of GP73 and the regulatory mechanism for its expression are unclear. In this article, the physical-chemical properties, the regulation of its expression, the relation with various cancers and the clinical applications of GP73 are reviewed.
Biomarkers, Tumor ; metabolism ; Humans ; Kidney ; metabolism ; Liver Diseases ; metabolism ; Membrane Proteins ; chemistry ; metabolism ; physiology ; Neoplasms ; diagnosis ; metabolism

OBJECTIVETo study the immunohistochemical expression of S100A1, GLUT-1 and Cavolin-1 and its diagnostic significance in renal tumors with oncocytic features.

METHODSTissue microarray and immunohistochemical staining for S100A1, GLUT-1 and Cavolin-1 were carried out in 59 cases of renal tumors with oncocytic features, including 19 cases of renal oncocytoma, 15 cases of clear cell renal cell carcinoma (CCRCC) with eosinophilic cells, 11 cases of eosinophilic variant of chromophobe renal cell carcinoma, 7 cases of oncocytic papillary renal cell carcinoma and 7 cases of epithelioid angiomyolipoma.

RESULTSS100A1 was expressed in renal oncocytoma, with a positive propotion of 16/19 (including 14 cases showing widespread and strong positivity). On the other hand, the rate of expression of S100A1 was 2/11 in eosinophilic variant of chromophobe renal cell carcinoma, 10/15 in CCRCC with eosinophilic cells, 3/7 in oncocytic papillary renal cell carcinoma and 6/7 in epithelioid angiomyolipoma (P>0.05). The difference of S100A1 expression between renal oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma was statistically significant. GLUT-1 was located in cell membrane, with a positive rate of 13/15 in CCRCC with eosinophilic cells, 7/19 in renal oncocytoma, 4/7 (weak) in oncocytic papillary renal cell carcinoma, 1/11 in eosinophilic variant of chromophobe renal cell carcinoma and 0/7 in epithelioid angiomyolipoma. The rate of expression of Cav-1 was 6/15 in CCRCC with eosinophilic cells, 2/7 in oncocytic papillary renal cell carcinoma, 5/7 in epithelioid angiomyolipoma, 2/11 (weak) in eosinophilic variant of chromophobe renal cell carcinoma and 0/19 in renal oncocytoma. S100A1 showed high sensitivity and 50% specificity in the diagnosis of renal oncocytoma. GLUT-1 and Cav-1 showed high specificity and sensitivity in the diagnosis of CCRCC and epithelioid angiomyolipoma.

CONCLUSIONSS100A1 is widely expressed in various oncocytic renal neoplasms and helpful in differential diagnosis of renal oncocytoma from eosinophilic variant of chromophobe renal cell carcinoma, but not from other 3 oncocytic renal tumors. Overexpression of GLUT-1 can be used in distinction between CCRCC and renal oncocytoma. Cav-1 is widely expressed in CCRCC and epithelioid angiomyolipoma but not in renal oncocytoma. Cav-1 expression thus rules out renal oncocytoma.

Adenoma, Oxyphilic ; diagnosis ; metabolism ; Angiomyolipoma ; diagnosis ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Renal Cell ; diagnosis ; metabolism ; Caveolin 1 ; metabolism ; Diagnosis, Differential ; Glucose Transporter Type 1 ; metabolism ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; diagnosis ; metabolism ; S100 Proteins ; metabolism ; Sensitivity and Specificity

Adenocarcinoma, Follicular ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Carcinoma, Renal Cell ; genetics ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Kidney Diseases, Cystic ; genetics ; metabolism ; pathology ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; Translocation, Genetic

Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Cytokines ; metabolism ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Kidney ; chemistry ; pathology ; surgery ; Kidney Diseases, Cystic ; metabolism ; pathology ; surgery ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Nephrectomy

12E7 Antigen ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Nephrectomy ; Osteosarcoma ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Aged ; Angiomyolipoma ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Leiomyoma ; metabolism ; pathology ; Lymphocytes ; pathology ; Male ; Nephrectomy ; Neurilemmoma ; metabolism ; pathology ; surgery ; S100 Proteins ; metabolism

Adenocarcinoma, Follicular ; Adult ; Carcinoid Tumor ; metabolism ; pathology ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Keratin-7 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Mucin-1 ; metabolism

OBJECTIVETo study the expression of a novel marker, kidney-specific-protein (Ksp)-cadherin, in renal epithelial neoplasms and its clinicopathologic significance.

METHODSImmunohistochemical study (using EnVision method) for Ksp-cadherin, CD10, vimentin, epithelial membrane antigen and CK7 was carried out in normal human kidney samples, as well as in 166 cases of primary renal neoplasms (including 120 cases of clear cell renal cell carcinoma (RCC), 20 cases of papillary RCC (type I papillary RCC 15 cases and type II papillary RCC 5 cases), 18 cases of chromophobe RCC and 8 cases of oncocytoma).

RESULTSKsp-cadherin was expressed in distal convoluted tubules of normal kidney in a membranous pattern. It was also detected in 23% (27/120) of clear cell RCC, 20% (4/20) of papillary RCC, 100% (18/18) of chromophobe RCC and 75% (6/8) of oncocytoma. High expression of CD10 and vimentin was noted in clear cell RCC and papillary RCC. CD10 was also expressed in chromophobe RCC in cytoplasmic pattern, compared with membranous staining in the other tumors. CK7 expression was mainly seen in chromophobe RCC and papillary RCC, while epithelial membrane antigen was expressed in all variants of RCC. On the other hand, the expression of Ksp-cadherin in clear cell RCC correlated with tumor stage and grade.

CONCLUSIONSKsp-cadherin is expressed in normal distal convoluted tubules and the related neoplasms. It carries relatively high specificity and sensitivity in diagnosis of chromophobe RCC and oncocytoma. The expression of Ksp-cadherin also correlates with biologic behavior of clear cell RCC.

Adenoma, Oxyphilic ; metabolism ; pathology ; Cadherins ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; metabolism ; pathology ; Kidney Tubules ; metabolism ; pathology ; Neoplasm Staging ; Neprilysin ; metabolism ; Vimentin ; metabolism

Claudin-7 has recently been suggested to be a distal nephron marker. We tested the possibility that expression of claudin-7 could be used as a marker of renal tumors originating from the distal nephron. We examined the immunohistochemical expression of claudin-7 and parvalbumin in 239 renal tumors, including 179 clear cell renal cell carcinoma (RCC)s, 29 papillary RCCs, 20 chromophobe RCCs, and 11 renal oncocytomas. In addition, the methylation specific-PCR (MSP) of claudin-7 was performed. Claudin-7 and parvalbumin immunostains were positive in 3.4%, 7.8% of clear cell RCCs, 34.5%, 31.0% of papillary RCCs, 95.0%, 80.0% of chromophobe RCCs, and 72.7%, 81.8% of renal oncocytomas, respectively. The sensitivity and specificity of claudin-7 in diagnosing chromophobe RCC among subtypes of RCC were 95.0% and 92.3%. Those of parvalbumin were 80.0% and 88.9%. The expression pattern of claudin-7 was mostly diffuse in chromophobe RCC and was either focal or diffuse in oncocytoma. All of the cases examined in the MSP revealed the presence of unmethylated promoter of claudin-7 without regard to claudin-7 immunoreactivity. Hypermethylation of the promoter might not be the underlying mechanism for loss of its expression in RCC. Claudin-7 can be used as a useful diagnostic marker in diagnosing chromophobe RCC and oncocytoma.
Tumor Markers, Biological/metabolism ; Tumor Cells, Cultured ; Tissue Distribution ; Sensitivity and Specificity ; Reproducibility of Results ; Nephrons/metabolism ; Neoplasm Proteins/metabolism ; Membrane Proteins/analysis/*metabolism ; Kidney Neoplasms/*diagnosis/*metabolism ; Humans ; Carcinoma, Renal Cell/*diagnosis/*metabolism ; Adenoma, Oxyphilic/*diagnosis/*metabolism

Adenoma, Oxyphilic ; metabolism ; pathology ; surgery ; Cadherins ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Catheter Ablation ; Diagnosis, Differential ; Humans ; Keratins ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Parvalbumins ; metabolism ; S100 Proteins ; metabolism