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

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 ; diagnosis ; metabolism ; Carcinoma, Renal Cell ; diagnosis ; metabolism ; Humans ; Immunohistochemistry ; methods ; Keratins ; analysis ; Kidney Neoplasms ; diagnosis ; metabolism ; Proto-Oncogene Proteins c-kit ; analysis ; Sensitivity and Specificity ; WT1 Proteins ; analysis ; Wilms Tumor ; 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

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

OBJECTIVETo study the expression of carbonic anhydrase IX (CAIX), PAX2 and PAX8 in different types of renal epithelial tumor and their association with clinicopathologic characteristics.

METHODSImmunohistochemical study by EnVision method was performed in order to assess the expression of CAIX, PAX2 and PAX8 in 155 cases of renal cell carcinoma and 4 cases of metastatic clear cell renal cell carcinoma (CCRCC). Ninety-six cases of non-neoplastic renal parenchymal tissue adjacent to CCRCC, 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma were used as controls.

RESULTSCAIX was commonly expressed in CCRCC (94.0%, 63/67), of which 77.8% (49/63) showed strong positivity. CAIX was focally positive in papillary renal cell carcinoma, collecting duct carcinoma and urothelial carcinoma of renal pelvis. It was negative in chromophobe renal cell carcinoma, oncocytoma and adjacent non-neoplastic renal tissue. CAIX was also strongly expressed in the 4 cases of metastatic CCRCC. Focal expression of CAIX was demonstrated in the 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma. The expression of CAIX in CCRCC did not correlate with tumor grading, clinical staging and presence of distal metastasis. On the other hand, PAX2 showed positive expression in different types of renal epithelial tumor, clear cell hepatocellular carcinoma and clear cell hidradenoma in various degrees. In contrast, PAX8 was commonly expressed in all types of renal epithelial tumor, with the exception of urothelial carcinoma of renal pelvis. PAX8 was not expressed in clear cell hepatocellular carcinoma and clear cell hidradenoma. Regarding diagnosis of CCRCC, CAIX demonstrated high sensitivity and specificity. PAX2 showed high specificity but low sensitivity. PAX8 was sensitive and specific in the diagnosis of renal epithelial tumor.

CONCLUSIONSCAIX is a useful immunohistochemical marker with high specificity and sensitivity in distinguishing CCRCC from other types of renal epithelial tumor and clear cell tumors of non-renal origin. PAX2 is a marker with high sensitivity and low specificity for diagnosis of renal epithelial tumors. PAX8 is typically expressed in renal epithelial tumors. The combined detection of CAIX, PAX2 and PAX8 is useful in the diagnosis and differential diagnosis of renal epithelial tumors.

Adenoma, Oxyphilic ; metabolism ; pathology ; Antigens, Neoplasm ; metabolism ; Carbonic Anhydrase IX ; Carbonic Anhydrases ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; Male ; PAX2 Transcription Factor ; metabolism ; PAX8 Transcription Factor ; Paired Box Transcription Factors ; metabolism

Adenocarcinoma, Follicular ; metabolism ; pathology ; Adenoma, Chromophobe ; metabolism ; pathology ; Adenoma, Oxyphilic ; metabolism ; pathology ; Angiomyoma ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Carcinoma, Papillary ; metabolism ; pathology ; Carcinoma, Renal Cell ; classification ; metabolism ; pathology ; ultrastructure ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; classification ; metabolism ; pathology ; ultrastructure ; Thyroid Neoplasms ; metabolism ; pathology

OBJECTIVETo study the clinicopathologic features, immunohistochemical profiles and prognosis of chromophobe renal cell carcinoma (ChRCC).

METHODSForty-two cases of ChRCC were retrieved from the archival files of the Affiliated Hospital of Qingdao University, 401 Hospital of PLA and Qingdao Municipal Hospital from 2003 to 2011. The clinical and pathologic features of the tumors were reviewed. Hale colloidal iron staining was performed and EnVision immunohistochemistry was used to detect the expression of a series of immunologic markers. Forty cases of clear cell renal cell carcinoma and 10 cases of renal oncocytoma were selected as controls.

RESULTSThe patients included 17 males and 25 females. The age of patients ranged from 39 years to 78 years (median age = 57 years). On gross examination, the tumors ranged from 2 cm to 19 cm in greatest dimension (mean size = 7.3 cm). Histologically, the tumors were mainly composed of solid sheets, acini or tubules of malignant cells. The tumor cells contained clear finely reticular ("chromophobe") and eosinophilic cytoplasm with perinuclear clearing. The nuclear outline was irregular and wrinkled. Nucleoli were inconspicuous and mitotic figures were barely seen. Hale colloidal iron stain was positive in all cases. Immunohistochemically, the tumor cells were variably positive for EMA (100%, 42/42), CK7 (95.2%, 40/42), Ksp-cad (92.9%, 39/42), CK18 (88.1%, 37/42), CD117 (61.9, 26/42), CD10 (31.0%, 13/42) and PAX2 (28.6%, 12/42). They were negative for vimentin, CA IX and TFE3. The follow-up period in 31 patients ranged from 2 to 77 months (average duration = 29 months). Three patients died of tumor metastasis 3, 8, 13 months respectively after the operation. Twenty-eight patients were still alive without evidence of tumor recurrence.

CONCLUSIONSChRCC predominantly occurs in middle-aged and elderly patients. It often carries a favorable prognosis. The presence of plant cell-like morphology, pale cells with uniform reticular microvesicular appearance and perinuclear clearing are characteristic histologic features. The diffuse positivity for Hale colloidal iron stain and EMA/CK7/Ksp-cadherin/CD117-positive immunoprofiles are also useful in differential diagnosis.

Adenoma, Oxyphilic ; metabolism ; pathology ; Adult ; Aged ; Cadherins ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Immunophenotyping ; Keratin-18 ; metabolism ; Keratin-7 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Nephrectomy ; methods ; Treatment Outcome