Adult ; Angiomyolipoma ; diagnosis ; genetics ; Exons ; genetics ; Humans ; Kidney Neoplasms ; diagnosis ; genetics ; Male ; Mutation ; genetics ; Tuberous Sclerosis ; complications ; Tuberous Sclerosis Complex 2 Protein ; genetics ; Young Adult

Store-operated calcium (Ca2+) entry (SOCE) is the principal Ca2+ entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients' outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC.
Adolescent ; Adult ; Aged ; Blotting, Western ; Carcinoma, Renal Cell/*diagnosis/metabolism/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kidney Neoplasms/metabolism/*pathology ; Male ; Middle Aged ; Neoplasm Proteins/genetics/metabolism ; ORAI1 Protein/genetics/*metabolism ; Prognosis ; Retrospective Studies ; Stromal Interaction Molecule 1/genetics/metabolism ; Young Adult

PURPOSE: Xp11.2 translocation renal cell carcinoma (RCC) is characterized by various translocations of the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults. Here, we review the clinicopathological features of Xp11.2 translocation RCC. MATERIALS AND METHODS: We identified 21 patients with Xp11.2 translocation RCC. We retrospectively analyzed patient characteristics, clinical manifestations, and specific pathological features to assess definitive diagnosis, surgical and systemic treatments, and clinical outcomes. RESULTS: The mean age at diagnosis was 43.4+/-20.0 years (range, 8-80 years; 8 males and 13 females). Eleven patients were incidentally diagnosed, nine patients presented with local symptoms, and one patient presented with systemic symptoms. The mean tumor size was 6.2+/-3.8 cm (range, 1.9-14 cm). At the time of diagnosis, 11, 1, and 5 patients showed stage I, II, and III, respectively. Four patients showed distant metastasis. At analysis, 15 patients were disease-free after a median follow-up period of 30.0 months. Four patients received target therapy but not effectively. CONCLUSIONS: Xp11 translocation RCC tends to develop in young patients with lymph node metastasis. Targeted therapy did not effectively treat our patients. Surgery is the only effective therapy for Xp11 translocation RCC, and further studies are needed to assess systemic therapy and long-term prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics ; Biomarkers ; Carcinoma, Renal Cell/diagnosis/*genetics ; Child ; Chromosomes, Human, X/*chemistry ; Female ; Humans ; Kidney Neoplasms/diagnosis/*genetics ; Lymphatic Metastasis ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Translocation, Genetic ; Young Adult

OBJECTIVETo study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion.

METHODSA total of 9 cases of such rare tumor were selected for clinicopathologic, immunohistochemical and molecular analysis, with review of literature.

RESULTSThe age of the patients ranged from 21 to 42 years (mean=31.3 years). The patients included four men and five women. Histologically, 4 of the 9 cases studied showed classic morphologic features of TFEB RCC, with hyaline material, pigments and psammoma bodies frequently identified. The remaining 5 cases demonstrated uncommon morphology, mimicking perivascular epithelioid cell neoplasm, clear cell RCC, chromophobe RCC or papillary RCC. Immunohistochemical study showed that TFEB and vimentin were positive in all cases. Most of the tumors studied also expressed Ksp-cadherin, E-cadherin, CD117, HMB45, Melan A and Cathepsin K. CKpan showed immunostaining in only 1 case. The staining for TFE3, CD10 and CK7 were all negative. TFEB gene rearrangement was detected in all the 9 cases studied using fluorescence in-situ hybridization. MALAT1-TFEB fusion gene was identified in 2 cases by polymerase chain reaction and direct sequencing. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none developed tumor recurrence, progression, or metastasis.

CONCLUSIONSTFEB fusion-associated RCC is a rare neoplasm, tends to occur in young age group and carries an indolent behavior. Diagnosis relies on clinicopathologic findings and immunohistochemical analysis. TFEB break-apart FISH assay is a reliable tool in confirming the diagnosis.

Adult ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Carcinoma, Renal Cell ; genetics ; pathology ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 6 ; Diagnosis, Differential ; Female ; Gene Fusion ; Gene Rearrangement ; Genes, Neoplasm ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kidney Neoplasms ; genetics ; pathology ; Male ; Prognosis ; RNA, Long Noncoding ; genetics ; Translocation, Genetic ; Young Adult

Accidents ; Adolescent ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; metabolism ; Carcinoma, Renal Cell ; genetics ; pathology ; surgery ; Chromosomes, Human, X ; Diagnosis, Differential ; Gene Fusion ; Humans ; Kidney ; injuries ; Kidney Neoplasms ; genetics ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Translocation, Genetic

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

Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide. Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease. Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical. RCC has been traditionally divided into clear-cell and non-clear-cell categories, with papillary RCC forming the most common subtype of non-clear-cell RCC. Renal neoplasms with overlapping histologies, such as tumors with mixed clear-cell and papillary features and hybrid renal oncocytic tumors, are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications. In this review, we discuss the histologic, immunohisto-chemical, cytogenetic, and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumor's microscopic appearance and its molecular fingerprint.
Biopsy, Large-Core Needle ; Carcinoma, Renal Cell ; classification ; diagnosis ; genetics ; pathology ; DNA Copy Number Variations ; DNA, Neoplasm ; genetics ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; classification ; diagnosis ; genetics ; pathology

Adenoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Carcinoma, Renal Cell ; genetics ; metabolism ; pathology ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Diagnosis, Differential ; Diploidy ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Retrospective Studies ; S100 Proteins ; metabolism ; Vimentin ; metabolism ; WT1 Proteins ; metabolism ; Wilms Tumor ; metabolism ; pathology

OBJECTIVETo investigate the expression of MN/CAIX in patients with renal cell carcinoma (RCC) and assess the value of MN/CAIX in the diagnosis of RCC.

METHODSRT-PCR was employed to detect MN/CAIX mRNA in the carcinoma tissue and peripheral blood of 62 patients with RCC, using normal renal tissue and peripheral blood sample from 32 patients without RCC as control. Immunohistochemistry was used to detect MN/CAIX protein in the tissue specimens of clear cell RCC (n=36), non-clear cell renal neoplasm (n=17) and normal kidney (n=16).

RESULTSThe positivity rate of MN/CAIX mRNA was 82.3% (51/62) in renal carcinoma tissues and 54.8% (34/62) in the peripheral blood from patients with RCC, significantly higher than the rates in the control cases (P<0.05). In cases of clear cell renal cell carcinoma, the positivity rate of MN/CAIX mRNA was 98% (49/50) in the carcinoma tissues and 66% (33/50) in the peripheral blood, significantly higher than the rates in cases of non-clear cell type of RCC (P<0.05). Immunohistochemistry showed a significantly higher positivity rate of MN/CAIX protein in clear cell RCC tissues [97.2% (35/36)] than in non-clear cell renal neoplasm and normal renal tissues (P<0.05).

CONCLUSIONMN/CAIX is specifically overexpressed in RCC, especially in clear cell RCC, suggesting its potential in the diagnosis and prognostic and therapeutic evaluation of RCC.

Adult ; Aged ; Antigens, Neoplasm ; genetics ; metabolism ; Biomarkers, Tumor ; Carbonic Anhydrase IX ; Carbonic Anhydrases ; genetics ; metabolism ; Carcinoma, Renal Cell ; diagnosis ; metabolism ; Female ; Humans ; Kidney Neoplasms ; diagnosis ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Young Adult

Adenoma, Acidophil ; metabolism ; Adult ; Angiomyolipoma ; genetics ; metabolism ; pathology ; Carcinoma, Renal Cell ; metabolism ; Codon ; Diagnosis, Differential ; Exons ; Female ; Follow-Up Studies ; Gene Deletion ; Genes, p53 ; Humans ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; Male ; Melanoma-Specific Antigens ; metabolism ; Middle Aged ; Retrospective Studies ; Tumor Suppressor Protein p53 ; genetics ; metabolism