Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight histologically-confirmed cases of clear cell sarcoma of the kidney (CCSK) were studied for possible mutations in the p53 tumor suppressor gene by the immunohistochemical demonstration of mutant p53 proteins using a monoclonal (DO7: Dako) and a polyclonal (AB565: Chemicon) antibody to p53 protein. All cases exhibited p53 protein nuclear immunopositivity, although in varying numbers of tumor cells and with different staining intensities. p53 protein (DO7 or AB565) was expressed in < 25% of the tumor cells in four (50%) of the cases, including the one case with a known long term survival of 13 years from the time of diagnosis. The other tumors showed p53 protein immunopositivity in > 25% of the tumor cells when stained with either DO7 or AB565 or both. The intensity of staining, graded on visual impression into weak, moderate or strong, did not correlate well with the ratio of positive staining tumor cells. While this study is unable to clarify the relative prevalence and importance of p53 mutational events in the pathogenesis of this aggressive renal tumor of childhood, it is reasonably suggestive that alterations in the p53 tumor suppressor gene do occur in CCSK.
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PMID:Implications of p53 protein expression in clear cell sarcoma of the kidney. 891 50

Childhood kidney tumors seldom metastasize into the cranial cavity unless it is a special histological variant. We report a 4-year-old boy with multiple intracranial metastases in the left parietotemporal and right cerebellar area from primary clear cell sarcoma of the kidney without evidence of bony metastases. Metastatic tumor revealed nests of uniformly polygonal cells with clear cytoplasm demarcated by delicate fibrovascular arcades. Tumor cells were positive for vimentin and negative for cytokeratin, S-100 protein, desmin, and myoglobin. Cellular proliferation rate measured by PCNA, and Ki-67 was not significantly different between primary tumor mass and metastatic brain lesion. Expression of p53 oncoprotein was not evident in both lesions. These findings suggested that the relapse and metastasis of clear cell sarcoma of the kidney was probably due to regrowth of micro-metastases which were present at an early stage of disease.
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PMID:Intracranial metastasis from clear cell sarcoma of the kidney--a case report. 936 10

We reviewed 351 cases of clear cell sarcoma of the kidney (CCSK), including 182 cases entered on National Wilms Tumor Study Group (NWTSG) trials 1-4 for which clinical follow-up information was available. Tumors were restaged using NWTS 5 criteria. Mean age at diagnosis in the NWTS group was 36 months with a range of 2 months to 14 years. The male to female ratio was 2:1. Typical gross features included large size (mean diameter 11.3 cm), a mucoid texture, foci of necrosis, and prominent cyst formation. Nine major histologic patterns were identified (classic, myxoid, sclerosing, cellular, epithelioid, palisading, spindle, storiform, and anaplastic); virtually all tumors contained multiple patterns that blended with one another. Immunohistochemical stains were performed on 45 cases; only vimentin was consistently immunoreactive. Consistently negative results with other antibodies helped exclude other tumors in the differential diagnosis; all CCSKs were cytokeratin-negative, including epithelioid tumors that mimicked Wilms tumor, and MIC2-negative, including cellular tumors that mimicked primitive neuroectodermal tumor. The p53 gene product was rarely overexpressed in non-anaplastic CCSKs, but strikingly overexpressed in two of three anaplastic CCSKs. Overall survival was 69%. Multivariate analysis revealed four independent prognostic factors for survival: treatment with doxorubicin, stage, age at diagnosis, and tumor necrosis. Of note, stage 1 patients had a remarkable 98% survival rate. No other histologic or clinical variable independently correlated with survival.
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PMID:Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. 1063 83

The aim of this study was to describe a child with a right cerebellar hemisphere metastasis from primary clear cell sarcoma of the kidney without evidence of bone metastases, and to investigate the immunohistochemical features of primary and metastatic tumors. A 12-month old boy was admitted our hospital due to an abdominal mass. Abdominal computed tomography revealed a large right renal tumor. Tumor was removed with nephrectomy. Histopathologic examination of tumor revealed clear cell sarcoma of the kidney. The patient received radiotherapy and chemotherapy in postoperative period. He suffered from gait disturbance and confusion 8 months later. A computed tomography scan revealed a tumor that was enhanced with contrast medium at right cerebellar hemisphere concomitant with ventricular enlargement. After ventriculo-peritoneal shunting procedure, tumor was excised totally and histopathologic diagnosis showed metastasis of clear cell sarcoma of the kidney. Immunohistochemically vimentin, actin, desmin, neuron specific enolase, cytokeratin, P 53, Ki-67 and P-170 were performed using formalin fixed, paraffin embedded sections. Both of the tumors were positive for vimentin and negative for desmin, actin, neuron specific enolase, cytokeratin and P 53. Scattered nuclei were stained by Ki-67 in primary and metastatic cerebellar tumor. Both primary and metastatic tumors were negative for p53 and P-170. The treatment consisted of surgery, radiotherapy and chemotherapy. The patient is alive and well without evidence of recurrence 16 months after second surgery. Clear cell sarcoma of the kidney is most commonly associated with bone metastasis. Cerebellar metastasis of clear cell sarcoma of the kidney is very unusual. To the best of our knowledge, this patient is second case in the English literature. With review of the literature, our immunohistochemical findings support the theory that relapse and metastasis of primary clear cell sarcoma of the kidney are not related with increase of aggressiveness.
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PMID:Cerebellar metastasis from clear cell sarcoma of the kidney. A case report with immunohistochemistry. 1191 76

Mutation of p53 has been implicated in progression of classical Wilms tumor (WT) into the anaplastic variant (AWT), drug resistance, and poor prognosis. Because of prognostic similarities, clear cell sarcoma of the kidney (CCSK) has been classified with AWT and other aggressive pediatric renal tumors, apart from congenital mesoblastic nephroma (CMN), which is instead a relatively benign tumor of neonates. Initially, CCSK and CMN were assumed to be ontologically related, but the role of p53 in the pathogenesis of either disease has not been sufficiently evaluated as in AWT. We examined the status of p53 in CMN and CCSK in comparison to AWT by immunohistochemistry and mRNA analysis of p53, the downstream effector p21(WAF-1/CIP-1) ( p21), the multidrug resistance gene MDR-1, a putative target of p53, and the p53-antagonist Mdm-2. Surprisingly, strong p53 nuclear immunoreactivity was found in cultures from two CMN specimens, but not in frozen or fixed tumor tissue from five other CMN specimens, nor in cell lines or tumor tissue from CCSK. Sequence analysis excluded p53 mutations. The size of the p53 mRNA in CMN and CCSK primary tumors excluded gross deletions or rearrangements. Low levels of Mdm-2 mRNA in CCSK and CMN primary tumors and cultures did not support a role for Mdm-2. Absence of MDR-1 mRNA excluded MDR-1 in the drug-resistant phenotype of CCSK. Cisplatin-induced p21 transactivation assays and G(1) cell cycle arrest analyses showed that p21 transactivation and G(1) arrest occurred in both CCSK and CMN cultures, demonstrating integrity of the p53 signal transduction pathway. Absence of p53 functional abnormalities excluded relationships between CCSK and CMN as in AWT, supporting the association of cellular CMN with congenital fibrosarcomas as more recently proposed.
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PMID:Functional and gene expression analysis of the p53 signaling pathway in clear cell sarcoma of the kidney and congenital mesoblastic nephroma. 1200 18

A high prevalence of p53 gene mutation and protein expression has been found in the anaplastic variant of Wilms' tumor (WT), known to be associated with poor outcome. However, there are very few studies of p53 alterations in the other two rare and highly malignant renal tumors in childhood, in other words, clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumor of the kidney (MRTK). Overexpression of p53 protein has been detected in eight CCSKs in one study, and in two in another, yet no molecular correlation with p53 gene mutations has been carried out. Our study is the first molecular analysis concerning p53 in CCSK. We investigated eight cases of CCSK and one case of MRTK for p53 protein expression by immunohistochemical staining. All were analyzed for p53 mutations in the region of exons 4 to 8 by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) method and DNA sequencing analysis. By histological study, no CCSK showed anaplastic features. None expressed p53 protein, but two harbored p53 mutations. One was in exon 5, with a base pair insertion between codons 162 to 163 causing frameshift alteration in amino acid. Another was a silent CTC-->CTT transversion in codon 289 of exon 8. The case of MRTK did not show any alterations of p53 protein or gene. Our result indicates that p53 alterations are infrequent in CCSK and do not seem to be primary genetic events in the pathogenesis of CCSK.
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PMID:Infrequent p53 gene mutations and lack of p53 protein expression in clear cell sarcoma of the kidney: immunohistochemical study and mutation analysis of p53 in renal tumors of unfavorable prognosis. 1206 73

Clear cell sarcoma (CCSK) of the kidney is an uncommon but distinctive pediatric renal tumor with a characteristic histological pattern and marked propensity for bone metastasis. The rare anaplastic variant constitutes about 3% of cases of CCSK and carries an unfavorable prognosis, with increased tumor recurrence and resistant to chemotherapy. This variant show high frequency of p53 gene mutation and p53 over expression in comparison to the usual CCSK. We present a case of anaplastic variant of CCSK in an 10-year-old boy with both cytologic and histologic features, highlighting the importance of recognizing this rare entity.
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PMID:Anaplastic variant of clear cell sarcoma of the kidney: a rare case report. 2060 42