Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P52742 (pT3)
 1,034 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many morphologic parameters have been used in prognostic studies in renal cell carcinoma. In this study, the relationship between these parameters and prognosis was investigated. This study includes 75 patients who were treated with radical nephrectomy between 1985 and 2001. Pathological stage (TNM), grade (Fuhrman nuclear grade) cell type (UICC and AJCC), histologic pattern, tumour size, vascular invasion and multifocality were used as prognostic parameters. There were 34 female and 41 male patients with mean age of 54.5 +/- 12.5. The mean size of the tumour was 76.9 +/- 37.2 (30-200) mm. Of the patients, 40 had pT1, 21 pT2, nine pT3 and two pT4 diseases. Twenty-eight patients had Grade 1, 29 Grade 2, 15 Grade 3 and three Grade 4 tumour. According to cell type, 63 had clear cell, six papillary and six undifferentiated types. Five had multifocal and seven had vascular invasion. In conclusion, nuclear grade and tumour stage were found as the most important prognostic indicators.
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PMID:Prognostic significance of morphologic parameters in renal cell carcinoma. 1516 Nov 15

Dysregulation of apoptosis plays an important role in tumour progression and resistance to chemotherapy. The X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known inhibitor of apoptosis-family members. Only recently, an antagonist of XIAP has been identified, termed Smac/DIABLO. To explore the relevance of antiapoptotic XIAP and proapoptotic Smac/DIABLO for tumour progression in renal cell carcinomas (RCCs), we analysed XIAP and Smac/DIABLO mRNA and protein expression in the primary tumour tissue from 66 RCCs of all major histological types by quantitative real-time PCR, Western blot and ELISA. X-linked inhibitor of apoptosis and Smac/DIABLO mRNA expression was found in all RCCs. Importantly, the relative XIAP mRNA expression levels significantly increased from early (pT1) to advanced (pT3) tumour stages (P=0.0002) and also with tumour dedifferentiation (P=0.04). Western blot analysis confirmed the tumour stage-dependent increase of XIAP expression on the protein level. In contrast, mRNA and protein expression levels of Smac/DIABLO did not significantly change between early and advanced tumour stages or between low and high tumour grades. Consequently, the mRNA expression ratio between antiapoptotic XIAP and proapoptotic Smac/DIABLO markedly increased during progression from early (pT1) to advanced (pT3) tumour stages. Moreover, RCCs confined within the organ capsule (pT1 and pT2) exhibited a significantly lower XIAP to Smac/DIABLO expression ratio when compared with RCCs infiltrating beyond the kidney (pT3; P=0.01). Thus, our investigation demonstrates that the delicate balance between XIAP and Smac/DIABLO expression is gradually disturbed during progression of RCCs, resulting in a relative increase of antiapoptotic XIAP over proapoptotic Smac/DIABLO, thereby probably contributing to the marked apoptosis resistance of RCC.
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PMID:Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas. 1532 23

p27 (p27/kip1) is involved in cell-cycle control, and loss of p27 expression may result in tumour development and/or progression. Association with Skp2 targets p27 for degradation. Using a tissue microarray technique, 171 primary renal cell carcinomas (RCCs) and 58 RCC metastases were immunostained for p27 and Skp2. p27 Immunoreactivity was noted in 83 of 129 (64%) clear cell, 6 of 22 (27%) chromophobe and 15 of 20 (75%) papillary tumours as well as 44 of 58 (76%) metastases. In clear cell cancers, high p27 expression (> or =50% of tumour cells) decreased with rising tumour stage (50% pT1/pT2 versus 20% pT3; P<0.001) and grade (44% G1/G2 versus 21% G3/G4; P=0.008). None of 22 chromophobe cancers showed high expression in contrast to 46 of 129 (36%) clear cell tumours (P<0.001). Skp2 expression was noted in 8 of 129 (6%) clear cell cancers and 11 of 55 (20%) metastases (P=0.008). Immunoreactivity increased with rising tumour stage (1% pT1/pT2 versus 11% pT3; P=0.03) and grade (1% G1/G2 versus 15% G3/G4; P=0.004) and was associated with sarcomatoid morphology (P<0.001). In multivariate analysis, patients with low p27 expression and Skp2 immunoreactivity in clear cell cancers had a less favourable outcome. In conclusion, p27 and Skp2 proved to be additional biomarkers in renal cancer pathology with both prognostic and diagnostic impact.
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PMID:Biological significance of p27 and Skp2 expression in renal cell carcinoma. A systematic analysis of primary and metastatic tumour tissues using a tissue microarray technique. 1551 66

There is an increased incidence of tumors of the genitourinary tract among kidney graft recipients. From 1979 to 2001, all patients who received kidney transplants had records of both their underlying diseases and their initial immunosuppression. Patients who developed a genitourinary tract malignancy were evaluated for tumor type, location, stage, tumor therapy and clinical course. During this period, 1804 patients underwent 2068 kidney transplantations. Thirty-four patients had 39 tumors of genitourinary origin. One patient was lost to follow-up. There were 15 patients with 18 renal cell carcinomas (one of them multifocal): six had seven transitional cell carcinomas; six, prostatic carcinoma; six, tumor of the female genital tract (one also had a renal cell carcinoma); and two, a seminoma. Most tumors were diagnosed in their early stages (< or = pT3, N0, M0; n = 31 tumors) and thus accessible to curative therapy, achieving good long-term results: 1- and 5-year survival rates of 100% and 91%, which were better than those obtained in advanced stages (N+, M+; n = 7 tumors), namely both 1- and 5-year survival rates of 38% (P < .05). Death was caused by tumor growth in nine patients (27%) and by other causes in three patients (9%). With appropriate treatment genitourinary tumors at early stage show a good prognosis. New immunosuppressants with supposed antiproliferative effects may help to decrease the incidence of malignancies. The most important factor is risk-adapted screening to identify malignancies early and to initiate appropriate therapy.
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PMID:Therapy and prognosis of tumors of the genitourinary tract after kidney transplantation. 1596 47

For identification and targeting of tumor-associated marker proteins, the proteome of clear cell type of renal cell carcinoma (RCC) and normal kidney tissues was analyzed by 2-DE. Ketohexokinase (also called fructokinase), which catalyzes the phosphorylation of fructose to fructose 1-phosphate, was identified by MALDI-TOF MS and found to be expressed at low rates in the renal tumor tissues. We found a decreased amount of ketohexokinase mRNA in RCC compared to that observed in the normal kidney tissues by Northern blot. The activity of ketohexokinase in 20 clear cell RCC specimens and the 20 corresponding normal kidneys was investigated, and its activity was shown to be approximately 1.4-fold lower in the RCC specimens than in the normal kidney. Ketohexokinase activity in tumor stage pT3 RCC was 1.5-fold lower than in pT1 RCC. The level of ketohexokinase activity in histological grade 3 RCC was 1.8-fold lower than that in grade 1 cancer. In addition, using in situ hybridization, it was revealed that ketohexokinase in the normal kidney tissue was confined to the proximal tubular epithelial cells, while the expression of ketohexokinase in RCC tissues was extremely low. Our research results show that the expression of human ketohexokinase was diminished in clear cell RCC.
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PMID:The expression of ketohexokinase is diminished in human clear cell type of renal cell carcinoma. 1637 72

Transcriptional downregulation of the putative tumor suppressor gene XIAP-associated Factor 1 (XAF1) by promoter methylation has been shown to relate to tumor progression of gastric and bladder cancer. This study determined the mRNA expression levels and the methylation status of XAF1 by real-time RT-PCR and quantitative methylation specific PCR in tumor tissue obtained from 91 renal cell carcinoma (RCC) patients (median follow-up 50.5 months) following surgical treatment. Expression data was correlated to histopathological variables and outcome. XAF1 expression levels were not related to standard pathological parameters for outcome prediction but results from crude and explorative multivariable-adjusted analyses revealed low XAF1 levels to significantly increase the relative risk (RR) for tumor recurrence (RR 4.6; CI 95%: 1.4-14.6) and tumor-related death (RR 3.6; CI 95%: 1.4-9.7). The association of low XAF1 expression with an abbreviated recurrence-free (p=0.009) and disease-specific survival (p=0.005) was most pronounced in patients with locally advanced (pT3) tumors. XAF1 promoter methylation was rarely detected (10%) but, if present, XAF1 mRNA expression levels correlated inversely to the normalized index of methylation (p=0.01). Our findings suggest that low XAF1 mRNA expression levels relate to an unfavorable clinical course in RCC patients. Promoter methylation may be one, but probably not the essential mechanism for transcriptional downregulation of the XAF1 gene in RCC.
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PMID:Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: correlations with pathology and outcome. 1744 73

The involvement of peptidases in carcinogenetic processes of several tumor types has been researched in recent years. Although kidney is one of the major tissues known to express cystinyl-aminopeptidase (CAP), little is known about its role in renal neoplasia. This study analyzes fluorimetrically membrane-bound and soluble CAP activity in the three main renal cancers: clear cell (CCRCC), papillary (PRCC), and chromophobe (ChRCC) renal cell carcinomas. Overall, a marked decrease of membrane-bound CAP activity in all the three renal cell carcinomas was detected when compared with their respective surrounding non-tumor tissues. So, the tumor vs. non-tumor CAP ratios (units of peptidase per mg of protein) was as follows: 926+/-111 vs. 3778+/-276 for CCRCCs, 737+/-181 vs. 4351+/-950 for PRCCs, and 592+/-118 vs. 4905+/-935 for ChRCCs. In contrast, the soluble fraction of this enzyme displayed minor and non-significant changes when comparing tumor and non-tumor CAP activities in the whole series. After stratification by stage and grade, CCRCCs displayed significant differences: pT3 category had significantly higher levels of membrane-bound activity than pT1, and high grade cases (G3-4) had higher soluble CAP activity than low grade ones (G1-2). These data may open additional possibilities in the study of renal cell carcinoma with regard to the prognosis of patients.
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PMID:Cystinyl aminopeptidase activity is decreased in renal cell carcinomas. 1769 1

A 54-year-old woman consulted our hospital with the complaint of microscopic hematuria and proteinuria. Abdominal computed tomographic scan revealed a tumor mass on the lower pole of the left kidney. Left radical nephrectomy was performed under the diagnosis of renal cell carcinoma. The pathological diagnosis was a collision tumor consisting of renal cell carcinoma (clear cell type, G3, INFalpha, pT1b, v -) and urothelial carcinoma of the renal pelvic (G3 >> G2, pT3, ly + , v +). Postoperative chemotherapy was not given. Convalescence was uneventful and one year after the operation she is alive with no recurrence or metastasis.
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PMID:[A case of synchronous ipsilateral renal cell carcinoma and renal pelvic urothelial carcinoma (collision tumor): a case report]. 1793 38

T3 renal cell carcinoma (RCC) is a heterogeneous group of tumors that are substaged based on perirenal or sinus fat invasion, adrenal invasion, and renal vein invasion. To evaluate whether the extent of fat invasion (minimal versus extensive) and direct adrenal gland invasion, renal vein invasion with or without concurrent fat invasion has a similar prognosis, we retrospectively reviewed 198 T3N0/NxM0 RCCs in a single academic tertiary hospital. Fat invasion was subdivided as minimal (< or =5 mm into the fat) or extensive (>5 mm) invasion. Direct adrenal invasion was defined as contiguous involvement of ipsilateral adrenal gland. Among the 198 T3 RCCs, minimal and extensive fat invasions were identified in 57 and 61 cases, respectively; renal vein invasion and direct adrenal invasion were seen in 66 and 14 cases. The patients' average age was 62.9 years, and 145 patients were male and 53 were females. The 2-year and 5-year survival rates were 85% and 56% for minimal fat invasion, 76% and 70% for extensive fat invasion, and 55% and 32% for renal vein invasion, respectively. There was no difference of survival in patients with T3b (renal vein invasion) RCC stratified by presence or absence of concurrent fat invasion. The 2-year and 5-year survival rates for adrenal invasion were 31% and 21%, respectively, which was significantly worse than that of fat or renal vein invasion. Multivariate analysis showed that nuclear grade, sarcomatoid differentiation, and subgrouping of pT3 RCC (fat invasion, renal vein invasion, and adrenal invasion) remained independent predictors of patient's overall survival. In conclusion, our study shows that T3 RCCs with minimal or extensive perinephric fat invasion has a similar prognosis and is significantly more favorable than that of renal vein invasion regardless of presence or absence of concurrent fat invasion. In contrast, tumors with adrenal gland invasion carry a far worse prognosis than perinephric fat or renal vein invasion and thus supporting a separate stage category.
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PMID:Reappraisal of T3N0/NxM0 renal cell carcinoma: significance of extent of fat invasion, renal vein invasion, and adrenal invasion. 1865 40

A distinctive tumor described under the terms Bellini duct carcinoma and low-grade collecting duct carcinoma has been referred to by us and others as tubulocystic carcinoma. This renal cell carcinoma subtype is not recognized in the World Health Organization 2004 classification. Herein, we present a detailed study of 31 cases to further characterize this rare subtype of renal cell carcinoma. The tumor occurred in adults (mean age, 54 years) with a strong male predominance (7:1). Grossly, the tumors ranged from 0.7 to 17 cm, and exhibited a spongy or "bubble wrap" appearance reflecting the microscopic presence of variably sized cystically dilated tubules lined by a single layer of epithelium. The lining varied with a cuboidal, flat, and hobnail cell appearance, and the neoplastic cells had abundant eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli. The cysts were closely spaced with an intervening variably fibrotic stroma. Immunohistochemistry and ultrastructural examination showed features of proximal convoluted tubules (Pax 2 immunoreactivity and short microvilli with brush border organization) and distal nephron (kidney-specific cadherin immunoreactivity and cytoplasmic interdigitation). Gene expression profiling showed that tubulocystic carcinoma displayed a unique molecular signature. Twenty-four tumors were stage pT1, 4 stage pT2, and 3 stage pT3. Disease progression (median follow-up of 56 months) occurred in 3 patients; 1 with local recurrence, and 2 with distant metastasis to bone and liver. In light of the distinctive clinicopathologic features and a low but definite metastatic potential, this unique subtype of renal cell carcinoma deserves formal recognition in the contemporary classification of renal neoplasms.
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PMID:Tubulocystic carcinoma of the kidney: clinicopathologic analysis of 31 cases of a distinctive rare subtype of renal cell carcinoma. 1901 62


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