Browsing by Subject "Renal cell carcinoma"
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- PublicationOpen AccessExpression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis(Murcia : F. Hernández, 2007) Ramp, U.; Mahotka, C.; Heikaus, S.; Shibata, T.; Grimm, M.O.; Willers, R.; Gabbert, H.E.Heat shock proteins (HSPs) play an important role in the cellular response to environmental stress and exert a cytoprotective effect. Especially HSP70 is an effective inhibitor of apoptosis, suggesting a role of HSP70 in carcinogenesis and tumor progression. To explore the relevance of HSP70 in renal cell carcinomas (RCCs), we analyzed nuclear and cytoplasmic HSP70 protein expression in formalin-fixed tissue from 145 clear cell RCCs by immunohistochemistry as well as Western blot analysis. Nuclear HSP70 expression was found in all RCCs and 75% of the tumors also exhibited a cytoplasmic HSP70 staining. Importantly, RCCs showed significantly reduced cytoplasmic (p=0.001) and combined nuclear/cytoplasmic (p=0.0022) HSP70 expression when compared with their cells of origin. A significant (p=0.0176) decrease of nuclear HSP70 expression became evident from well to poorly differentiated clear cell RCCs. Quite similarly, a trend (p=0.0558) for reduced combined nuclear/cytoplasmic HSP70 expression was shown from early (pT1) to advanced (pT3) tumor stages. Nevertheless, no correlation between HSP70 expression and patients´ survival became evident. In conclusion, our investigation demonstrates a significant decrease of antiapoptotic HSP70 protein expression during carcinogenesis and during progression from well (G1) to poorly (G3) differentiated clear cell RCCs. Our results suggest that HSP70-mediated inhibition of apoptosis seems to be of minor importance for carcinogenesis and tumor progression in RCCs.
- PublicationOpen AccessIncreased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma(Murcia : F. Hernández, 2007) Faronato, M.; Muzzonigro, G.; Milanese, G.; Menna, C.; Bonfigli, A.R.; Catalano, A.; Procopio, A.The clinical behaviour of Clear Cell Renal Cell Carcinoma (CC-RCC) is often unpredictable. To fully understand the signaling pathways involved in CCRCC development, we examined whether the 5- Lipoxygenase (5-LO), which catalyzes the biosynthesis of proinflammatory leukotrienes, is involved in renal tumorigenesis. By analyzing 46 snap-frozen primary renal cell carcinomas and their corresponding normal renal cortex biopsies, 5-LO protein levels were found to be significantly increased in the majority of CC-RCCs (P<0.001). Quantitative 5-LO mRNA expression analysis revealed up to 3-fold increased expression in the tumor tissues. There was no association between 5-LO and gender, grade or vein invasion. In contrast, increased 5-LO protein and mRNA correlated with large tumor size (>4 cm) and age of patients (P<0.001). 5-LO was frequently overexpressed in von Hippel-Lindau protein (pVHL)–reduced tumors and in Vascular Endothelial Growth Factor (VEGF)-positive tumors, which represent two frequent alterations in CC-RCC. Cell culture experiments demonstrated that VEGF expression was strongly inducible by 5-LO metabolites in RCC cell lines. The loss of pVHL expression led to high basal 5- LO and VEGF expression, which were markedly reduced by transfection with 5-LO small interfering RNA (siRNA). These results suggest that 5-LO upregulation is an important step in renal cancer progression.
- PublicationOpen AccessIncreasing expression of fascin in renal cell carcinoma associated with clinicopathological parameters of aggressiveness(Murcia : F. Hernández, 2006) Jin, J.S.; Yu, C.P.; Sun, G.H.; Lin, Y.F.; Chiang, H.; Chao, T.K.; Tsai, W.C.; Sheu, L.F.Aim: To determine whether higher expression of fascin, an actin-bundling protein associated with motility, in conventional renal cell carcinoma (RCC) is associated with more advanced stages of the disease. Methods: Immunohistochemical analysis of fascin expression was performed in tissue microarrays of 108 RCCs including 55 clear cell RCCs (CRCCs), 39 CRCCs with granular cell differentiation (GRCCs), 8 CRCCs with sarcomatoid differentiation (SRCCs) and 6 metastatic RCCs. Results: The expression of fascin was undetectable in normal renal tubules of all control cases. However, among the 108 RCC cases, fascin immunoreactivity was seen on the cell membrane and cytoplasm. The average immunostaining score for fascin was 128/400 in grade I, 170/400 in grade II, 207/400 in grade III, and 323/400 in grade IV RCC. The average immunostaining score of fascin was 187/400 for stage T1, 205/400 for stage T2, 288/400 for stage T3, and 355/400 for stage T4 cases of RCCs. Higher fascin scores in RCC were significantly correlated with higher T and N stages and nuclear grade. In addition, the fascin scores in GRCC (368±19) and SRCC (263±21) were significantly higher than in CRCC 95±18). Conclusions: Our findings demonstrate for the first time that increased expression of fascin is associated with clinicopathological parameters of aggressiveness in patients with RCC. Fascin may be a novel biomarker for diagnosis and treatment of RCC.
- PublicationOpen AccessMiT family translocation renal cell carcinomas: A 15th anniversary update.(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Gandhi, atin S.; Malik, Faizan; Amin, Mahul B.; Argani, Pedram; Bahrami, ArmitaMicrophthalmia (MiT) family translocation renal cell carcinomas (RCCs) are a heterogeneous category of renal tumors which all express MiT transcription factors, typically from chromosomal translocation and rarely from gene amplification. This tumor family has two major subtypes [i.e., Xp11 translocation RCC and t(6;11) RCC] and several related neoplasms (i.e., TFEB amplification RCC and melanotic Xp11 translocation renal cancers). Increased understanding of the clinical, pathological, molecular and prognostic heterogeneity of these tumors, since their official recognition in 2004, provides the opportunity to identify prognostic biomarkers and to understand the reasons for tumor aggression. We will review the literature from the past 15 years and highlight the need for a greater understanding of the molecular mechanisms underpinning heterogeneous tumor behavior
- PublicationOpen AccessMucinous tubular and spindle cell carcinoma with Fuhrman nuclear grade 3, A histological, immunohistochemical, ultrastructural and FISH study(Murcia : F. Hernández, 2008) Kuroda, Naoto; Hes, O.; Michal, Michal; Nemcova, J.; Gal, V.; Yamaguchi, T.; Kawada, T.; Imamura, Y.; Hayashi, Yoshihiro; Lee, Gang-HongMucinous tubular and spindle cell carcinoma (MTSCC) of the kidney generally shows low nuclear grade. MTSCC with high nuclear grade is relatively rare. In this article, we report two cases of MTSCC with Fuhrman grade 3. One case occurred in a 57-year-old Japanese female and the second case in a 49-year-old Caucasian female. Histologically, the tumors were composed of neoplastic cells with cuboidal or columnar and spindle morphology, and Fuhrman nuclear grade 3. The myxoid stroma was also observed. This stroma was positive for Alcian blue stain. Immunohistochemically, neoplastic cells of both cases were positive for AMACR, but negative for CD10 and RCC Ma. Ultrastructurally, tumorous cells of one case contained numerous mitochondria. In FISH analysis, many neoplastic cells of both cases demonstrated monosomy of chromosomes 15 and 22 and disomy of chromosomes 7 and 17. One of the two patients died of respiratory failure due to pleuritis carcinomatosa 48 months postoperatively. Finally, the pathologist should recognize that high grade MTSCC exists despite its rare frequency. FISH analysis may be helpful in establishing the diagnosis of this entity. Furthermore, we present the first report of a patient with MTSCC dying of distant metastasis.
- PublicationOpen AccessProtein expression and gene mutation status of KIT and PDGFRA in renal cell carcinoma(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Terada, TadashiThe author investigated protein expression and gene mutations of KIT and PDGFRA in 61 consecutive surgical cases of renal cell carcinoma (RCC). The cases of RCC consisted of 43 clear cell RCC (CCRCC), 9 chromophobe RCC (ChrRCC), or 9 papillary RCC (PaRCC). Normal distribution of KIT and PDGFRA protein was also examined in non-tumorous normal parenchyma (n=10). In normal kidneys, KIT was expressed in distal convoluted tubules and collecting ducts, and PDGFRA in distal and proximal convoluted tubules and collecting ducts. KIT expression was recognized in 9 ChrRCC (100%, 9/9), but not in 43 CCRCC (0%, 0/43) and 9 PaRCC (0%, 0/9). PDGFRA expression was recognized in 7 CCRCC (16%, 7/43) and 2 PaRCC (28%, 2/9), but not in ChrRCC (0%, 0/9). A molecular genetic analysis using PCR-direct sequencing was performed in selected 30 cases (ChrRCC=9, CCRCC=12, PaRCC=9): it revealed no mutations in KIT (exons 9, 11, 13, and 17) or PDGFRA (exons 12 and 18) genes in any cases examined. These results suggest that in normal renal parenchyma KIT is expressed in distal convoluted tubules and collecting ducts, and PDGFRA in proximal and distal convoluted tubules and collecting ducts, that KIT is expressed exclusively in ChrRCC and its incidence is 100%, that KIT-positive ChrRCC was negative for PDGFRA, that PDGFRA is expressed in a small percentage in CCRCC and PaRCC, and that mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) are absent in RCC.
- PublicationOpen AccessRetrospective analysis of 25 immunohistochemical tissue markers for differentiating multilocular cystic renal neoplasm of low malignant potential and multicystic renal cell carcinoma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Kim, Sung Han; Park, Boram; Joo, Jungnam; Joung, Jae Young; Seo, Ho Kyung; Lee, Kang Hyun; Park, Weon Seo; Chung, JinsooMultilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and multicystic renal cell carcinoma (MCRCC) are morphologically indistinguishable. MCRNLMP is a tumor composed entirely of numerous cysts, the septa of which contain individual or groups of clear cells without expansile growth. However, unlike MCRCC, neither recurrence nor metastasis has been reported in MCRNLMP. The aim of this study was to identify significant differential pathological characteristics in resected specimens from patients diagnosed with MCRNLMP (n=13) and MCRCC (n=17) using immunohistochemistry of 25 tissue markers. Staining interpretation was performed semi-quantitatively using the H-score (0-300) or intensity score (0-3), and differences between groups were evaluated using the Fisher exact and Wilcoxon rank-sum tests. During a median follow-up of 66.2 months (1-141.9 months), there was only one case of MCRCC recurrence among all 30 patients, including 19 (63.3%) at stage pT1a, 8 (26.7%) at stage pT1b, and 3 (10.0%) patients at stage pT2. Tumor necrosis rate (0% vs. 52.9%) and median tumor size (3.2 cm vs. 4.1 cm) significantly differed between MCRNLMP and MCRCC samples. Among the 25 tissue markers, only HIF1a, PDGFRα, SMA, VEGFR1, VEGFR2, VEGFR3, CD10, CD31, CD34, CK7-tubule, TGAse-2, and Ki-67 showed significantly different expression between the groups. These tissue markers with differential expression between MCRNLMP and MCRCC can provide a clue to understanding their distinct pathophysiology.
- PublicationOpen AccessSarcomatoid acquired cystic disease-associated renal cell carcinoma(Murcia : F. Hernández, 2008) Kuroda, Naoto; Tamura, Masato; Taguchi, Takahiro; Tominaga, Akira; Hes, Ondrej; Michal, Michal; Ohara, Masahiko; Hirouchi, Takashi; Mizuno, Keiko; Hayashi, Yoshihiro; Shuin, Taro; Lee, Gang-HongIn this article, we report a rare case of hitherto undescribed acquired cystic disease (ACD)- associated renal cell carcinoma (RCC) with sarcomatoid change. A 78-year-old woman had been receiving hemodialysis for fourteen years at the time when a renal tumor was encountered on the follow-up examination of the kidney. Microscopically, oncocytic cuboidal cells proliferated with tubular, cribriform or papillary growth patterns, and atypical columnar cells with abundant cytoplasm proliferated with papillary configuration. Oxalate crystal deposition was observed in the stroma and the tumor focally resembled translocation type (TFE3) RCC. Sarcomatous neoplastic cells were also seen. The cytoplasm of oncocytic and sarcomatous neoplastic cells was diffusely positive for antimitochondrial antibody and the ultrastructural examination detected many mitochondria in the cytoplasm of oncocytic carcinoma cells and sarcomatous neoplastic cells. The loss of chromosomes 1p, 2q11-22, 9 and 14 was observed using comparative genomic hybridization analysis. We thus report here a case of hitherto undescribed ACD-associated RCC intermingled with oncocytic cells, translocation type RCC-like area and sarcomatoid change. This is the sixth case of sarcomatoid RCC arising in end-stage kidney disease.
- PublicationOpen AccessSelective nuclear morphometry as a prognostic factor of survival in renal cell carcinoma(Murcia : F. Hernández, 1999) Monge, J.M.; Val-Bernal, José Fernando; Buelta, L.; Garcia-Castrillo Riesgo, L.; Asensio, L.In the present study, we sought to determine the predictive value of selective nuclear morphometry (SNM) for patient outcome in renal cell carcinoma (RCC). Tumor samples of 140 renal adenocarcinomas diagnosed and treated with radical nephrectomy and hilar lymphadenectomy between 1970 and 1988 with a minimum follow up of 5 years in all the cases were studied by SNM. The morphometric analysis was performed in the most malignant tumor selected zone. Selection was based on cytological criteria including nuclear grade. Nuclear morphometric features analyzed were: area, perimeter, major diameter, major and minor diameter of the equivalent ellipse, volume of the equivalent ellipse and sphere, circumference diameter, and shape factors. The results showed that in the selected zone tumor nuclei were larger than in the zones selected at random. There was an inverse correlation between morphometric parameters and survival and a direct one between tumoral grade and stage. Tumors of the longterm survival group of patients presented nuclei with smaller morphometric measurements than tumors of short term survival group, with significant differences between them (pe0.05). In the survival analysis carried out by the Kaplan-Meier method significant differences existed between different groups formed from break point for: area, perimeter, major diameter, major and minor diameter of the ellipse, volume of the ellipse and sphere, circumference diameter and perimeter shape factor. In the multivariate analysis carried out by the Cox method, the feature with the most predictable value related to survival, was the tumor stage. Morphometric value with the highest punctuation in the test was major nuclear diameter. The rest of the morphometric values (except elliptic shape factor and elongation factor) were also significant but they did not improve prognostic information of the major nuclear diameter. SNM offers a useful aid in a more objective grading of RCC. Multivariate Cox analysis revealed additional value of karyometry to tumor stage. SNM can be a useful tool for stratification of patients with RCC.