Conventional Renal Cell Carcinoma Research Articles

Tumor-to-tumor metastasis: Case report of a pulmonary adenocarcinoma metastatic to a clear cell renal cell carcinoma

Tumor-to-tumor metastasis is a very rare event. The recipient tumor may be benign or malignant. Renal cell carcinoma is the most common tumor recipient of metastasis while lung carcinoma is the most common donor tumor. We report a 57-year-old Caucasian male who presented with chest pain. On PET CT Scan, he was also found to have a large renal mass for which he underwent left nephrectomy. On histology of the renal mass, the tumor was a conventional renal cell carcinoma with areas of metastatic non-small cell lung carcinoma. The two components had a distinctive morphology which was confirmed on subsequent immunohistochemistry. The physiopathological mechanisms making clear cell renal cell carcinoma an avid recipient of a metastatic carcinoma have been speculated upon, but are still unknown.

Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition

Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma.

Investigation of tumor suppressor genes apart from VHL on 3p by deletion mapping in sporadic clear cell renal cell carcinoma (cRCC)

ObjectivesTo investigate the most recurrent deletion loci on 3p12-p26 by deletion mapping studies by PCR-LOH and BAC array-FISH in sporadic conventional renal cell carcinoma (cRCC) and further, to evaluate the their clinicopathologic significance in cRCC. Comparative allelotyping studies in cRCC and major epithelial carcinomas (MEC) such as lung, breast, and bladder tumors were also carried out to investigate the specificity of the targeted loci in cRCC. Subjects and methodsA total of 40 c-RCC patients were enrolled in this study, categorized in to 2 groups: group I comprises of patients of stages I and II and group II includes patients at stages III and IV. Loss of heterozygosity (LOH) studies were performed by PCR using 15 microsatellite markers of region 3p12-p26 on paired normal-tumor tissues. The recurrent LOH loci found in 27 cRCC tumors were further validated by BAC array-FISH using 23 serially mapped BAC clones. Simultaneously, the allelic deletion status of fragile histidine triad (FHIT) gene was studied by FISH in cRCC and major epithelial carcinoma (MEC) tumors. The numerical aberrations of chromosome 3 were also studied using the centromere enumeration probe (CEP) probe for chromosome 3 to validate the observed allelic losses by BAC array-FISH in cRCC as well as MECs. ResultsOur study revealed 3 affected regions of LOH on 3p in cRCC: 3p12.2-p14.1, 3p14.2-p21.1, and 3p24.2-p26.1 in both group I (stages I and II) and group II (stage III and IV). Comparative allelotyping studies revealed that except for LOH loci D3S2406 (20%), D3S1766 (14%), and D3S1560 (20%), remaining affected loci revealed retention of heterozygosity (ROH) in breast carcinomas. Lung and bladder tumors revealed ROH at all affected LOH loci. FISH with FHIT gene probe revealed deletions in cRCC (88%), breast (30%), and lung tumors (10%). FHIT gene deletions frequency was almost equal in both groups I and II (>70%), whereas a locus 3p13 (D3S2454) revealed the highest LOH in group II (83%) patients in comparison to group I (16%). BAC array-FISH studies in cRCC identified 15 recurrent deletion loci at crucial regions, 3p12.2, 3p14.2, 3p21.3, and 3p24.2-p26 with long continuous deletion of 3p14.1-p26.1 exclusively in patients of stages III and IV. Validation of LOH loci in breast carcinomas by BAC array-FISH with BAC clones mapped at these loci revealed comparatively lower deletion frequency for RP11-59E22 (3p12.2) (30%), RP11-759B7(3p21.1) (12%), and RP11-57D6 (3p25.2, proximal to VHL) (15%) than cRCC. ConclusionMolecular cytogenetic studies by BAC array-FISH was found to be more sensitive over LOH. Deletion patterns on 3p explored that deletion of FHIT and flanking loci may occur as an initiating event followed by deletions at 3p12.2, 3p21.31–3p21.32, and 3p24.2–3p26.1 in the initial stage of development of disease, while continuous large deletions of 3p21.3–3p26.1 and 3p14.1–3p26.1 occur as progressive deletion due to genetic instability. Lack of VHL along with flanking loci in 50% cRCC patients that included both groups I and II supported the hypothesis of both VHL dependent and VHL independent pathways in cRCC tumorigenesis. Comparative allelotyping studies in cRCC and MECs indicated association of specific targeted loci including VHL in cRCC. Further expansion of these studies with characterization of the genes at targeted loci and correlation with clinical outcome will explore the prognostic significance and also provide an insight into the mechanisms of tumor suppressive pathways in genitourinary cancers such as CRCC.

Renal-Cell Carcinomas in End-Stage Kidneys

Clear-cell papillary renal-cell carcinoma (CCPC) and acquired cystic kidney disease-associated carcinoma (ACDAC) are neoplasms with distinct morphological characteristics that behave less aggressively than conventional renal-cell carcinomas. End-stage kidney specimens from 61 patients (47 males and 14 females) with 109 renal-cell carcinomas were selected. Papillary renal-cell carcinoma was the most common malignancy (61/109, 56%), followed by CCPC (20/109, 18%). The CCPC showed a papillary or tubular/solid architecture, clear cytoplasm, low nuclear grade, and a distinct immunohistochemical profile (RCC-, vimentin+, CK7+, p504S-). ACDAC displayed a variety of architectural patterns, eosinophilic cytoplasm, high nuclear grade, intratumoral calcium oxalate deposits, and an immunohistochemical profile similar to type 2 papillary renal-cell carcinoma (RCC+, vimentin+, CK7-/+, p504S+). Less than 5% (3/69) of pathologically staged renal-cell carcinomas in end-stage kidneys presented with lymphogenous and/or hematogenous metastases.

Alterations of ubiquitylation and sumoylation in conventional renal cell carcinomas after the Chernobyl accident: a comparison with Spanish cases

We determined whether ubiquitylation and sumoylation processes are involved in conventional renal cell carcinogenesis associated with chronic, long-term, persistent low doses of ionizing radiation (IR) in patients living for more than 20years in cesium-137 ((137)Cs)-contaminated areas after the Chernobyl accident in Ukraine. To this end, we assessed the immunohistochemical expression of ubiquitin (Ub), SUMO1, SUMO E2 conjugating enzyme Ubc9, and the cell cycle regulators p53, mdm2, and p14(ARF) in 38 conventional renal cell carcinomas from Ukrainian patients with different degrees of radiation exposure after the Chernobyl accident. As control cases, 18 conventional renal carcinoma (cRCC) tissues from a Spanish cohort were analyzed. No significant differences between the Ukrainian and Spanish groups were found regarding Ub overexpression, although being higher in the Ukrainian cases. Furthermore, this expression was inversely associated with SUMO1 and Ubc9, with no correlation with tumor nuclear grade. There was also a direct relationship between Ubc9 and inflammatory response. These findings do not allow us to consider the immunohistochemical expression of ubiquitylation and sumoylation as valuable markers for discriminating the effects of long-term, low-dose IR exposure in cRCC carcinogenesis.

Pathologic Significance and Prognostic Value of Phosphorylated Cortactin Expression in Patients With Sarcomatoid Renal Cell Carcinoma

To clarify the clinical and prognostic significance of cortactin and phosphorylated cortactin in patients with sarcomatoid renal cell carcinoma (SRCC). We retrospectively reviewed the data from 31 patients with SRCC and 33 with conventional renal cell carcinoma matched for clinicopathologic features. The immunoreactive score for cortactin, pY421 cortactin, and pY466 cortactin were measured using immunohistochemistry. The relationships between each immunoreactive score and the clinicopathologic features and survival were investigated. The immunoreactive score of p421 cortactin, but not that of cortactin and pY466 cortactin, was significantly greater in SRCC than in conventional renal cell carcinoma (P < .001). The expression of pY421 cortactin in SRCC correlated with the pT stage and metastasis (P < .001). The expression of pY466 cortactin showed a similar trend with pT stage (P = .043) but not with metastasis. Although both of pY421 cortactin and pY466 cortactin were identified as useful predictors for survival in univariate analyses, only pY421 cortactin expression was considered an independent predictor in patients with SRCC (odds ratio 4.53, 95% confidence interval 1.07-19.12, P = .040) in the multivariate analysis model, including pT stage and metastasis. Our results have demonstrated that phosphorylation of cortactin is a key process in malignant aggressiveness, and its expression is a useful predictor of cause-specific survival and could be a useful potential therapeutic target in patients with SRCC.

The impact of rhabdoid or sarcomatoid differentiation on kidney cancer outcome.

e15188 Background: Clear-cell renal cell carcinoma (RCC) with rhabdoid or sarcomatoid features are rare clinical entities. The current retrospective study sought to define the impact of these pathological features on outcome for RCC. Methods: In reviewing a consecutive series of 458 RCCs who were treated at a single institution between 1997 and 2008, 15 patients of Clear-cell renal cell carcinoma with rhabdoid features (RDRCC) and 35 patients with sarcomatoid change (SRRCC) were identified. Demographic and clinical features, treatment, and survival were compared between RDRCC, RSRCC and those without these features. Differences in cancer specific survival were compared with univariate and multivariate Cox regression analysis. Results: RDRCC and SRRCC were more common in younger than in older patients (p <0.001); more commonly presented with high grade histology (p <0.001) and advanced stage disease (p <0.001). The 3-year cancer specific survival rate was 27.0 %, 25.0% and 73.2% for RDRCC, SRRCC and conventional RCC, respectively. On multivariate analysis there was an increased mortality risk in patients with SRRCC vs RCC (HR 3.69, 95% CI 2.40-5.68, p <0.001); RDRCC vs RCC (HR 4.35, 95% CI 2.22-8.55, p <0.001); Other significant predictor of survival including age at diagnosis (HR 1.03, 95% CI 1.02-1.04, p <0.001); Fuhrman's nuclear grade (HR 1.58, 95% CI 1.07-2.34, p <0.001); tumor stage (HR 2.57, 95% CI 1.78-3.7, p <0.001); and receipt of nephrectomy (HR 0.42, 95% CI 0.30-0.58, p <0.001). Conclusions: Even after adjusting for demographic, pathological and treatment factors, cancer specific survival is significantly worse in patients with SRRCC and RDRCC than conventional RCC.

MicroRNAs as prognostic markers for survival in renal cell carcinoma conventional type T 2-4.

e21115 Background: Renal cell carcinoma (RCC) accounts for more than 3% of adult malignancies and causes more than 13,000 deaths per year in the US alone. Conventional type RCC (CRCC) accounts for ...

965 IMPACT OF INCREASED EXPRESSION OF GLUCOSE-REGULATED PROTEIN 78 ON CLINICOPATHOLOGICAL PARAMETERS AND PROGNOSIS IN RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Evaluation and Staging1 Apr 2011965 IMPACT OF INCREASED EXPRESSION OF GLUCOSE-REGULATED PROTEIN 78 ON CLINICOPATHOLOGICAL PARAMETERS AND PROGNOSIS IN RENAL CELL CARCINOMA Kenji Kuroda, Akio Horiguchi, Takako Asano, Shinsuke Tasaki, Junichi Asakuma, Hidehiko Yoshii, Akinori Sato, Keiichi Ito, Kenji Seguchi, Makoto Sumitomo, and Tomohiko Asano Kenji KurodaKenji Kuroda Tokorozawa, Saitama, Japan More articles by this author , Akio HoriguchiAkio Horiguchi Tokorozawa, Saitama, Japan More articles by this author , Takako AsanoTakako Asano Tokorozawa, Saitama, Japan More articles by this author , Shinsuke TasakiShinsuke Tasaki Tokorozawa, Saitama, Japan More articles by this author , Junichi AsakumaJunichi Asakuma Tokorozawa, Saitama, Japan More articles by this author , Hidehiko YoshiiHidehiko Yoshii Tokorozawa, Saitama, Japan More articles by this author , Akinori SatoAkinori Sato Tokorozawa, Saitama, Japan More articles by this author , Keiichi ItoKeiichi Ito Tokorozawa, Saitama, Japan More articles by this author , Kenji SeguchiKenji Seguchi Tokorozawa, Saitama, Japan More articles by this author , Makoto SumitomoMakoto Sumitomo Tokorozawa, Saitama, Japan More articles by this author , and Tomohiko AsanoTomohiko Asano Tokorozawa, Saitama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.933AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Glucose-regulated protein 78 (GRP78) acts as a chaperone for newly formed proteins during folding and glycosylation. The regulation and expression of GRP78 are associated with resistance to apoptosis in some forms of cancer, but the impact of GRP78 expression on the progression of renal cell carcinoma (RCC) is unclear. To better understand the effects of GRP78 on tumor progression and prognosis in RCC, we assessed its expression by using primary and metastatic tumor sections from patients with RCC and then correlated our findings with clinicopathological parameters, including the patients' survival. METHODS Immunohistochemistry was performed using formalin-fixed and paraffin-embedded specimens, all from the same 128 patients: 128 primary RCC specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. The determination of positive or negative staining was based on the intensity of staining and the percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters, including the patients' survival, was evaluated. RESULTS GRP78 positivity was found in 71 of 128 (55.5%) of the primary tumors and in 8 of 9 (88.9%) specimens taken from the 9 patients with metastasis. GRP78 positivity was also found in most (7 of 8, 87.5%) of the specimens of non-conventional RCC subtypes. Statistically significant associations were found between GRP78 positivity and higher tumor grade (G3; P < 0.0001), advanced T stage (≥ pT3; P = 0.0002), pathological vascular invasion (pV1; P < 0.0001), regional nodal involvement (≥ N1; P = 0.0086), and distant metastasis at presentation (M1; P = 0.001). Positivity for GRP78 was significantly associated with shortened disease-specific survival not only in the patients with conventional RCC (P = 0.0043) but also in all the patients (P = 0.0036). Progression-free survival was also shorter in the patients with positive GRP78 than in those with negative GRP78 (P = 0.0302 for the 106 N0M0 patients with tumors of any cancer cell type, and P = 0.0165 for the 101 N0M0 patients with conventional RCC). CONCLUSIONS Our study showed that a high level of GRP78 expression might be a useful parameter for identifying poor disease-specific and progression-free survival in RCC patients. GRP78 positivity might also contribute to metastatic progression of RCC and could also be used as a marker of aggressiveness for non-conventional RCC subtypes. The findings from the present study could be helpful in the diagnostic and prognostic assessment of RCC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e389 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kenji Kuroda Tokorozawa, Saitama, Japan More articles by this author Akio Horiguchi Tokorozawa, Saitama, Japan More articles by this author Takako Asano Tokorozawa, Saitama, Japan More articles by this author Shinsuke Tasaki Tokorozawa, Saitama, Japan More articles by this author Junichi Asakuma Tokorozawa, Saitama, Japan More articles by this author Hidehiko Yoshii Tokorozawa, Saitama, Japan More articles by this author Akinori Sato Tokorozawa, Saitama, Japan More articles by this author Keiichi Ito Tokorozawa, Saitama, Japan More articles by this author Kenji Seguchi Tokorozawa, Saitama, Japan More articles by this author Makoto Sumitomo Tokorozawa, Saitama, Japan More articles by this author Tomohiko Asano Tokorozawa, Saitama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Immunohistochemistry for the detection of renal cell carcinoma in effusion cytology

Renal cell carcinoma (RCC) is known for its unpredictable behavior. RCC rarely involves serosal surfaces and, when present, can be difficult to distinguish from mesothelial cells in cytologic preparations. Immunohistochemical stains are frequently used with effusion cytology; however, RCCs express traditional glandular antigens less frequently than other adenocarcinomas. We investigated the utility of typical immunohistochemical stains for identifying effusion involvement by RCC, along with more specific RCC markers. The cytology databases from two academic institutions were searched for all effusions involved by RCC with retrievable cell-block material. A four-marker immunohistochemical panel we generally use for distinguishing adenocarcinoma from mesothelial proliferations was then applied (calretinin, WT1, MOC31, and B72.3). In addition, each case was stained for RCC antigen, CD10, and PAX2. Eleven cases of RCC involving serous effusions were identified: six conventional clear-cell RCCs, three papillary RCCs, and two RCCs, not otherwise specified. Neoplastic cells were positive for MOC-31 in 3 of 11 cases, RCC antigen in 5 of 11 cases, and CD10 in 10 of 11 cases. RCC cells were negative for B-72.3, WT1, and calretinin in all cases. Background mesothelial cells showed high-background cytoplasmic staining for PAX-2; all RCC tumor cells were negative or equivocal. A conventional panel used for the diagnosis of adenocarcinoma in fluids will fail to detect most cases of metastatic RCC, particularly clear-cell RCC. Additional antibodies, such as those to CD10 and RCC, may be helpful to identify these tumors. PAX2 shows high background in mesothelial cells, which makes interpretation of nuclear staining difficult.

Renal Oncocytosis: Management and Clinical Outcomes

Renal oncocytosis is a rare pathological condition in which renal parenchyma is diffusely involved by numerous oncocytic nodules in addition to showing a spectrum of other oncocytic changes. We describe our experience with renal oncocytosis, focusing on management and outcomes. A total of 20 patients with a final pathological diagnosis of renal oncocytosis from July 1995 through June 2009 were included in the analysis. Patient demographics, intraoperative variables and postoperative outcomes are reported. Median age at nephrectomy was 71 years (IQR 59-75). Of the patients 15 (75%) had bilateral disease. There were 23 operations (9 right side, 14 left side) performed on 20 patients, and of these procedures 13 (57%) were partial nephrectomies and 10 (43%) were radical nephrectomies. Median dominant tumor mass diameter was 4.1 cm (IQR 3-6.4, range 1 to 14.6). The most common dominant tumor histology was hybrid tumor between oncocytoma and chromophobe renal cell carcinoma in 13 of 23 specimens (57%), followed by chromophobe renal cell carcinoma in 6 (26%), oncocytoma in 3 (13%) and conventional renal cell carcinoma in 1 (4%). Ten patients (50%) had preexisting chronic kidney disease before nephrectomy and chronic kidney disease developed in 5 more after surgery. After a median followup of 35 months no patients had metastatic disease. Patients with renal oncocytosis usually present with multiple and bilateral renal nodules. Half of the patients had chronic kidney disease at diagnosis and 25% had new onset of chronic kidney disease. No patient had distant metastatic disease during followup. Our management approach is to perform partial nephrectomy when possible and then use careful surveillance of the remaining renal masses.

Glutathione S‐transferases as molecular markers of tumour progression and prognosis in renal cell carcinoma

Renal cell carcinoma (RCC) often recurs as distant metastasis; there is thus a need for new indicators to identify high-risk patients. Glutathione S-transferases (GST)-α and -π are involved in the renal bioactivation of toxic metabolites. The aim was to investigate whether their expression is of diagnostic and prognostic value. Western blotting of microdissected normal kidney and immunostaining of histological RCC microarrays shows expression of GST-α in proximal tubular cells, while GST-π was found in the distal nephron. Of the primary 174 RCC cases examined, GST-α immunoreactivity was restricted to conventional RCC (n=76, 68% positive) and was not seen in any other RCC subtypes. The cross-tabulation of the GST-α scores with other prognostic indices demonstrated that GST-α immunostaining was significantly more frequent in low-grade tumours (χ(2): P<0.004), and that conventional GST-α-positive RCC patients had a mean disease-free survival of 6.0 years (95% confidence interval 5.33-6.63), compared with 4.7 years (3.54-5.90) in GST-α-negative tumours (Kaplan-Meier survival analysis, P=0.011, log-rank test). GST-α is a highly specific diagnostic marker for primary conventional RCC, where it is a prognostic marker if grade is omitted from the multivariate analysis.

Detection of the TNFSF members BAFF, APRIL, TWEAK and their receptors in normal kidney and renal cell carcinomas.

In advanced renal cell carcinoma (RCC), surgery combined with systemic chemotherapy and immunotherapy have had limited effectiveness. Therapeutic modalities targeting VEGF, PDGF, and c-kit using tyrosine kinase inhibitors and m-TOR using specific biologic factors are in development. Therapeutic approaches targeting TNF-alpha have shown limited efficacy, while anti-TRAIL (TNFSF10) antibodies have shown enhanced activity. The presence and potential significance of other members of the TNFSF has not been investigated. Here, we assayed the TNFSF members APRIL, BAFF, TWEAK and their receptors (BCMA, TACI, BAFFR, Fn14) in 86 conventional type clear cell RCC, using immunohistochemistry and correlated our findings with histological data and, in a limited series, follow-up of patients. We observed a differential expression of these TNFSF ligands and receptors in cancerous and non-cancerous structures. BAFF was found in all RCC; APRIL expression is associated with an aggressive phenotype, correlating negatively with patients' disease-free survival, while TWEAK and its receptor Fn14 are heterogeneously expressed, correlating negatively with the grade and survival of RCC patients. This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and RCC, suggesting a potential role of these TNFSF members in renal tumor biology.

Detection of The TNFSF Members BAFF, APRIL, TWEAK and Their Receptors in Normal Kidney and Renal Cell Carcinomas

In advanced renal cell carcinoma (RCC), surgery combined with systemic chemotherapy and immunotherapy have had limited effectiveness. Therapeutic modalities targeting VEGF, PDGF, and c-kit using tyrosine kinase inhibitors and m-TOR using specific biologic factors are in development. Therapeutic approaches targeting TNF-alpha have shown limited efficacy, while anti-TRAIL (TNFSF10) antibodies have shown enhanced activity. The presence and potential significance of other members of the TNFSF has not been investigated. Here, we assayed the TNFSF members APRIL, BAFF, TWEAK and their receptors (BCMA, TACI, BAFFR, Fn14) in 86 conventional type clear cell RCC, using immunohistochemistry and correlated our findings with histological data and, in a limited series, follow-up of patients. We observed a differential expression of these TNFSF ligands and receptors in cancerous and non-cancerous structures. BAFF was found in all RCC; APRIL expression is associated with an aggressive phenotype, correlating negatively with patients' disease-free survival, while TWEAK and its receptor Fn14 are heterogeneously expressed, correlating negatively with the grade and survival of RCC patients. This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and RCC, suggesting a potential role of these TNFSF members in renal tumor biology.

The Relationship between B7-H4 Expression and Clinicopathological Characteristics in Clinical Stage T1 Conventional Renal Cell Carcinoma

PurposeThe diagnosis of clinically early-stage (T1) renal cell carcinoma (RCC) has increased. The present study evaluated the association of B7-H4 expression on the pathological outcome and recurrence of carcinoma in the T1 stage of RCC.Materials and MethodsAmong patients who underwent partial or radical nephrectomy after diagnosis of T1 stage RCC during the period of January 2000 to March 2007, 102 pathologically confirmed cases of clear cell carcinoma were included in this study. The patients' medical records were reviewed retrospectively. For the immunohistochemical staining tests, the B7-H4 antibody (Abbiotec 1:500) was used, and clinicopathological characteristics were analyzed.ResultsThe mean age of the patients (39 males: 38.2%, 63 females: 61.8%) was 53.0±12.0 years (range, 31-74 years), and the mean follow-up time was 33.4±21.0 months (range, 6-84 months). B7-H4 expression was positive in 18 cases and negative in 84 cases. Recurrence during the follow-up period occurred in 5 cases in the group with positive B7-H4 expression and in 7 cases in the group with negative B7-H4 expression, respectively (p=0.035). In the univariate analysis, a statistically significant relationship was observed only for the presence of B7-H4 expression (p=0.0019). In the multivariate analysis, other than the expression of B7-H4, cancer size and TNM stage had effects on the recurrence of cancer.ConclusionsFor clear cell RCC, B7-H4 expression had a critical impact on the prognosis of the patients, particularly on the recurrence of the carcinoma in patients with clinical stage T1 RCC.

Lack of KISS1R expression is associated with rapid progression of conventional renal cell carcinomas

The mortality of patients with conventional renal cell carcinomas (RCC) correlates directly with the development of metastasis, which cannot be reliably predicted simply by TNM classification. The aim of this study was to identify genes associated with the tumour progression. We have analysed the global gene expression in conventional RCCs, including those with and without progression by Affymetrix GeneChip and selected the genes by gene set enrichment analysis. The expression and function of KISS1R was validated by RT-PCR, western blotting and immunohistochemistry and by in vitro experiments. An immunohistochemical and clinical follow-up study showed that lack of KISS1R expression is associated with rapid progression of tumours. In vitro studies showed that activation of KISS1/KISS1R signalling by kisspeptin treatment decreases the motility and invasive capacity of tumour cells. The kisspeptin treatment also induces the expression of KISS1R in tumour cells in vitro and activates signalling in cases without constitutional expression of the receptor. Expression of the KISS1R protein can be used for estimating the prognosis of conventional RCCs. Confirming the activation of KISS1R signalling in vivo may open a way for kisspeptin treatment of patients with conventional RCCs.

Urological malignancies: one-year audit from a tertiary referral centre

Objective: To study the clinicopathological characteristics of urological malignancies. Patients and Method: Newly diagnosed patients with urological malignancies in the year 2009 in a single urological unit of a tertiary referral centre were included in this retrospective study. Results: During the study period there were 35 patients with carcinoma of the bladder; 17 patients with carcinoma of the prostate; 9 patients with renal malignancy; 1 patient with synchronous transitional cell carcinoma of the bladder and upper urinary tract; 1 patient with seminoma of the testis. Median age of the patients with primary bladder carcinoma was 65 years (range 46-82 years). Majority of the patients with primary bladder cancer were males (3.1:1) and had non-muscle invasive bladder cancer (72.7%). All patients with primary bladder cancer except one had transitional cell carcinoma (97%). Median age of the patients with carcinoma of the prostate was 70 years (range 60-81 years). All patients with carcinoma of the prostate had advanced disease at presentation. Median age of the patients with renal cell carcinoma (RCC) was 65 years (range 53-72 years). There is a 1.3:1 predominance of men over women. 85% of renal cell carcinomas were conventional renal cell carcinomas. Conclusion: Multicentre long-term studies are required to ascertain the actual clinicopathological characteristics of urological malignancies. DOI: 10.4038/slju.v10i1.2414Sri Lanka Journal of Urology, 2009, 10, 24-27

Differentially expressed micro-RNAs in clear cell renal cell carcinoma

Genomic studies of the past two decades have strongly suggested that the short arm of chromosome 3 contains several tumour suppressor genes contributing to conventional renal cell carcinoma (cRCC) development. Several candidate genes from 3p, including VHL, RASSF1A and FHIT, have been tested for their tumour-suppressor capacity. Although it is clear that these genes are involved in the development of a subset of solid tumours, at the same time it is evident that they do not explain everything. Recently it has become clear that, apart from protein coding transcripts, microRNAs can also exert tumour suppressor-like functions.

Characteristics and prognosis of chromophobe non‐metastatic renal cell carcinoma: A multicenter study

To analyze the characteristics and the prognostic significance of chromophobe renal cell carcinomas (chRCC). Data about 2981 patients with non-metastatic renal cell carcinomas (RCC) at the time of surgery were retrospectively collected from 26 institutions between 1998 and 2008. All patients had undergone partial or radical nephrectomies. Of the 2981 patients, 2602 patients with conventional RCC (cRCC) and 148 with chRCC were studied. Clinical and pathological parameters were determined in all patients. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed. Patients with chRCC differed significantly from those with cRCC on the following parameters: younger age (P=0.026), greater female ratio (P<0.001), and larger tumor diameter (P<0.001). Both groups were alike with respect to body mass index (P=0.943), Eastern Cooperative Oncology Group performance status (P=0.163), T stage (P=0.375), and Fuhrman's grade (P=0.134). The 5-year RFS rates in patients with chRCC and cRCC were 82.7% and 83.3%, respectively (P=0.762). The 5-year CSS rates in patients with chRCC and cRCC were 88.8% and 92.2%, respectively (P=0.980). Both groups showed equivalent oncological outcomes in terms of RFS and CSS for cases stratified by T stage and Fuhrman's grade. In multivariate analysis, the histological subtype was not retained as an independent prognostic variable (RFS: P=0.893; CSS: P=0.729). Despite being significantly different from cRCC in terms of several clinical and pathological parameters, chRCC shows equivalent oncological outcomes.

Expression of cholinesterases in human kidney and its variation in renal cell carcinoma types

Despite the aberrant expression of cholinesterases in tumours, the question of their possible contribution to tumorigenesis remains unsolved. The identification in kidney of a cholinergic system has paved the way to functional studies, but details on renal cholinesterases are still lacking. To fill the gap and to determine whether cholinesterases are abnormally expressed in renal tumours, paired pieces of normal kidney and renal cell carcinomas (RCCs) were compared for cholinesterase activity and mRNA levels. In studies with papillary RCC (pRCC), conventional RCC, chromophobe RCC, and renal oncocytoma, acetylcholinesterase activity increased in pRCC (3.92 ± 3.01 mU·mg(-1), P = 0.031) and conventional RCC (2.64 ± 1.49 mU·mg(-1), P = 0.047) with respect to their controls (1.52 ± 0.92 and 1.57 ± 0.44 mU·mg(-1)). Butyrylcholinesterase activity increased in pRCC (5.12 ± 2.61 versus 2.73 ± 1.15 mU·mg(-1), P = 0.031). Glycosylphosphatidylinositol-linked acetylcholinesterase dimers and hydrophilic butyrylcholinesterase tetramers predominated in control and cancerous kidney. Acetylcholinesterase mRNAs with exons E1c and E1e, 3'-alternative T, H and R acetylcholinesterase mRNAs and butyrylcholinesterase mRNA were identified in kidney. The levels of acetylcholinesterase and butyrylcholinesterase mRNAs were nearly 1000-fold lower in human kidney than in colon. Whereas kidney and renal tumours showed comparable levels of acetylcholinesterase mRNA, the content of butyrylcholinesterase mRNA was increased 10-fold in pRCC. The presence of acetylcholinesterase and butyrylcholinesterase mRNAs in kidney supports their synthesis in the organ itself, and the prevalence of glycosylphosphatidylinositol-anchored acetylcholinesterase explains the splicing to acetylcholinesterase-H mRNA. The consequences of butyrylcholinesterase upregulation for pRCC growth are discussed.