Chromophobe Renal Cell Cancer Research Articles

Prognostic role of the endothelial cell-specific molecule-1 histopathologic expression in renal cell cancer.

To measure the level of endothelial cell-specific molecule-1 (ESM-1) expression among the Renal Cell Cancer (RCC) variants using by immunohistochemical method and determine the relationship between ESM-1 expression and RCC prognosis. ESM-1 immunoreactivity scores (IR) were measured in appropriate renal tumoral tissue blocks of 153 consecutive RCC patients in this retrospective analysis of prospectively collected data. Mean ESM-1 IR scores were calculated in patients who were pathologically diagnosed with clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). Progression-free survival and overall survival were evaluated using the log-rank test according to ESM-1 IR scores. Survival rates were calculated using Kaplan-Meier survival analysis. In the ccRCC group, the mean ESM-1 IR scores of those with local invasion were significantly higher than those without local invasion (P = 0.014). The mean ESM-1 IR score of patients with metastatic ccRCC was significantly higher than those with non-metastatic ccRCC (P < 0.001). Considering all patients regardless of RCC subtype pathologies, the mean ESM-1 IR score in clinical stage 1 tumor was 3.82 ± 1.98, 4.87 ± 1.74 in clinical stage 2, 5.88 ± 2 in clinical stage 3, and 6.60 ± 2.23 in clinical stage 4. The mean ESM-1 IR score of patients with metastatic ccRCC was significantly higher than those with non-metastatic ccRCC (P < 0.001). The mean follow-up period for all patients in this study was 71 months (range 1-120 months). It has been shown that the higher the ESM-1 IR score, the lower the 10-year overall survival and disease-free survival rates (P = 0.026, P = 0.005). Immunohistochemical expression of ESM-1 may be a promising prognostic biomarker in RCC. Currently, some prognostic scoring systems are available for patients with localized and metastasized RCC. Incorporating ESM-1 expression in RCC into these existing prognostic scoring systems could improve these models and enhance the quality of individual oncologic management in RCC patients.

A rare case of a retrocrural lymph node metastasis from a chromophobe renal cell cancer: complete thoracoscopic resection with a new multi-joint articulating surgical instrument

We report a rare case of a 69-year-old man with a solitary retrocrural lymph node metastasis in the posterior mediastinum of an oligo-metastatic chromophobe renal cell cancer that was radically resected in a curative intent using new articulating Artisential® instruments.

CT-based radiomics for differentiating renal tumours: a systematic review.

Differentiating renal tumours into grades and tumour subtype from medical imaging is important for patient management; however, there is an element of subjectivity when performed qualitatively. Quantitative analysis such as radiomics may provide a more objective approach. The purpose of this article is to systematically review the literature on computed tomography (CT) radiomics for grading and differentiating renal tumour subtypes. An educational perspective will also be provided. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed. PubMed, Scopus and Web of Science were searched for relevant articles. The quality of each study was assessed using the Radiomic Quality Score (RQS). 13 studies were found. The main outcomes were prediction of pathological grade and differentiating between renal tumour types, measured as area under the curve (AUC) for either the receiver operator curve or precision recall curve. Features extracted to predict pathological grade or tumour subtype included shape, intensity, texture and wavelet (a type of higher order feature). Four studies differentiated between low-grade and high-grade clear cell renal cell cancer (RCC) with good performance (AUC = 0.82-0.978). One other study differentiated low- and high-grade chromophobe with AUC = 0.84. Finally, eight studies used radiomics to differentiate between tumour types such as clear cell RCC, fat-poor angiomyolipoma, papillary RCC, chromophobe RCC and renal oncocytoma with high levels of performance (AUC 0.82-0.96). Renal tumours can be pathologically classified using CT-based radiomics with good performance. The main radiomic feature used for tumour differentiation was texture. Fuhrman was the most common pathologic grading system used in the reviewed studies. Renal tumour grading studies should be extended beyond clear cell RCC and chromophobe RCC. Further research with larger prospective studies, performed in the clinical setting, across multiple institutions would help with clinical translation to the radiologist's workstation.

Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets.

Renal cell cancer (RCC) involves three most recurrent sporadic types: clear-cell RCC (70–75%, CCRCC), papillary RCCC (10–15%, PRCC), and chromophobe RCC (5%, CHRCC). Hereditary cases account for about 5% of all cases of RCC and are caused by germline pathogenic variants. Herein, we review how a better understanding of the molecular biology of RCCs has driven the inception of new diagnostic and therapeutic approaches. Genomic research has identified relevant genetic alterations associated with each RCC subtype. Molecular studies have clearly shown that CCRCC is universally initiated by Von Hippel Lindau (VHL) gene dysregulation, followed by different types of additional genetic events involving epigenetic regulatory genes, dictating disease progression, aggressiveness, and differential response to treatments. The understanding of the molecular mechanisms that underlie the development and progression of RCC has considerably expanded treatment options; genomic data might guide treatment options by enabling patients to be matched with therapeutics that specifically target the genetic alterations present in their tumors. These new targeted treatments have led to a moderate improvement of the survival of metastatic RCC patients. Ongoing studies based on the combination of immunotherapeutic agents (immune check inhibitors) with VEGF inhibitors are expected to further improve the survival of these patients.

Aberrant expression of membranous carbonic anhydrase IX (CAIX) is associated with unfavorable disease course in papillary and clear cell renal cell carcinoma

ObjectiveAntibodies against carbonic anhydrase IX (CAIX) are often part of immunohistochemical panels used to assist renal cell cancer (RCC) subtyping. This study was undertaken to determine, whether assessing CAIX expression levels could provide additional prognostic information. Methods and materialsMore than 1,800 RCCs were analyzed in a tissue microarray (TMA) format for CAIX expression. All tumors had been reviewed and newly classified according to the WHO 2016 classification. ResultsMembranous CAIX expression revealed a “black and white” pattern that was strikingly dependent on the RCC subtype. In clear cell RCC, 89.2% of cancers showed strong positivity. The few clear cell RCC with lower CAIX expression levels were more likely to exhibit unfavorable tumor phenotype (p < 0.0001) and poor disease course (p = 0.0036). CAIX was completely absent in 99% of chromophobe RCC and in 100% of oncocytomas. In papillary RCC, 80.2% of cancers showed complete absence of CAIX staining. Papillary RCC with detectable CAIX expression had a less favorable tumor phenotype (p≤0.05) and worse disease outcome (p = 0.0176). These data are consistent with the concept, that “aberrant” CAIX staining – meaning absent or weak staining in a cancer expected to have a high level CAIX expression such as clear cell RCC or detectable CAIX expression in tumors that are typically CAIX negative such as papillary and chromophobe RCC – reflects biologic tumor dedifferentiation. ConclusionOur data demonstrate that CAIX is a highly useful diagnostic biomarker for RCC providing both diagnostic and prognostic information.

Comparative Analysis of Surgery, Thermal Ablation, and Active Surveillance for Renal Oncocytic Neoplasms

To compare oncological and procedural outcomes for renal oncocytic tumors treated with surgery, thermal ablation, or active surveillance. Clinical and pathologic data were collected for consecutive patients with a histologic diagnosis of oncocytoma, oncocytic neoplasm, or chromophobe renal cell cancer (chRCC) from 2003 to 2016. Independent pathology and radiology reviews were performed for this study. Of 171 patients, tumor histology included oncocytoma (n = 122), chRCC (n = 47), and oncocytic neoplasm not otherwise specified (n = 2). At the initial diagnosis, 67, 14, and 90 patients were treated with surgery, thermal ablation, and active surveillance. In 3 of 19 patients (16%) who had biopsy and subsequent surgery, diagnosis changed from oncocytoma to chRCC. The median follow-up was 39.9 months with no difference among choices of treatment modalities (P = .33). Of 90 patients who began active surveillance, 32 (36%) switched to active treatments (19 underwent thermal ablation and 13 underwent surgery). The median linear growth rate for patients on active surveillance was 1.2 mm/y. No patients who were managed with active surveillance developed metastatic renal cell cancer (mRCC). mRCC was identified in 3 patients and was the cause of death in 2 patients. Patients who developed metastatic disease presented with symptomatic tumors of >4 cm and were treated with immediate surgery. For oncocytic masses of ≤4 cm (n = 126), the 5-year cancer-specific survival was 100%. Renal oncocytic neoplasms have favorable oncological outcomes. Active surveillance is safe and is the preferred management for small (≤4 cm) oncocytic renal tumors in selected patients.

Outcomes of Metastatic Chromophobe Renal Cell Carcinoma (chrRCC) in the Targeted Therapy Era: Results from the International Metastatic Renal Cell Cancer Database Consortium (IMDC).

Background: Treatment outcomes are poorly characterized in patients with metastatic chromophobe renal cell cancer (chrRCC), a subtype of renal cell carcinoma.Objective: This retrospective series aims to determine metastatic chrRCC treatment outcomes in the targeted therapy era.Methods: A retrospective data analysis was performed using the IMDC dataset of 4970 patients to determine metastatic chrRCC treatment outcomes in the targeted therapy era.Results: 109/4970 (2.2%) patients had metastatic chrRCC out of all patients with mRCC treated with targeted therapy. These patients were compared with 4861/4970 (97.8%) clear cell mRCC (ccRCC) patients. Patients with metastatic chrRCC had a similar OS compared to patients with ccRCC (23.8 months (95% CI 16.7 – 28.1) vs 22.4 months (95% CI 21.4 – 23.4), respectively (p = 0.0908). Patients with IMDC favorable (18%), intermediate (59%) and poor risk (23%) had median overall survivals of 31.4, 27.3, and 4.8 months, respectively (p = 0.028).Conclusions: To the authors’ knowledge, this is the largest series of metastatic chrRCC patients and these results set new benchmarks for survival in clinical trial design and patient counseling. The IMDC criteria risk categories seem to stratify patients into appropriate favourable, intermediate, and poor risk groups, although larger patient numbers are required. It appears that outcomes between metastatic chrRCC and ccRCC are similar when treated with conventional targeted therapies. Patients with metastatic chrRCC can be treated with tyrosine kinase inhibitors and enrolled in clinical trials to further measure outcomes in this rare patient population.

Molecular and Genomic Profiling to Identify Actionable Targets in Chromophobe Renal Cell Cancer

Metastatic chromophobe renal cell cancer (chRCC) is a rare subtype of RCC with no standard treatment. We performed molecular profiling of 12 chRCC cases to identify alterations predictive of response to therapy. Tests included immunohistochemistry assays, fluorescence in situ hybridization, and next-generation sequencing. Analysis identified c-KIT overexpression in 6/9 (67%) samples analyzed, and loss of protein expression of RRM1 and MGMT in 11/12 (92%) and of PTEN in 7/12 samples (58%). Mutations of TP53, PTEN, APC, and VHL genes were identified. In summary, molecular profiling of chRCC identified alterations in genes and protein expression that might provide a mechanistic rationale for off-label use of approved therapies in advanced chRCC, and could guide the design of molecularly targeted clinical trials. Patient summaryIn this study, we evaluated samples of a rare type of kidney cancer (chromophobe type) and identified potential genetic markers that could be used to individualize treatment and possibly improve treatment outcomes.

Outcomes of metastatic chromophobe renal cell carcinoma (chrRCC) in the targeted therapy era: Results from the International Metastatic Renal Cell Cancer Database Consortium.

4570Background: Treatment outcomes are poorly characterized in patients with metastatic chromophobe renal cell cancer (chrRCC), a subtype of renal cell carcinoma. Methods: A retrospective data anal...

Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database

The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort. We queried the SEER (Surveillance, Epidemiology and End Results) 18-registry database for all patients 20 years old or older who were surgically treated for renal cell carcinoma between 2001 and 2008. Patients with unknown race, grade, stage or histology and those with multiple tumors were excluded from study. Four cohorts were created by dividing patients by gender, including 1,202 females and 1,715 males younger than 40 years old, and 18,353 females and 30,891 males 40 years old or older. Chi-square analysis was used to compare histological distributions between the cohorts. While clear cell carcinoma was still the most common renal cell cancer subtype across all genders and ages, chromophobe renal cell cancer was the most predominant type of nonclear renal cell cancer histology in young females, representing 62.3% of all nonclear cell renal cell cancers (p <0.0001). In all other groups papillary renal cell cancer remained the most common type of nonclear renal cell cancer. It is possible that hormonal factors or specific pathway dysregulations predispose chromophobe renal cell cancer to develop in younger women. We hope that this work provides some new observations that could lead to further studies of gender and histology specific renal tumorigenesis.

MP50-06 COMPARATIVE ANALYSIS OF SMOKING AS A RISK FACTOR AMONG RENAL CELL CARCINOMA HISTOLOGIC SUBTYPES

You have accessJournal of UrologyKidney Cancer: Evaluation and Staging III1 Apr 2015MP50-06 COMPARATIVE ANALYSIS OF SMOKING AS A RISK FACTOR AMONG RENAL CELL CARCINOMA HISTOLOGIC SUBTYPES Neel Patel, Kristopher Attwood, Terrance Creighton, Diana Mehedint, Michael Hanzly, Thomas Schwaab, and Eric Kauffman Neel PatelNeel Patel More articles by this author , Kristopher AttwoodKristopher Attwood More articles by this author , Terrance CreightonTerrance Creighton More articles by this author , Diana MehedintDiana Mehedint More articles by this author , Michael HanzlyMichael Hanzly More articles by this author , Thomas SchwaabThomas Schwaab More articles by this author , and Eric KauffmanEric Kauffman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1671AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Smoking is the best established modifiable risk factor for renal cell cancer (RCC), but the risk for developing individual RCC histologic subtypes with smoking is unknown. We investigated the relationship between smoking and RCC subtype. METHODS Smoking data was collected from 819 consecutive patients with either non-familial RCC (N=707) or benign pathology (N=112) undergoing nephrectomy at a single National Comprehensive Cancer Network cancer center, and retrospectively tested for statistical association with histologic diagnosis (benign, clear cell RCC, papillary RCC, chromophobe RCC or other RCC) in univariable and multivariable analyses. RESULTS A positive smoking history was reported by 51.4% of patients. Active smoking was nearly twice as common with clear cell (21.4%) or papillary (24.0%) RCC as with benign histology (12.5%, p<0.05 each), yet strikingly uncommon with chromophobe RCC (5.7%, p<0.05 vs. clear cell or papillary, Figure 1). Any smoking history (i.e., active or former) was similarly less common with chromophobe (31.5%) compared to clear cell (52.7%, p<0.05) or papillary (58.3%, p<0.05) RCC histology (Figure 1). Chromophobe RCC diagnosis was five times more likely if a patient was not actively smoking (p<0.01). Smoking extent (mean pack-years, mpy) was significantly greater with clear cell (14.6 mpy) or papillary (14.3 mpy), but not chromophobe RCC (9.3 mpy), compared to benign histology (8.7 mpy, Figure 2), and similar relationships were observed for mean packs per day. In multivariable analyses adjusting for age, gender, race, BMI, tumor size and stage, both clear cell and papillary but not chromophobe RCC were independently associated with active smoking (OR >2.0 each). CONCLUSIONS Traditional understanding of smoking as a RCC risk factor applies to the clear cell and papillary subtypes, but not the chromophobe subtype. These findings underscore distinct molecular carcinogenic mechanisms underlying the different RCC subtypes, and identify smoking as novel clinical variable aiding in RCC histologic subtype prediction. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e613 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neel Patel More articles by this author Kristopher Attwood More articles by this author Terrance Creighton More articles by this author Diana Mehedint More articles by this author Michael Hanzly More articles by this author Thomas Schwaab More articles by this author Eric Kauffman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Bilateral renal tumour as indicator for birt-hogg-dubé syndrome.

Birt-Hogg-Dubé (BHD) syndrome is a cancer disorder caused by a pathogenic FLCN mutation characterized by fibrofolliculomas, lung cysts, pneumothorax, benign renal cyst, and renal cell carcinoma (RCC). In this case we describe a patient with bilateral renal tumour and a positive familial history for pneumothorax and renal cancer. Based on this clinical presentation, the patient was suspected for BHD syndrome, which was confirmed after molecular testing. We discuss the importance of recognizing this autosomal dominant cancer disorder when a patient is presented at the urologist with a positive family history of chromophobe renal cell cancer or a positive familial history for renal cell cancer and pneumothorax.

Relevance of the clinical–pathological predictive factors in force in chromophobe renal cell cancer

IntroductionThe identification of new subtypes of renal cell carcinoma (RCC) has made it necessary to re-evaluate the current clinical and pathological predictive factors (stage, Fuhrman nuclear grade, necrosis, lymphovascular invasion [LVI] and sarcomatoid component) in these new subtypes. The chromophobe renal cell carcinoma (CRCC) is considered a less aggressive subtype of RCC. The purpose of this article is to evaluate the usefulness of current clinicopathologic predictors of RCC in our series of CRCC. Material and methodsWe retrospectively reviewed the clinicopathologic features of 63 patients with CRCC treated with radical nephrectomy. The parameters analyzed were tumor extension with the TNM, grade according to Fuhrman classification, LVI, tumor necrosis, tumor thrombus, surgical margin status, and involvement of the collecting system. The results (disease recurrence) were evaluated by Cox regression model with univariate and multivariate analysis. ResultsWith a median follow up of 60.2 months (0.37–160.2), 8 (11%) patients had recurrence, with median time to recurrence of 31.7 months (5.37–124.33). In the univariate analysis, TNM extension (p=0.0001), Fuhrman grade III or IV (p=0.031), LVI (p=0.0001) and the presence of positive surgical margins (p=0.0001) were statistically significant variables for recurrence. In the multivariate analysis, only tumor stage was confirmed as an independent predictor of recurrence, pT1 versus pT2 (p=0.02; OR 0.27; 95% CI 0.03–0.258) and pT2 versus higher stage (p=0.037; OR 0.173; 95% CI 0.033–0.896). ConclusionsThe tumor stage predicts aggressiveness in the CCRC. The classification of Fuhrman nuclear grade is not useful for this histological subtype.

Chromophobe renal cell cancer - review of the literature and potential methods of treating metastatic disease

Chromophobe renal cell carcinoma (ChRCC) is a subtype of renal cell carcinoma (RCC). ChRCC is diagnosed mainly in 6th decade of life. An incidence of ChRCC is similar in both men and woman. Eighty six percent of ChRCCs cases are diagnosed in stage 1 or 2. Prognosis of ChRCC is better than in other types of RCC. Five- and 10-year disease free survival (DFS) for ChRCC was 83.9% and 77.9%, respectively. Expression of immunohistological markers: cytokeratins (CK), vimentin, epithelial membrane antigen (EMA), CD10 could be potentially helpful in diagnosis of different subtypes of RCC. From all conventional RCC, CD 117 was detected (overexpression) in membrane of cells ChRCC.Overexpression of CD117 on cellular membranes of ChRCC could be a potential target for kinase inhibitors like: imatinib, dasatinib, nilotinib. The potential targets for other kinase inhibitors (sunitinib and sorafenib) in ChRCC seem to be VEGFR and PDGFR. On the basis for formulating research hypotheses which should be verified by prospective studies.

CD98hc (SLC3A2), a novel marker in renal cell cancer

In a variety of malignant diseases, molecular targeting represents a therapeutic option, whereby, when compared with chemotherapy, fewer side effects are thought to be expected. Especially in renal cell cancer (RCC), tyrosine kinase-inhibitors have been established as useful and highly effective therapy. However, tyrosine kinase-inhibitors currently approved for RCC treatment lack single molecule specificity and bear a variety of side effects of the gastro-intestinal tract, skin, heart and haematopoietic system. Therefore, the identification of novel cell surface markers is sought, which might lead to novel diagnostic and therapeutic strategies in cancer. Paraffin-embedded RCCs from a well characterized tissue bank were immunohistochemically quantified for embryonic transmembrane antigen CD98hc (SLC3A2) expression and semi-quantitative analyses were correlated with subtype or grade of differentiation. We found increased CD98hc expression in different types of malign RCCs, among them clear cell (cc)RCC, papillary (p)RCC and chromophobe (ch)RCC, but lack of expression in the benign renal oncocytoma. Thereby, the extent of CD98hc expression directly complies with grade of malignancy. Furthermore, the more malignant type II pRCC significantly higher expressed CD98hc than the less malignant and more differentiated type I pRCC (type II 83.34%, type I 4.76% CD98hc positive, P < 0.00001; n = 51). The established marker for type I pRCC, Cytokreatin 7, showed 95.24% expression in type I and 26.67% expression in type II pRCC (P < 0.00001, n = 51). From these data, we conclude that CD98hc is expressed in RCCs, whereby the extent of expression is likely to correlate directly with grade of malignancy. In pRCCs, CD98hc might represent a novel and reliable marker for type II pRCC.

Endopeptidase 24.11/CD10 is down-regulated in renal cell cancer.

The regulatory mechanisms responsible for malignant transformation, tumor progression and metastasis in renal cell cancer (RCC) are still unclear, but there is some evidence that biologically active peptides might have regulatory effects on the behavior of this malignancy. Tumor cells can change local concentrations of active peptides by modulating their cell-surface enzymes. Using immunohistochemistry and enzyme-histochemistry, the expression of various membrane peptidases was examined in RCC and adjacent noninvaded renal parenchyma (n = 44). We describe the down-regulation of neutral endopeptidase 24.11 (NEP) protein expression in RCC of the clear cell/chromophilic type when compared with renal parenchyma, and show for the first time the lack of enzyme activity of NEP in RCC. The strongest expression could be found for dipeptidyl peptidase IV (DPIV) which is only decreased in RCC of the chromophobe cell type and is even present in oncocytoma. Aminopeptidase N (APN) and aminopeptidase A (APA) show attenuated expression in up to one third of clear cell/ chromophilic RCC. Chromophobe RCC and oncocytomas do not express APN, APA, NEP and gamma-glutamyltranspeptidase.