Inflammatory Protein Serum Amyloid A1 Marks a Subset of Conventional Renal Cell Carcinomas with Fatal Outcome

Background

Conventional renal cell carcinoma (RCC) is the most common renal cancer. As the metastatic conventional RCC is practically incurable, there is a need for markers to estimate the tumour aggressiveness.

Objective

To identify and characterise new marker(s) associated with the poor prognosis of conventional RCC.

Design, Setting, and Participants

RNA from 24 conventional RCCs was analysed for global gene expression by Affymetrix U133 Plus 2.0 arrays. Tissue microarrays containing 224 renal tumours including 87 conventional RCCs were used for immunohistochemistry. Cell lines HD2, HD48, HA344 and HA465 established in our laboratory were used for invasion assay and zymography.

Measurements

Serum amyloid A 1 (SAA1) was found to be upregulated in conventional RCCs and it has been analysed by quantitative RT-PCR and immunohistochemistry on TMAs to establish the correlation between SAA1 protein expression and patient survival by uni and multivariate analysis. The effect of SAA1 on tumour cell behaviour in vitro has also been examined by invasion assay and zymography.

Results and Limitations

SAA1 RNA is expressed in conventional RCC samples of patients with poor prognosis. Immunohistochemistry of 72 conventional RCCs with a 5 yr follow up showed a correlation between SAA1 expression and the clinical outcome of disease. Stimulation of conventional RCC cell lines with recombinant SAA1 increased the expression of metalloproteinase (MMP)-9 and the invasive potential of tumour cells. Limitation of the study is a relatively small number (72) of patients having follow up.

Conclusion

SAA1 seems to be a useful marker to estimate the prognosis of conventional RCCs.     

Prognostic Value of Capsular Invasion for Localized Clear-Cell Renal Cell Carcinoma

Background

The impact of capsular invasion on the survival of patients undergoing surgery for renal cell carcinoma (RCC) has attracted little attention in the literature and remains controversial.

Objectives

To evaluate the value of capsular invasion, without perirenal fat invasion, on the prognosis of patients with localized clear-cell RCC.

Design, setting, and participants

Between 1984 and 2007, we retrospectively reviewed the records of 317 consecutive patients with localized clear-cell RCC (pT1–T2N0M0) who underwent radical nephrectomy or nephron-sparing surgery at our institution. Overall, 299 patients were eligible for the study. We analyzed clinical (presentation and body mass index [BMI]) and pathologic (tumor size, Fuhrman nuclear grade, collecting system invasion, microvascular invasion, and capsular involvement) parameters.

Measurements

Recurrence-free survival (RFS) and cancer-specific survival (CSS) were investigated using the Kaplan-Meier method, and the Cox regression model was used to determine the significant prognostic factors based on multivariate analysis.

Results and limitations

Renal capsular invasion was observed in 106 of 299 patients (35.5%). Capsular invasion had a statistically significant association with age, symptomatic presentation, tumor diameter, pathologic stage, collecting system invasion, and microvascular invasion. The mean follow-up was 60.5 mo (range: 1–249). The 5-yr RFS and CSS rates for tumors with capsular invasion were significantly lower compared with rates for tumors without invasion (77.7% vs 92.3% and 85.5% vs 95.7%, respectively; p = 0.0004). Multivariate analysis showed that BMI (hazard ratio [HR] = 0.19), stage (HR = 2.45), and capsular invasion (HR = 3.36) were independent prognostic factors of disease recurrence. With respect to CSS, BMI (HR = 0.20), tumor size (HR = 1.13), and capsular invasion (HR = 4.03) were the factors related to death. Nevertheless, we recognize that these findings may be limited by the study's retrospective, single-institution design.

Conclusions

Our findings suggest that capsular invasion is associated with poor survival in patients with localized clear-cell RCC.     

MicroRNA-15a expression measured in urine samples as a potential biomarker of renal cell carcinoma

Introduction

Currently, there is no accurate diagnostic molecular biomarker for renal cell carcinoma (RCC). The aim of this study was to assess the expression of microRNA-15a (miR-15a) in urine of patients with RCC and to evaluate its potential as a diagnostic molecular biomarker.

Materials and methods

In total, 67 patients with solid renal tumors were enrolled: clear-cell RCC (ccRCC, n?=?22), papillary RCC (pRCC, n?=?16), chromophobe RCC (chRCC, n?=?14), oncocytoma (n?=?8), papillary adenoma (n?=?2) and angiomyolipoma (n?=?5). MiRNA-15a expression levels measurement in urine were performed using qPCR. Urine of 15 healthy volunteers without kidney pathology was used as control.

Results

We observed a difference in mean miR-15a expression values in groups of pre-operative patients with RCC, benign renal tumors and healthy persons (2.50E?01?±?2.72E?01 vs 1.32E?03?±?3.90E?03 vs 3.36E?07?±?1.04E?07 RFU, respectively, p?<?0.01). There was no difference in miR-15a expression between ccRCC, pRCC and chRCC (p?>?0.05). Direct association between RCC size and miR-15a expression values was obtained (Pearson correlation coefficient—0.873). On the 8th day after nephrectomy, mean expression value in patients with RCC decreased by 99.53% (p?<?0.01). MiR-15a expression differentiated RCC from benign renal tumors with 98.1% specificity, 100% sensitivity at a cut-off value of 5.00E?06 RFU, with AUC—0.955.

Conclusions

MiR-15a expression measured in urine may be used as diagnostic molecular biomarker for RCC.

     

Reassessing the Current UICC/AJCC TNM Staging for Renal Cell Carcinoma

Context

The outcome prediction for renal cell cancer (RCC) remains controversial, and although many parameters have been tested for prognostic significance, only a few have achieved widespread acceptance in clinical practice. The TNM staging system defines local extension of the primary tumour (T), involvement of regional lymph nodes (N), and presence of distant metastases (M).

Objective

This review focuses on reassessing the current TNM staging system for RCC.

Evidence acquisition

A literature search in English was performed using the National Library of Medicine database and the following keywords: renal cell cancer, kidney neoplasm, and staging. We scrutinized 1952 references, and 62 were selected for review based on their pertinence, study size, and overall contribution to the field.

Evidence synthesis

The prognostic significance of tumour size for localized RCC has been investigated in a large number of studies. As a consequence, many modifications of the TNM staging system were primarily made to the size cut points between stage I and II tumours. The latest three revisions of the TNM system are systematically reviewed. For the heterogeneous group of locally advanced RCCs, involving different anatomic structures surrounding the kidney, the situation is still the subject of controversial scientific dispute. In detail, perirenal fat invasion, direct infiltration of the ipsilateral adrenal gland, invasion of the urinary collecting system, infiltration of renal sinus fat, and vena cava and renal vein thrombosis are disputed. Finally, staging of lymph node metastases and distant metastatic disease is discussed.

Conclusions

Special emphasis should be put on renal sinus invasion for stage evaluation. Retrospective studies relying on material collected at a time when no emphasis was placed on adequate sampling of the renal sinus should be treated with caution. In view of new treatment opportunities, the current TNM staging system of RCC and any other staging system must be dynamic.     

Carbonic Anhydrase IX in Renal Cell Carcinoma: Implications for Prognosis,Diagnosis, and Therapy

Context

The clinical management of patients with renal cell carcinoma (RCC) remains difficult, and the development of new diagnostic, prognostic, and therapeutic tools is still required.

Objective

To review the current knowledge on the RCC-associated antigen carbonic anhydrase IX (CAIX) and provide evidence for how this antigen may aid in the clinical management of RCC.

Evidence acquisition

Clinical papers describing diagnostic, prognostic, and/or therapeutic applications of CAIX in RCC were selected from the Pubmed database. The search was manually augmented by reviewing the reference lists of articles.

Evidence synthesis

Expression of CAIX is regulated by the Von Hippel Lindau (VHL) protein (pVHL). Because of the invariable VHL mutational loss in clear-cell RCC (ccRCC) patients, CAIX expression is ubiquitous in ccRCC. Determination of CAIX expression in nephrectomy specimens of RCC patients improves prognostic accuracy; high CAIX expression appears to correlate with a favourable prognosis and a greater likelihood of response to systemic treatment for metastatic disease. Therefore, CAIX expression might be used to stratify metastatic ccRCC (mRCC) patients for systemic treatment. When incorporated into the RCC nomogram, CAIX expression seems to improve diagnostic accuracy for primary RCC as well as mRCC patients, but further evidence is required. Clinical studies with the CAIX-specific monoclonal antibody (mAb) cG250 have provided unequivocal evidence that ccRCC lesions can be imaged with radiolabeled cG250. Results are awaited of a large, randomised trial that aims to establish the value of cG250 imaging for primary RCC. The outcome of another large, placebo-controlled study is awaited to establish the usefulness of CAIX-targeted therapy in the adjuvant setting. Therapeutic trials with high-dose radiolabeled cG250 and CAIX-loaded dendritic cells in mRCC patients are still in phase 1 or 2.

Conclusions

CAIX improves diagnostic accuracy and is an attractive target for imaging of and therapy for ccRCC.     

Differential expression of the sirtuin family in renal cell carcinoma: Aspects of carcinogenesis and prognostic significance

Objectives

Sirtuins (1–7) are evolutionarily conserved NAD-dependent deacetylases that play an important role in carcinogenesis. However, their role in renal cell carcinoma (RCC) remains unclear. The objective of the present study was to examine the role of SIRTs in RCC carcinogenesis and prognosis.

Hybrid Renal Cell Carcinomas Containing Histopathologic Features of Chromophobe Renal Cell Carcinomas and Oncocytomas Have Excellent Oncologic Outcomes

Background

Modern histopathology is able to differentiate chromophobe renal cell carcinomas (cRCCs), oncocytomas, and chromophobe–oncocytic hybrid RCCs; however, the true frequency and clinical courses of these tumors remain unclear.

Objective

To determine the clinical course of hybrid RCC.

Design, setting, and participants

Ninety-one surgically treated tumors, originally classified as oncocytoma or cRCC, were slide reviewed and reclassified by an experienced uropathologist. Immunohistochemical cytokeratin-7 (CK7) staining was used to distinguish oncocytoma (CK7 positive in <10% of the cells) and hybrid RCCs (CK7 positive in >10% of the cells).

Interventions

Radical tumor nephrectomy or nephron-sparing surgery.

Measurements

Recurrence-free and tumor-specific survival.

Results and limitations

Overall, 16 tumors (17.6%) were hybrid RCCs, 32 tumors were cRCCs, and 43 tumors were pure oncocytomas. Perinephric tissue invasion (pT3a) was found in one pure oncocytoma and in two hybrid RCCs. The pathologic stage for cRCC was pT1 in 50% of tumors (n = 17), pT2 in 23.5% of tumors (n = 8), and pT3a in 26.5% of tumors (n = 9). Low-grade RCC was found in 76.5% of tumors (n = 26), and vascular invasion was found in 11.8% of tumors (n = 4). After a mean follow-up of 50 mo, no oncocytomas or hybrid RCCs were found, but two cRCCs had recurred. The 3-yr tumor-specific survival rates for patients with oncocytoma, hybrid RCCs, and cRCC were 100%, 100%, and 97%, respectively.

Conclusions

Hybrid RCCs are more common than expected. The survival rate is 100% for both hybrid RCCs and oncocytomas. Hybrid RCCs may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses.     

Differential expression and clinical relevance of MUC1 in renal cell carcinoma metastasis

Purpose

To determine the differential expression patterns and prognostic relevance of Mucin-1 (MUC1) expression in clear cell renal cell carcinoma (RCC) metastasis.

Methods

Tissue microarrays (TMA) from samples of 151 RCC metastases, 61 primary RCCs and corresponding benign renal tissues were immunohistochemically stained for MUC1 and semi-quantitatively evaluated by immunoreactivity scores (IRS). MUC1 differential expression in metastasis, primary RCC and normal tissue were comparatively analyzed. Patient characteristics and clinical follow-up for patients with metastatic RCC (mRCC) were recorded. Correlations of MUC1 expression with mRCC survival were determined.

Results

Median cytoplasmic expression was highest in benign tissue (IRS = 1.04). Primary RCC (0.50) and metastasis (0.12) showed significantly lower cytoplasmic staining intensity. Membranous expression in benign tissue was, however, significantly lower (0.21) compared with primary RCC (0.59) and metastasis (0.57). Notable differences of MUC1 cytoplasmic and membranous expression were observed between different metastasis sites. Significantly higher (P = 0.014) membranous expression was observed in pulmonary versus non-pulmonary lesions, while no significant differences of cytoplasmic MUC1 expression were observed. The prognostic relevance of MUC1 expression in metastatic RCC was limited.

Conclusions

MUC1 is differentially expressed in benign renal tissue, primary RCC and RCC metastasis. Membranous MUC1 expression was significantly elevated in pulmonary metastases compared to non-pulmonary lesions, which may reflect individual biology and putative response to MUC1-based anti-cancer therapy.

     

A preoperative prognostic model for patients treated with nephrectomy for renal cell carcinoma

Background

Currently two pretreatment prognostic models with limited accuracy (65–67%) can be used to predict survival in patients with localized renal cell carcinoma (RCC).

Objective

We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC.

Design, setting, and participants

The data originated from a series of prospectively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006. Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers.

Measurements

The probability of RCC-specific mortality was modeled using Cox regression. The significance of the predictors was confirmed using competing risks analyses, which account for mortality from other causes.

Results and limitations

Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts, respectively. The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4% at 5 yr after nephrectomy and 68.3% at 10 yr after nephrectomy. All variables except gender achieved independent predictor status. In the external validation cohort the nomogram predictions were 88.1% accurate at 1 yr, 86.8% accurate at 2 yr, 86.8% accurate at 5 yr, and 84.2% accurate at 10 yr.

Conclusions

Our model substantially exceeds the accuracy of the existing pretreatment models. Consequently, the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC.     

Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma

Background

Animal models are instrumental in understanding disease pathophysiology and mechanisms of therapy action and resistance in vivo.

Objective

To establish and characterize a panel of mouse models of renal cell carcinoma (RCC) derived from patients undergoing radical nephrectomy.

Design, setting, and participants

In vivo and in vitro animal experiments.

Measurements

Tumor tissues obtained during surgery were implanted into the subcutaneous space of female BALB/c nude mice and serially passaged into new mice. Tumors were characterized by histology, short tandem repeat (STR) fingerprinting, von Hippel-Lindau (VHL) gene sequencing, and single nucleotide polymorphism (SNP) analysis. Tumor-bearing mice were treated with sunitinib or everolimus. Primary cell cultures were derived from patient tumors and transfected with a lentivirus carrying the luciferase gene. Four subcutaneous xenograft mouse models were developed, representing papillary type 1, papillary type 2, clear cell, and clear cell with sarcomatoid features RCC.

Results and limitations

RCC mouse models were established from four patients with distinct histologies of RCC. Tumor growth was dependent on histologic type, the size of the implanted tumor chip, and the passage number. Mouse tumors accurately represented their respective original patient tumors, as STR fingerprints were matching, histology was comparable, and SNP profiles and VHL mutation status were conserved with multiple passages. Bioluminescence imaging results were commensurate with subcutaneous xenograft growth patterns. Mice treated with sunitinib and everolimus exhibited an initial response, followed by a later stage of resistance to these agents, which mimics the clinical observations in patients with RCC.

Conclusions

We developed four mouse xenograft models of RCC with clear-cell and papillary histologies, with stable histologic and molecular characteristics. These models can be used to understand the basic biology of RCC as well as response and resistance to therapy.     

Hereditary Renal Cancer Syndromes: An Update of a Systematic Review

Context

Hereditary renal cancers (HRCs) comprise approximately 3–5% of renal cell carcinomas (RCCs).

Objective

Our aim was to provide an overview of the currently known HRC syndromes in adults.

Evidence acquisition

Data on HRC syndromes were analysed using PubMed and Online Mendelian Inheritance in Man with an emphasis on kidney cancer, clinical criteria, management, treatment, and genetic counselling and screening.

Evidence synthesis

Ten HRC syndromes have been described that are inherited with an autosomal dominant trait. Eight genes have already been identified (VHL, MET, FH, FLCN, TSC1, TSC2, CDC73, and SDHB). These HRC syndromes involve one or more RCC histologic subtypes and are generally bilateral and multiple. Computed tomography and magnetic resonance imaging are the best imaging techniques for surveillance and assessment of renal lesions, but there are no established guidelines for follow-up after imaging. Except for hereditary leiomyomatosis RCC tumours, conservative treatments favour both an oncologically effective therapeutic procedure and a better preservation of renal function.

Conclusions

HRC involves multiple clinical manifestations, histologic subtypes, genetic alterations, and molecular pathways. Urologists should know about HRC syndromes in the interest of their patients and families.     

Simple Enucleation for the Treatment of PT1a Renal Cell Carcinoma: Our 20-Year Experience

Objectives

To evaluate the safety and efficacy of simple enucleation as a conservative treatment for pT1a RCC, and to report on the incidence of major complications, local recurrence, and progression-free and disease-specific survival rates.

Methods

We retrospectively reviewed the data of 232 patients who had nephron-sparing surgery (NSS) by simple enucleation between 1986 and 2004 for sporadic, unilateral, pathologically confirmed pT1a RCC. The patients’ status was evaluated last in September 2005. The mean (median, range) follow-up was 76 (61, 12–225) months.

Results

The mean (SD, median, range) tumor greatest dimension was 2.8 (0.78, 2.85, 0.6–4) cm. The histopathologic review according to the International Union Against Cancer and American Joint Commission for Cancer (1997) classification revealed 198 clear cell (85.3%), 18 papillary (7.8%), 15 chromophobe (6.5%) and one (0.4%) collecting duct RCCs. There were no major complications, such as prolonged acute tubular necrosis/chronic renal insufficiency and bleeding requiring open reoperation. One patient developed postoperative late retroperitoneal fluid collection consistent with urinoma, which required aspiration, drainage position and JJ stenting for 3 weeks. The 5- and 10-year cancer-specific survival were 96.7% and 94.7%, respectively. The 5- and 10-year progression-free survival were 96% and 94%, respectively. Overall, 13 (6.4%) patients had disease progression, three of whom had local recurrences alone (1.5%) elsewhere in the kidney; none had local recurrence at the level of the enucleation bed.

Conclusions

Simple tumor enucleation is a safe and acceptable nephron-sparing treatment that provides excellent long-term local control and cancer-specific survival rates.     

A Proposal for Reclassification of the Fuhrman Grading System in Patients with Clear Cell Renal Cell Carcinoma

Background

The conventional Fuhrman grading system, which categorizes renal cell carcinoma (RCC) with grades I, II, III, and IV, is the most widely used predictor assessment of RCC cancer-specific mortality (CSM).

Objectives

The aim of this study was to test the prognostic ability of simplified Fuhrman grading schemes (FGSs) that rely on two- or three-tiered classifications.

Design, setting, and participants

The current study addressed a population of 14 064 patients with clear cell RCC who were treated with partial or radical nephrectomy between 1988–2004, within nine Surveillance, Epidemiology, and End Results (SEER) cancer registries.

Measurements

Univariable and multivariable analyses as well as prognostic accuracy analyses were performed for various FGSs to test their ability to predict CSM rates. The conventional four-tiered FGS was compared to a modified two-tiered FGS in which grades I and II and grades III and IV were combined. A second simplified three-tiered FGS in which grades I and II were combined but grades III and IV were kept separate was also tested.

Results and limitations

The overall 5-yr CSM-free rate was 81.5%. All three FGSs achieved independent predictor status in multivariable analyses. Prognostic accuracy of multivariable models that relied on various FGSs was 83.6% for the modified two-tiered FGS and 83.8% for both the conventional four-tiered and the modified three-tiered FGS.

Conclusions

Our findings indicate that the simplified FGSs perform equally as well as the conventional four-tiered FGS. The use of simplified grading schemes may represent an advantage for pathologists as well as for clinicians caring for patients with RCC.     

Is There a Need to Further Subclassify pT2 Renal Cell Cancers as Implemented by the Revised 7th TNM Version?

Background

The recently modified TNM classification of renal cell carcinoma (RCC) (7th edition) has implemented a subdivision of pT2 tumours into stage pT2a (>7 or ≤10 cm) versus pT2b disease (>10 cm).

Objective

Our aim was to evaluate whether this subdivision of pT2 RCC is justified due to a clinical prognosis divergence between the two groups (pT2a vs pT2b)

Design, setting, and participants

In total, 5122 patients were subjected to either radical nephrectomy or nephron-sparing surgery at three centres in Germany (University Hospitals of Hannover, Homburg/Saar, and Marburg). Patients were reclassified into stage pT2a and pT2b according to the maximum tumour diameter as suggested by the 7th revised version of the TNM classification system.

Measurements

The t test and Fisher exact test were applied to evaluate the comparability of the two groups (pT2a vs pT2b) regarding several additional patients’ and tumour-specific characteristics of known prognostic relevance for RCC. Univariable (Kaplan-Meier analysis) and multivariable statistical analyses (Cox proportional hazards regression model) were applied to identify a possible difference between the two groups (pT2a vs pT2b) regarding cancer-specific survival (CSS).

Results and limitations

Applying the new TNM classification, 579 previously pT2-staged patients were divided into 445 (76.9%) with pT2a and 134 (23.1%) with pT2b tumours. Kaplan-Meier curves revealed no significant difference in CSS between pT2a and pT2b patients; 5-yr CSS was 79.0% and 74.1%, respectively (p = 0.38). When applying multivariable analysis, unlike tumour grade and N/M status, pT2 subclassification failed to independently predict survival in RCC patients.

Conclusions

The new subclassification of pT2 RCC into two different subgroups as suggested by the latest modification of the TNM system does not yield additional/prognostic information.     

A review of integrated staging systems for renal cell carcinoma

Context

Several outstanding integrated staging systems (ISSs) have been devised for patients with renal cell carcinoma (RCC).

Objective

To review the available literature on existing ISSs.

Evidence acquisition

A nonsystematic search was conducted using Medline and PubMed databases. Original articles, review articles, and editorials addressing the development and validation of ISSs in RCC published up to February 2012 were identified. The search was limited to the English language. Keywords included kidney cancer, renal cell carcinoma, nomogram, risk group, prognosis, predictive accuracy, external validation, and discrimination. Links to related articles and cross-reading of citations in related articles were surveyed. All articles with a pertinent level of evidence were included and represent the basis for the current review article.

Evidence synthesis

In nephrectomy patients, a variety of models have been developed for prediction of recurrence and survival, both in the preoperative and postoperative settings. Several of those models relied on variables that are not routinely available in clinical practice. Not all tools were externally validated. In patients treated with systemic therapy, novel tools that were developed and validated in the targeted therapy era replaced tools devised during the cytokine era.

Conclusions

The development of ISSs for prediction of risk or prognosis in the context of RCC has evolved and improved. In the targeted therapy era, the urologic community should focus on direct comparisons of existing tools with the intent of identifying the optimal ISS for each specific end point.     

Biological characteristics of pediatric renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions

Purpose

To investigate the clinical features of pediatric Xp11.2 translocation renal cell carcinoma (RCC).

Methods

A retrospective review of 22 cases over 35 years.

Results

Xp11.2 translocation RCCs were identified in 13 boys and 9 girls with a median age of 10.5 years (range: 2.5–16 years). RCC presented with hematuria in 17, abdominal mass in 1, abdominal masses with hematuria in 2, abdominal pain with hematuria in 1, and as an incidental finding in 1 patient. Ten patients were classified stage I, 10 were stage III, and two were stage IV. Of the 10 patients with stage I RCCs, 3 patients with tumor measuring less than 7 cm had nephron-sparing surgery (NSS) and 17 patients underwent simple nephrectomy. A 15-cm tumor was incompletely removed in one patient and another patient with a 25-cm × 18-cm × 15-cm tumor had gross residual. Of the 15 patients followed up between 6 months and 35 years, 13 were still living and 2 had died after surgery.

Conclusions

Xp11.2 translocation RCC is the predominant form of pediatric RCC, associated with advanced stage at presentation. Nephrectomy is the usual treatment for RCC but NSS is an option for patients with tumors measuring < 7 cm. Patients with N + M0 maintained a favorable prognosis following surgery alone.     

Radiofrequency ablation versus partial nephrectomy in patients with solitary clinical T1a renal cell carcinoma: comparable oncologic outcomes at a minimum of 5 years of follow-up

Background

Long-term comparative outcomes for radiofrequency ablation (RFA) versus partial nephrectomy (PN) for the primary treatment of clinical T1a renal cell carcinoma (RCC) have not previously been reported.

Objective

Report comparative 5-yr oncologic outcomes for RFA versus PN in patients with clinical T1a RCC.

Design, setting, and participants

Observational single-institution cohort study, involving consecutive patients with a solitary histologically confirmed T1a RCC treated by RFA or PN and followed for a minimum of 5 yr. Those presenting with synchronous multiple, metachronous, bilateral, and/or metastatic disease, a history of hereditary RCC syndromes, a family history of RCC, and with post-treatment follow-up <5 yr were excluded from analysis.

Measurements

The Kaplan-Meier method was used to determine 5-yr overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (local RFS), overall disease-free survival (DFS), and metastasis-free survival (MFS) for RFA versus PN. Survival curves were compared using the log-rank test. A p value ≤0.05 was considered statistically significant.

Results and limitations

A total of 37 patients in each group met the selection criteria. The RFA cohort was significantly older and had more advanced comorbidities, but other patient characteristics were similar. For RFA versus PN, median follow-up was 6.5 yr (interquartile range [IQR]: 5.8–7.1) versus 6.1 yr (IQR: 5.4–7.3) (p = 0.68), respectively. The 5-yr OS was 97.2% versus 100% (p = 0.31), CSS was 97.2% versus 100% (p = 0.31), DFS was 89.2% versus 89.2% (p = 0.78), local RFS was 91.7% versus 94.6% (p = 0.96), and MFS was 97.2% versus 91.8% (p = 0.35), respectively. Study limitations are retrospective data analysis, loss to follow-up, limited statistical power, and limited generalizability of our data.

Conclusions

In appropriately selected patients, RFA is an effective minimally invasive therapy for the treatment of cT1a RCC, yielding comparable long-term oncologic outcomes to nephron-sparing surgery.     

PLIN3 is up-regulated and correlates with poor prognosis in clear cell renal cell carcinoma

Background

PLIN3, one of the members of the perilipin family, has been reported to be involved in the formation and accumulation of lipid droplets. However, the expression levels and diagnostic and prognostic value of PLIN3 in renal cell carcinoma (RCC) remain unclear.

Hypoxia and renal cell carcinoma: The influence of HIF1A+1772C/T functional genetic polymorphism on prognosis

Objectives

Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular response to hypoxia. Overexpression of HIF-1 has been implicated in the pathogenesis of renal cell carcinoma (RCC), and functional polymorphisms of the HIF1A gene may confer susceptibility to RCC. Our purpose was to assess the influence of HIF1A+1772C/T (rs11549465) polymorphism on RCC prognosis.