Classification Of Renal Cell Carcinoma Research Articles

Molecular Classification of Renal Cell Carcinoma and Its Implication in Future Clinical Practice.

Renal cell carcinoma (RCC) encompasses a wide spectrum of morphologically and molecularly distinct (>10) cancer subtypes originated from the kidney epithelium. Metastatic RCC (mRCC) is lethal and refractory to conventional chemotherapeutic agents. The incorporation of targeted therapies and immune checkpoint inhibitors into the current practice of mRCC has markedly improved the median overall survival of clear cell RCC (ccRCC) patients, the most common subtype, but not rare kidney cancer (RKC or non-ccRCC, nccRCC). Varied treatment response in mRCC patients is observed, which presents clinical challenges/opportunities at the modern mRCC therapeutic landscape consisting of 12 approved drugs representing 6 different effective mechanisms. Key contributing factors include inter- and intra-RCC heterogeneity. With the advances in pan-omics technologies, we now have a better understanding of the molecular pathobiology of individual RCC subtype. Here, we attempt to classify ccRCC based on contemporary molecular features with emphasis on their respective potential significance in clinical practice.

Abstract 5447: A microRNA signature for the classification of renal cell carcinoma subtypes

Abstract Introduction: Renal cell carcinoma (RCC) accounts for 90% of all kidney cancers. It comprises a heterogeneous group of renal tumors with distinct genetic and molecular characteristics including clear cell RCC (ccRCC), papillary RCC (pRCC) and chromophobe RCC (chRCC). The differential diagnosis of RCC subtypes relies on distinct morphology which is not always accurate. Accurate classification of RCC subtypes is critical since each exhibits different clinical behaviour, prognosis and response to therapy. The purpose of this study is to determine whether a limited number of miRNAs can classify RCC subtypes with high accuracy. Experimental Design: We extracted RNA from 90 formalin-fixed paraffin-embedded (FFPE) tissues including 27 clear cell RCC, 29 papillary RCC, 19 chromophobe RCC, 4 unclassified RCC tumors and 11 oncocytomas. We measured the absolute expression of six miRNAs by qRT-PCR. Receiver operator characteristic curves were constructed and the area under the curve (AUC) was calculated to assess diagnostic performance. We also tested miRNA expression by in situ hybridization (ISH) in an independent set of ninety-eight FFPE renal tumors. Results: We developed a two-step miRNA classifier. In the first step, expressions of selected miRNAs were found to discriminate clear cell RCC and papillary RCC from chromophobe RCC and renal oncocytoma. Two miRNAs were able to discriminate clear cell RCC and papillary RCC from chromophobe RCC and oncocytoma. miR-221 was significantly overexpressed in chromophobe RCC and oncocytoma compared to clear cell RCC and papillary RCC (4.49-fold change, p= 6.398e-010) and was able to discriminate between the two groups (AUC: 0.9637, 95% CI: 0.9132 to 1.014, p<0.0001). In the second step, the absolute expression of two miRNAs could distinguish clear cell RCC from papillary RCC (10.4-fold change, p = 1.243e-013). Moreover, an additional two miRNAs could differentiate chromophobe RCC from renal oncocytoma (3.30- fold change, p = 1.751e-006). In situ hybridization revealed that miRNAs display a nuclear staining pattern that was able to distinguish clear cell RCC from papillary RCC (p<0.001) and chromophobe RCC from renal oncocytoma (p =0.009). Conclusion: miRNA expressions were able to distinguish between RCC subtypes and renal oncocytoma. miRNA assessment by in situ hybridization is a clinically useful diagnostic tool that can complement current methods for RCC classification. Citation Format: Ashley Di Meo, Mereet Hanna, Rola Saleeb, Samantha Wala, Adriana Krizova, Manal Gabril, Haiyan Zhai, Maria Pasic, Andrew Evans, Fadi Brimo, George Yousef. A microRNA signature for the classification of renal cell carcinoma subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5447. doi:10.1158/1538-7445.AM2017-5447

Prognostic significance of extensive necrosis in renal cell carcinoma

Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000 and 2015. Patients' mean age was 59 years (43-77) with 16 men (76%); 12 cases (57%) were papillary RCC, 4 clear cell papillary RCC (19%), 4 clear cell RCC (19%), and 1 unclassified with sarcomatoid differentiation (5%). International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3, and 1 case was grade 4. Pathological stage was low (pT1-2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3 cm (1.2-17). In 52% (11) of cases, it was difficult to identify viable tumor, requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 cases (81%) with a mean follow-up of 59 months. Thirteen patients (62%) are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer, and 2 died due to causes unrelated to cancer. One patient (5%) with low-grade clear cell RCC developed metastases but had a contralateral RCC. In the setting of a low-grade RCC, extensive necrosis does not have an adverse prognosis. In summary, our data, together with a prior study from our institution, comprise one of the largest cohorts of extensively (>90%) necrotic RCCs and suggests that in the setting of a low-grade RCC, it portends a good prognosis (only 2/36 cases showing progression (6%) on follow-up). However, we did identify a single case of high-grade RCC with an adverse prognosis and therefore, careful attention to tumor grade and classification is critical. The presence of tumor necrosis as a prognosticator in RCCs is complex, and despite its well-accepted role as an indicator of poor prognosis, our data would suggest otherwise under specific conditions. Importantly, in diagnosing a renal mass with extensive cystic necrosis, careful and extensive sampling to identify small foci of viable tumor or "ghost" architecture may be necessary for classification. As such, evaluation of its presence should not only be quantitative, but critical attention should be made to tumor grade and stage, whereby in high-grade carcinomas, necrosis likely imparts a worse prognosis; however, in low-grade carcinomas with extensive necrosis, the histological subtype, grade, and stage drive prognosis.

Epigenetic inactivation of HOXA11, a novel functional tumor suppressor for renal cell carcinoma, is associated with RCC TNM classification.

Epigenetic inactivation of HOXA11, a putative tumor suppressor, is frequently observed in a number of solid tumors, but has not been described in RCC (renal cell carcinoma). In this study, we investigated the expression, epigenetic changes and the function of HOXA11 in human renal cell carcinoma (RCC). HOXA11 was silenced or down-regulated in RCC cell lines and tissues. Methylation specific PCR (MSP) and bisulfite genomic sequencing (BGS) revealed that the HOXA11 promoter was hypermethylated in 5/6 RCC cell lines. Demethylation treatment resulted in demethylation of the promoter and increased HOXA11 expression in these cell lines. HOXA11 methylation was also detected in 68/95 (70.5%) primary RCC tumors, but only rare adjacent non-malignant renal tissues (13%, 3/23) showed hypermethylation of promoter. We also found that the methylation of HOXA11 was associated with higher TNM classification of RCC (p<0.05). Ectopic expression of HOXA11 led to significant inhibition of proliferation, colony formation, migration and invasion abilities and induced RCC cells apoptosis. Moreover, HOXA11 was found to inhibit Wnt signaling. Thus, our study demonstrated that HOXA11 function as a tumor suppressor in RCC, while it is frequently silenced by promoter methylation in RCC.

Changing the Stage, Grade and Histological Subtypes of Renal Cell Carcinomas during 10 Years Period.

Renal cell carcinomas (RCCs) account 80-85% of all primary renal neoplasms and originate from the renal cortex. The patients who underwent radical or partial nephrectomy for renal tumour in our unit between January 2005 and 2015 were evaluated retrospectively. The patients were divided into two groups; group 1 includes patients who were treated between January 2005 and December 2009, group 2 those from January 2010 to 2015. There were 103 patients in group 1. The patients were between 21 and 89 years with mean age of 61.46 year. Renal cell carcinomas account 83.4% of the patients, benign renal tumours were 8.7% and transitional cell carcinomas were 7.7% of the patients in group 1. A total of 32.5% RCCs were classified as pT1a, 24.4% as pT1b, 15.1% as pT2a, 11.6% as pT2b, 15.1% as pT3a and 1.1% as pT4. There were 202 patients in group 2 and the patients were between 27 and 81 years with mean age of 58.5 year. Renal cell carcinomas comprised the main bulk of the tumours with 182 nephrectomy specimens. According to the pathological classification of RCCs, 51 specimens were found as pT1a, 54 were pT1b, 13 were pT2a, 14 were pT2b, 48 were pT3a and 2 were pT4. Although, the incidence of small renal masses has been increasing with widespread use of imaging techniques and recent advancements, the proportion of high grade and advanced stage renal tumours increased during the study period.

Morphologic, Molecular, and Taxonomic Evolution of Renal Cell Carcinoma: A Conceptual Perspective With Emphasis on Updates to the 2016 World Health Organization Classification.

Molecular and morphologic interrogation has driven a much-needed reexamination of renal cell carcinoma (RCC). Indeed, the recently released 2016 World Health Organization classification now recognizes 12 distinct RCC subtypes, as well as several other emerging/provisional RCC entities. From a clinical perspective, accurate RCC classification may have important implications for patients and their families, including prognostic risk stratification, targeted therapeutics selection, and identification for genetic testing. In this review, we provide a conceptual framework for approaching RCC diagnosis and classification by categorizing RCCs as tumors with clear cytoplasm, papillary architecture, and eosinophilic (oncocytic) cytoplasm. The currently recognized 2016 World Health Organization classification for RCC subtypes is briefly discussed, including new diagnostic entities (clear cell papillary RCC, hereditary leiomyomatosis and RCC-associated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, and acquired cystic disease-associated RCC) and areas of evolving RCC classification, such as transcription elongation factor B subunit 1 (TCEB1)-mutated RCC/RCC with angioleiomyoma-like stroma/RCC with leiomyomatous stroma, RCC associated with anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangement, thyroidlike follicular RCC, and RCC in neuroblastoma survivors. For each RCC subtype, relevant clinical, molecular, gross, and microscopic findings are reviewed, and ancillary studies helpful for its differential diagnosis are presented, providing a practical approach to modern RCC classification.

Recent advances in renal cell carcinoma from a pathological point of view.

The purpose of this article is to review the recent advances in renal cell carcinoma (RCC) from a pathological point of view. Because the genetic features and morphological characteristics have become major criteria for the classification of RCC, special techniques, such as immunohistochemistry, are essential to the differential diagnosis of renal tumors. Metastasis is frequently observed among the RCC patients with curative nephrectomy, and extracellular matrix-degrading enzymes, such as matrix metalloproteinases (MMP) and heparanase, play a key role in invasion and metastasis of RCC. Snail and Slug, transcription factors of epithelial-mesenchymal transition (EMT), accelerate cancer cell invasion through downregulation of E-cadherin and up-regulation of MMP. Therapies targeted at the vascular endothelial growth factor pathway have become the standard treatment of metastatic RCC. Although they lead to tumor shrinkage mainly by inhibiting angiogenesis, they have typically been associated with drug resistance. The mechanism of the resistance remains largely unknown, but complex events including re-activation of angiogenesis, EMT and cancer stem cells, and immune escape are implicated in the refractory response to the therapy. Recent advances of the research on RCC have caused the changes of classification and therapy, and pathologists should take overall view of these as integrated pathology.

Clinical evaluation of microRNA-145 expression in renal cell carcinoma: a promising molecular marker for discriminating and staging the clear cell histological subtype.

The vast majority of malignancies detected in renal parenchyma are diagnosed as renal cell carcinoma (RCC), whose subtype discrimination and determination of prognosis may contribute to the selection of the adequate therapy. Recently, a new class of small non-coding RNAs, known as microRNAs, has proven to be among the most promising biomarkers for providing this information. Herein, we sought to add up to this knowledge by evaluating the expression levels of microRNA-145 (miR-145) in RCC. For that purpose, total RNA from 58 cancerous and 44 adjacent non-cancerous renal tissues was firstly extracted and then polyadenylated and reverse transcribed to cDNA. MiR-145 levels were finally analyzed by developing and applying a highly sensitive real-time PCR protocol, while their clinical significance was determined via comprehensive statistical analysis. Our data showed that miR-145 was significantly downregulated in cancerous samples and could discriminate between clear cell and non-clear cell subtypes. Moreover, miR-145 expression was found to be correlated with primary tumor staging of cancerous samples, something also noticed in the clear cell RCC subset, in which miR-145 levels were negatively correlated with tumor size as well. Overall, these results indicate that miR-145 might constitute a promising molecular marker for RCC classification and staging.

Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH) is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD). The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB, SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene) has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

Retrospective Review of 95 Renal Cell Carcinomas Considering New Classification and Emerging Concepts

Introduction: Current classification of renal cell carcinoma (RCC) is outlined in the 2004 World Health Organization monograph. The diagnostic concepts continue advancing to keep up with the development of targeted therapies. In this study, we reviewed 95 cases diagnosed as RCC from 1998 to 2005. The study compared the new diagnoses with the original ones to determine …

Molecular pathways in renal cell carcinoma: recent advances in genetics and molecular biology.

Advanced renal cell carcinoma (RCC) remains a largely incurable disease with a grave prognosis despite the availability of a multiplicity of systemic therapies targeted against vascular endothelial growth factor, its receptors, and the mammalian target of rapamycin. Although immune 'checkpoint inhibitors' appear to have activity in clear cell RCC based on recent early phase trials, the true magnitude of the benefit conferred by these agents remains to be fully understood. Given the limitations of existing treatment paradigms, ongoing research into new targetable pathways is critical. This review will highlight some of the more promising avenues of investigation into the molecular biology of RCC. The hypoxia-inducible factor and mammalian target of rapamycin pathways remain critical targets in clear cell RCC. In addition, genes involved in chromatin remodeling such as polybromo 1 (PBRM1), SET domain containing 2 (SETD2), and BRCA-1-associated protein-1 (BAP1) have been shown to influence tumor biology and predict survival. MET alterations and the Krebs cycle enzyme fumarate hydratase are associated with familial type 1 and type 2 papillary RCC (PRCC), respectively. Alterations in nuclear factor (erythroid-derived 2)-like 2, Kelch-like erythroid-derived cap-n-collar homology-associated protein 1, and cullin 3, components of an oxidative stress response pathway, have been recently recognized in some sporadic papillary tumors as well as in fumarate hydratase-deficient tumor and may serve as additional therapeutic targets. In addition, whole-genome sequencing and integrated genomic analysis strategies are beginning to uncover unique molecular signatures associated with distinct subtypes of RCC, laying the foundation for a molecular classification of RCC and more precise, mechanism-based therapeutic intervention. The complex molecular changes underlying individual RCC variants are yet to be fully elucidated and remain the subject of ongoing investigation. The findings summarized here further exemplify the diversity of RCC and the need to tailor our therapeutic approaches to the unique genetic alterations specific to individual subtypes of RCC.

Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several independent diseases.

Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinoma (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC. We studied the clinical, histological, immunohistological, and comprehensive genetic features of a series of 31 pRCC including 15 pRCC1 and 16 pRCC2. We aimed to determine whether pRCC represents a unique entity or several diseases. In addition, we compared the genetic features of pRCC2 to those of eight RCC showing various degrees of tubulo-papillary architecture, including three TFE-translocation RCC and five unclassified RCC. We demonstrate that pRCC is a heterogeneous group of tumors with distinct evolution. While most pRCC2 had genetic profiles similar to pRCC1, some shared genomic features, such as loss of 3p and loss of chromosome 14, with clear cell RCC, TFE-translocation RCC, and unclassified RCC. We identified variants of the MET gene in three pRCC1. A mutation in the BRAF gene was also identified in one pRCC1. In addition, using next-generation sequencing (NGS), we identified several variant genes. Genomic profiling completed by NGS allowed us to classify pRCC2 in several groups and to identify novel mutations. Our findings provide novel information on the pathogenesis of pRCC that allow insights for personalized treatment.

Renal cell carcinoma: histological classification and correlation with imaging findings.

Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes.

CDK1 and CDK2 activity is a strong predictor of renal cell carcinoma recurrence

BackgroundIn renal cell carcinoma (RCC), the prediction of metastasis via tumor prognostic markers remains a major problem. The objective of our study was to evaluate the efficacy of cyclin-dependent kinase (CDK)1 and CDK2 activity as a prognostic marker in human RCC. MethodsSurgical specimens were obtained from 125 patients with RCC without metastasis. Protein expression and kinase activity of CDKs were analyzed using a newly developed assay system named C2P (Sysmex, Kobe, Japan). We then examined the specific activities (SAs) of CDK1 and CDK2 and calculated CDK2SA-CDK1SA ratio in RCC. Also, risk score (RS) was examined. ResultsA total of 125 cases were tested, though 34 cases were excluded because of low sample quality (25 cases) and assay failure (9 cases). In total, 91 cases were analyzed. They included 68 male and 23 female patients, ranging in age from 19 to 83 years. At a median follow-up of 36 months (1–109M), tumor with low CDK2SA-CDK1SA ratio showed significantly better 5-year recurrence-free survival than those with high CDK2SA-CDK1SA ratio (88.7% vs. 54.7%, P = 0.00141). Also, RS enabled the classification of RCCs into high-risk and low-risk groups, and patients with tumors classified as low RS showed better recurrence-free survival than patients with tumors with high RS (88.7% vs. 54.7%, P = 0.0141). ConclusionCDK1SA of tumors and the CDK2SA are both associated with recurrence and prognosis. ImpactCDK-based risk demonstrated is strongly associated with clinical outcome. CDK-based risk should be an accurate system for predicting recurrence and survival for planning follow-up.

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Contrast‐enhanced ultrasound characterization of renal mucinous tubular and spindle cell carcinoma: Report of two cases

Mucinous tubular and spindle cell carcinoma of the kidney is a relatively rare pathologic entity that has recently been described in the World Health Organization 2004 renal cell carcinoma classification. We report two cases of mucinous tubular and spindle cell carcinoma in which contrast-enhanced ultrasound was used.

Clear cell renal cell carcinoma with syncytial giant cells

Four types of giant cells have been reported in renal cell carcinomas: osteoclast-like giant cells, pleomorphic tumour giant cells, rhabdoid cells, and syncytial giant cells. There are apparently only four cases of renal cell carcinoma with syncytial giant cells reported in the English literature, and this type is not part of the WHO classification of renal cell carcinomas. We a report a case in a 68-year-old man. Macroscopically the tumour was a 65 mm variegated tan and haemorrhagic mass with a 50 mm necrotic central cavity, confined within the renal capsule. Microscopically the tumour was a clear cell renal cell carcinoma, Fuhrman grade 3, with rhabdoid features. There were many scattered multinucleated giant cells which had a similar immunohistochemical profile to the main mononuclear tumour cells. Staging CT showed three left sided lung nodules which will be resected.

Clear cell papillary renal cell carcinoma

Clear cell papillary renal cell carcinoma is a newly described variant of renal cell carcinoma (RCC). The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia has recently endorsed it as a distinct epithelial tumor entity and recommended the inclusion of this tumor in the ISUP Vancouver modification of the WHO 2004 histologic classification of RCCs. These tumors were originally described as a distinctive type of RCCs arising in end-stage renal disease; however, tumors with similar features can arise sporadically and have been reported in kidneys not affected by end-stage renal disease. Clear cell papillary RCCs have a distinctive morphology and immunoprofile which will be discussed in this slide seminar with case examples. Tumors with similar morphology and identical immunoprofile but also showing a characteristic smooth muscle stroma have been reported in the literature as renal angiomyodenomatous tumor (RAT). The current perspective is that both clear cell papillary RCC and RAT represent the morphologic spectrum of a single entity. Clear cell papillary RCCs lack the chromosome 3p deletion and VHL gene abnormalities, commonly seen in classic clear cell RCCs. They also lack trisomy of chromosome 7 or loss of Y chromosome, which are cytogenetic changes commonly observed in papillary RCCs. Recently clear cell papillary-like RCCs have been described in VHL patients; however these tumors lack the characteristic immunoprofile of typical clear cell papillary RCCs and frequently demonstrate chromosome 3p deletion. Clear cell papillary RCCs are typically small, biologically indolent tumors. No lymph node or distant metastasis of these tumors has been reported to date in the literature.

Development and validation of a microRNA-based diagnostic assay for classification of renal cell carcinomas

Renal cancers account for more than 3% of adult malignancies and cause more than 13,000 deaths per year in the US alone. The four most common types of kidney tumors include the malignant renal cell carcinomas; clear cell, papillary, chromophobe and the benign oncocytoma. These histological subtypes vary in their clinical course and prognosis, and different clinical strategies have been developed for their management. In some kidney tumor cases it can be very difficult for the pathologist to distinguish between tumor types on the basis of morphology and immunohistochemistry (IHC). In this publication we present the development and validation of a microRNA-based assay for classifying primary kidney tumors. The assay, which classifies the four main kidney tumor types, was developed based on the expression of a set of 24 microRNAs. A validation set of 201 independent samples was classified using the assay and analyzed blindly. The assay produced results for 92% of the samples with an accuracy of 95%.

Transition of Organizational Category on Renal Cancer

The incidence of kidney cancer is gradually increasing, with a rate of 2-3% per decade. The kidney develops various kinds of neoplasms, some of which are associated with familial cancer syndromes. Such cases have provided clues to identify the cancer-responsible genes. In 2004, the World Health Organization published a new classification system of renal neoplasms, incorporating recent knowledge obtained in the cytogenetic and molecular biological fields, i.e. genes responsible for each histologic subtype (von Hippel-Lindau for clear cell renal cell carcinoma, c-met for papillary renal cell carcinoma type 1, etc.). Subsequently, the Japanese classification system in 'the General Rule for Clinicopathological Study of Renal Cell Carcinoma' has been revised as the 4th edition, according to the World Health Organization system. Several novel subtypes have been introduced, i.e. mucinous tubular and spindle cell carcinoma, and Xp11.2/TFE3 translocation-associated renal cell carcinoma. Even after the publication of the classification, other novel subtypes have emerged, i.e. acquired cystic disease-associated renal cell carcinoma and tubulocystic renal cell carcinoma. Additionally, some of the subtypes seem to form families based on morphological transition, immunohistochemical features and gene expression profile. In future, the classification of renal cell carcinoma should be reorganized on the basis of molecular biological characteristics to establish personalized therapeutic strategies.