Comparison of Papillary Renal Cell Carcinoma Type 1 and Type 2: A Secondary Data Analysis Using the Cancer Genome Atlas

The first chapter in this manuscript serves as an overview of the background, significance, and theological framework of this study, comparison of papillary renal cell carcinoma type 1 and type 2: a secondary analysis. The body of this work focuses on the topics of the current knowledge, genetic variations and syndromes, demographics, increased risk factors, and pathways associated with type 1 and type 2 papillary renal cell carcinoma. The second chapter is a review of the literature to discuss the current working knowledge on papillary renal cell carcinoma including genetic underpinnings, disease management and histological subtyping. This chapter was designed to give clinicians a better working knowledge on papillary renal cell carcinoma. The results of this review highlight the importance of discovering discernible differences between type 1 and type 2 papillary renal cell carcinoma tumors. The third chapter is a review of the most common hereditary renal cell syndromes that are associated with an increased risk of developing renal cell carcinomas. This review covered Hereditary Leiomyomatosis and Renal Cell Cancer, a renal cancer syndrome that is characterized by benign neoplasms and is associated with an increased risk of developing type 2 papillary renal cell carcinoma. The results of this review highlighted the complex genetic nature of papillary renal cell carcinoma and provided the background for a variable used in the secondary data analysis. The fourth chapter describes the dissertation work and was a secondary data analysis on papillary renal cell carcinoma using The Cancer Genome Atlas – Cervical Kidney Renal Papillary Cell Carcinoma and cBioPortal databases. The analysis focused on determining the epidemiological, increased risk factor and pathway preference differences between type 1 and type 2 papillary renal cell carcinoma. The results of this study showed that while there are some significant differences between tumor types, further studies are warranted. The final chapter is a synthesis of all the manuscripts related to papillary renal cell carcinoma type 1 and type 2 tumors. This chapter provides a cohesive discussion of all three manuscripts and provides suggestions for future research specific to type 1 and type 2 papillary renal cell carcinoma. The result of all three manuscripts is to better provide an understanding of papillary renal cell carcinoma as a disease and to define differences between type 1 and type

A unique case of spontaneous regression of metastatic papillary renal cell carcinoma: a case report

Spontaneous regression of cancer is a rare, but well documented, phenomenon. We present a unique case of an 82 year old Chinese male who experienced spontaneous regression of histologically-verified metastatic type II papillary renal cell carcinoma in the absence of intervening systemic therapy or surgery. This is the first reported case of spontaneous regression of papillary renal cell carcinoma. The mechanism of spontaneous regression remains unknown, and represents a challenge for existing oncology paradigms

Identification of Topological Features in Renal Tumor Microenvironment Associated with Patient Survival

Motivation As a highly heterogeneous disease, the progression of tumor is not only achieved by unlimited growth of the tumor cells, but also supported, stimulated, and nurtured by the microenvironment around it. However, traditional qualitative and/or semi-quantitative parameters obtained by pathologist’s visual examination have very limited capability to capture this interaction between tumor and its microenvironment. With the advent of digital pathology, computerized image analysis may provide a better tumor characterization and give new insights into this problem. Results We propose a novel bioimage informatics pipeline for automatically characterizing the topological organization of different cell patterns in the tumor microenvironment. We apply this pipeline to the only publicly available large histopathology image dataset for a cohort of 190 patients with papillary renal cell carcinoma obtained from The Cancer Genome Atlas project. Experimental results show that the proposed topological features can successfully stratify early- and middle-stage patients with distinct survival, and show superior performance to traditional clinical features and cellular morphological and intensity features. The proposed features not only provide new insights into the topological organizations of cancers, but also can be integrated with genomic data in future studies to develop new integrative biomarkers

Renal Cell Carcinoma with Angioleiomyoma-Like Stroma and Clear Cell Papillary Renal Cell Carcinoma: Exploring SDHB Protein Immunohistochemistry and the Relationship to Tuberous Sclerosis Complex

Renal cell carcinoma (RCC) with angioleiomyoma-like stroma appears to be molecularly distinct from clear cell RCC; however, its relationship to clear cell papillary RCC remains debated. Recent studies have found that similar tumors sometimes occur in patients with tuberous sclerosis complex (TSC), of which one study found unexpectedly negative succinate dehydrogenase (SDH) B immunostaining. We evaluated immunohistochemistry for SDHB in 12 apparently sporadic RCCs with angioleiomyoma-like stroma and correlated with clinical information for stigmata of TSC. Tumors were compared to a group of 16 clear cell papillary RCCs and 6 unclassified tumors with prominent stroma. With exception of 1 unclassified tumor, all exhibited at least focal cytoplasmic staining for SDHB protein, often requiring high magnification and better appreciated with increased antibody concentration. Detailed history information was available for 9/12 patients with smooth muscle-rich tumors, revealing no stigmata of undiagnosed TSC. Electron microscopy performed on 1 of these tumors revealed mitochondria to be very sparse, potentially accounting for the weak immunohistochemical labeling for SDHB protein. Weak SDHB immunostaining may represent another shared feature of RCC with angioleiomyoma-like stroma and clear cell papillary RCC, likely due to sparse mitochondria, strengthening the possible relationship of these entities. Although smooth muscle-rich tumors have been recently reported in patients with TSC, absence of staining in tumors with this pattern may not be specific for TSC. In tumors with pale or clear cytoplasm, immunohistochemical staining for SDHB should be interpreted with caution as evidence of abnormality in the SDH pathway

Papillary Renal Cell Carcinoma: Demographics, Survival Analysis, Racial Disparities, and Genomic Landscape

Papillary renal cell carcinoma (PRCC) is the second most common histological subtype of renal cell cancer. This research aims to present a large database study highlighting the demographic, clinical, and pathological factors, racial disparities, prognosis, and survival of PRCC. The clinical and demographic data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and molecular data was cured from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. PRCC had a median age of diagnosis at 64 years, with a higher incidence in men (77%), and Whites (68%). 70.3% of cases were Grades I–IV (13, 53, 31, and 3%, respectively). In patients with known data, 85% were localized to the kidney, and 84% of cases were 7 cm in size. No metastasis occurred in 97% of the known data. The most common treatment offered was surgical resection (9%). The 5-year overall survival was 79%, with patients undergoing surgery having a 90.6% 5-year survival. Multivariable analysis revealed age > 60 years, Black race, poor histologic differentiation, distant metastases, and tumor size > 10 cm as independent risk factors for mortality. The most common mutations identified from the COSMIC database were MET, KMT2D, KMT2C, ARID1A, and SPEN. PRCC affects male individuals in the sixth decade of life. Increased age, Black race, distant metastases, and tumors > 10 cm are associated with a worse prognosis. Surgical resection offers a favorable survival outcome. Next-generation sequencing (NGS) could identify potentially targetable alterations and future personalized therapeutic approaches

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma

BACKGROUND Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. METHODS We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. RESULTS Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2'antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). CONCLUSIONS Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renalcell carcinoma consisted of at least three subtypes based on molecular and phenotypic features

Kidney: Papillary renal cell carcinoma

Review on Kidney: Papillary renal cell carcinoma, with data on clinics, and the genes involved

Hereditary papillary renal cell carcinoma

Review on Hereditary papillary renal cell carcinoma, with data on clinics, and the genes involved