Emerging Molecular Technologies in Renal Cell Carcinoma: Liquid Biopsy.

Liquid biopsy, based on the circulating tumor cells (CTCs) and cell-free nucleic acids has potential applications at multiple points throughout the natural course of cancer, from diagnosis to follow-up. The advantages of doing ctDNA assessment vs. tissue-based genomic profile are the minimal procedural risk, the possibility to serial testing in order to monitor disease-relapse and response to therapy over time and to reduce hospitalization costs during the entire process. However, some critical issues related to ctDNA assays should be taken into consideration. The sensitivity of ctDNA assays depends on the assessment technique and genetic platforms used, on tumor-organ, stage, tumor heterogeneity, tumor clonality. The specificity is usually very high, whereas the concordance with tumor-based biopsy is generally low. In patients with renal cell carcinoma (RCC), qualitative analyses of ctDNA have been performed with interesting results regarding selective pressure from therapy, therapeutic resistance, exceptional treatment response to everolimus and mutations associated with aggressive behavior. Quantitative analyses showed variations of ccfDNA levels at different tumor stage. Compared to CTC assay, ctDNA is more stable than cells and easier to isolate. Splice variants, information at single-cell level and functional assays along with proteomics, transcriptomics and metabolomics studies can be performed only in CTCs.

Adjuvant and neoadjuvant approaches for urothelial cancer: Updated indications and controversies.

Urothelial carcinoma (UC) of the bladder and upper urinary tract still results an open challenge for clinical oncologists. Excluding selected patients who will particularly benefit from chemo-radiotherapy combined to endoscopic tumour removal, surgery represents the only curative approach for localized stages. Unfortunately, over 50% of operated patients do experience local or distant recurrence of the disease. Several pre and/or postoperative treatments are under evaluation in patients with UC in order to effectively reduce the difficulty and morbidity of more extensive procedures and to increase the Disease-Free Survival (DFS). The number of trials has been rapidly increased by the development of immunocheckpoint inhibitors, used alone or in combined strategies with chemotherapy, radiotherapy or other immunotherapies. The aim of this review is to illustrate the current status of neoadjuvant and adjuvant treatments in UC focusing our attention to the major ongoing trials in these settings.

Biomarkers of aggressiveness in genitourinary tumors with emphasis on kidney, bladder, and prostate cancer.

INTRODUCTION: Over the last decade, the improvement in molecular techniques and the acquisition of genomic information has transformed and increased the quality of patient care and our knowledge of diseases. Areas covered: Protein expression levels in immunohistochemistry and molecular biomarkers are reported for their ability to predict recurrence, progression, development of metastases, or patient survival. In particular, for renal cell carcinoma, we take into consideration the biomarkers applicable to immunohistochemistry and with molecular and genetic analyses. In urothelial carcinoma, there is great interest in the possibility of distinguishing the basal vs. luminal subtypes and to acquire deeper insight into the tumor biology through examining exosomes in urine and biomarkers in the serum. In prostate cancer, single gene expression and multiple gene expression classifiers are reviewed as a tool to distinguish indolent vs. aggressive disease. Expert commentary: The genomic information along with the application of ancillary techniques allow the definition of a neoplasia not only by its morphology but also by its biological signature. This continuous increase in knowledge will result in a better comprehension of oncogenesis, development of targeted therapies and optimizing decision-making processes related to patient care.

Prostate cancer with cribriform morphology: diagnosis, aggressiveness, molecular pathology and possible relationships with intraductal carcinoma.

INTRODUCTION: The Gleason grading system is one of the most important prognostic factors in prostate cancer (PCa). From the 2005 to the 2014 conference organized by the International Society of Urological Pathology (ISUP), the histological criteria for the Gleason patterns were improved, resulting in the shrinkage of the Gleason pattern (GP) 3 and expansion of the GP 4. Areas Covered: Cribriform, fused, ill-defined and glomeruloid glands are part of the morphologic spectrum of the current GP 4. Cribriform, derived from the Latin word cribrum (i.e. sieve), was introduced by Gleason to describe glands composed of a solid sheet with perforations or lumina. Cribriform morphology has a worse prognosis compared with the other, non-cribriform, GP4 morphologies. A practical implication is that a cribriform growth precludes a patient from selecting an active surveillance (AS) protocol. Expert commentary: The presence of these four growth patterns should be incorporated into the current Grade Group (GG) system. Enhancing our understanding of cribriform tumor behavior will lead to correctly identifying and treating those patients that will die because of PCa, while sparing treatment in those who do not require it.

Contemporary grading of prostate cancer: 2017 update for pathologists and clinicians.

The Gleason grading system for prostate cancer (PCa) was developed in the 1960s by DF Gleason. Due to changes in PCa detection and treatment, the application of the Gleason grading system has changed considerably in pathology routine practice. Two consensus conferences were held in 2005 and in 2014 to update PCa Gleason grading. This review provides a summary of the changes in the grading of PCa from the original Gleason grading system to the prognostic grade grouping, as well as a discussion of the clinical significance of the percentage of Gleason patterns 4 and 5.

Pathology and molecular updates in tumors of the prostate: towards a personalized approach.

INTRODUCTION: Treatment planning in patients with prostate neoplasms and prostate cancer (PCa) is generally based on the clinical and pathological molecular markers obtained from prostate needle biopsy and/or radical prostatectomy specimens. Area covered: Pathology of prostate neoplasms is evolving rapidly. Emerging trends include new additions to the 2016 World Health Organization (WHO) tumor classification as well as expanded diagnostic utility of biomarkers and molecular testing in tissue specimens, liquid biopsies and urinary samples, with the following purposes: diagnosis, prognosis and prediction. Expert commentary: The new additions to the 2016 WHO tumor classification, which include pathological definition of Intraductal carcinoma of the prostate (IDC-P) and of a new grading system for PCa, as well as identification of molecular markers, such as TMPRSS2-ERG and AR-V7, may pave the way to personalized therapy for patients with prostate tumors.

Activity of chemokines in prostate and renal tumors and their potential role as future therapeutic targets.

Chemokines are a class of low-molecular-weight proteins that induce chemotaxis and are implicated in the modulation of angiogenesis. The imbalance among angiogenic and antiangiogenic chemokines can promote the development of several conditions, including chronic inflammation, dysplastic transformation and cancer. In this review, we describe the activity and clinical significance of chemokines in prostate and renal tumors and provide an update on ongoing studies in this setting.

Epigenetic Modifications and Modulators in Prostate Cancer.

Prostate cancer (PCa) is one of the most common malignancies in men. Its clinical behavior ranges from indolent to aggressive. The clinical and morphological methods and features currently adopted show a low predictive value concerning the definition of its level of aggressiveness. Investigations have been led to understand its complex genomic landscape to improve diagnosis and prognosis as well as to define the potential role of new therapeutic targets. Epigenetic changes, including modifications in DNA methylation and histone acetylation, can contribute to the clinical behavior of PCa. MicroRNAs (miRNAs) can be used as potential biomarkers in the definition of PCa. The reversibility of epigenetic modifications opens the door to a potential perspective in the development of epigenetics modulators. The scope of this contribution is to review the main epigenetic modifications identified in PCa, including research on epigenetic modifiers and modulators.

Long Non-coding RNAs in Prostate Cancer with Emphasis on Second Chromosome Locus Associated with Prostate-1 Expression.

Long non-coding RNAs (lncRNAs) are a class of RNA with transcripts longer than 200 nucleotides that lack functional open reading frames. They play various roles in human carcinoma, such as dysregulating gene expression in prostate cancer (PCa), which results in cancer initiation, development, and progression. The non-coding RNA SChLAP1 (second chromosome locus associated with prostate-1) is highly expressed in approximately 25% of PCas with higher prevalence in metastatic compared to localized PCa. Its expression is detectable non-invasively in PCa patient urine samples. Experimental data suggest that targeting SChLAP1 may represent a novel therapeutic application in PCa. This contribution focuses on the role of lncRNAs SChLAP1 expression in PCa diagnosis and prognosis.

Genitourinary cancers: molecular determinants for personalized therapies.

Recent insights and emerging strategies for individualized therapeutic approaches in patients with genitourinary (GU) cancers are based on patient's genomic and cancer's molecular profiles. This depends on the significant advances made in molecular biology technologies, such as next-generation sequencing and whole-exome sequencing. The rise of such novel techniques has grayly increased our knowledge on cancer cell biology and development, thus allowing to identify complex abnormalities at the genomic level. These findings have paved the way toward what is called precision medicine, thus providing healthcare from an individual perspective in patients with GU tumors.