Publication date: February 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 2
Author(s): Lara Feulner, Hamed S. Najafabadi, Simon Tanguay, Janusz Rak, Yasser Riazalhosseini
Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.
Methods
Using The Cancer Genome Atlas (n = 436) and Cancer Genomics of the Kidney (n = 89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.
Results
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.
Conclusion
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment.
Publication date: February 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 2
Author(s): José Antonio March-Villalba, David Ramos-Soler, Pilar Soriano-Sarrió, David Hervás-Marín, Laura Martínez-García, José María Martínez-Jabaloyas
Abstract
Objectives
To investigate the expression of several immunohistochemical (IHC) markers and their predictive ability for the recurrence-free and progression-free survival of papillary urothelial bladder cancer (UBC) pTa/pT1 G2 (WHO 1973) compared to classical anatomo-clinical variables using a multidimensional analysis.
Materials and Methods
A population-based cohort of 213 primary stage UBC (pTa/pT1) G2 (WHO 1973) was evaluated by classic anatomopathological variables and characterized by immunohistochemistry (23 IHC markers, representative of different oncogenic pathways). The most important variables as a predictor of recurrence-free and progression-free survival were selected using multidimensional statistical models, such as random survival forests and least absolute shrinkage and selection operator (. Recurrence and progression-free survival of the previously selected variables were also calculated.
Results
Mean follow-up was 58 ± 33.5 months. Recurrence and progression rates were 54.5% (n = 116) and 17,4% (n = 37), respectively. The most influential variables in the low recurrence-free survival were in order: number of resected tumors, high expression of Ki67 (>10%), Cyclin D1 (>10%), and low cytoplasmic staining of p16INK4a. Regarding low progression-free survival, the most important variables were Ki67 (>15%), multicentric tumor arrangement and Survivin nuclear expression (>20%). Kaplan-Meier and cox-regression model analyses showed that the variables selected by multidimensional models were able to discriminate the clinical outcome.
Conclusions
Ki67 index is the most useful IHC marker, since it can improve the prediction of both recurrence and progression-free survival in papillary UBC pTa/pT1 G2 (WHO 1973). There are other markers, whose utility is specific to recurrence-free survival, such as Cyclin D1 and p16INK4a or in progression-free survival, such as Survivin.
Graphical Abstract
Publication date: February 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 2
Author(s): Siri Drangsholt, Dawn Walter, Shannon Ciprut, Abbey Lepor, Erica Sedlander, Caitlin Curnyn, Stacy Loeb, Patrick Malloy, Aaron N. Winn, Danil V. Makarov
Abstract
Introduction
According to current National Comprehensive Cancer Network guidelines, routine imagining for staging low-risk prostate cancer is not recommended. However, extensive overuse of guideline-discordant imaging continues to persist. Incidental findings are common on imaging and little is known about the optimal management. Rates of incidental findings vs. false positive diagnosis from inappropriate imaging are poorly understood and have yet to be quantified for low- and intermediate-risk prostate cancer patients.
Objective
To determine the frequency of positive radiologic findings in patients with low- and intermediate-risk prostate cancer during initial staging at VA New York Harbor Healthcare System.
Methods
We retrospectively reviewed all low- and intermediate-risk prostate cancer patients’ medical records from the VA New York Harbor Healthcare System for diagnosis from 2005 to 2015. We reviewed each individual's prebiopsy prostate specific antigen (PSA), Gleason score, and clinical stage. We also determined if imaging obtained yielded a false positive, incidental finding, or if metastatic disease occurred within the 6 months following initial diagnosis.
Results
There were 414 men, who were classified as low- to intermediate-risk prostate cancer and underwent inappropriate staging imaging of 4,306 men diagnosed with prostate cancer. Of these 414 men, 178 (43%) had additional follow-up imaging for positive findings. We calculated an incidental finding rate of 10% and a false positive rate of 38% for patients. Five (1%) patients had metastatic disease.
Conclusion
Despite guideline recommendations, imaging overuse remains an issue for low-intermediate-risk prostate cancer patients. The false positive rate found in this analysis is alarmingly high at 38%. This use of scans is burdensome to the healthcare system and patient. This study highlights the frequency of inappropriate imaging and its negative consequences.