R. J. A. van Moorselaar

New experimental markers for early detection of high-risk prostate cancer: role of cell–cell adhesion and cell migration

Today’s treatment and diagnosis of prostate cancer still exhibit major limitations. The search for new and additional prognostic markers is therefore still an actual field of interest. Potential markers involved in numerous biological processes in the tumor cell have been investigated intensively. For therapeutic interventions it is important to distinguish between harmless and aggressive disease in an early stage. Therefore the subject of this review is limited to markers associated with those functional processes, which discriminate early stage aggressive, metastatic cancer from harmless disease. Important processes in this respect are: altered cell adhesion and cellular migration. E-cadherin, N-cadherin, β-catenin, integrins, focal adhesion kinase, connexins and matrix metalloproteinases all appear promising biological markers associated with the early stage metastatic process in prostate cancer. Here we discuss their potential to become valid biological markers based on literature data. Thus far, none of these markers proved to be a valid individual marker by itself due to prostate cancer heterogeneity and transient expression. Analyzing a combination of the potential markers discussed in this review is expected to be a better approach toward discriminating high- from low-risk tumors in an early stage of prostate cancer.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project

PurposeTo reach standardized terminology in focal therapy (FT) for prostate cancer (PCa).MethodsA four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated.ResultsConsensus was attained on 23 of 27 topics; TargetedFT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text.ConclusionFocal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Customized Tool for the Validation of Optical Coherence Tomography in Differentiation of Prostate Cancer

Objective: To design and demonstrate a customized tool to generate histologic sections of the prostate that directly correlate with needle-based optical coherence tomography pullback measurements. Materials and Methods: A customized tool was created to hold the prostatectomy specimens during optical coherence tomography measurements and formalin fixation. Using the tool, the prostate could be sliced into slices of 4 mm thickness through the optical coherence tomography measurement trajectory. In this way, whole-mount pathology slides were produced in exactly the same location as the optical coherence tomography measurements were performed. Full 3-dimensional optical coherence tomography pullbacks were fused with the histopathology slides using the 3-dimensional imaging software AMIRA, and images were compared. Results: A radical prostatectomy was performed in a patient (age: 68 years, prostate-specific antigen: 6.0 ng/mL) with Gleason score 3 + 4 = 7 in 2/5 biopsy cores on the left side (15%) and Gleason score 3 + 4 = 7 in 1/5 biopsy cores on the right side (5%). Histopathology after radical prostatectomy showed an anterior located pT2cNx adenocarcinoma (Gleason score 3 + 4 = 7). Histopathological prostate slides were produced using the customized tool for optical coherence tomography measurements, fixation, and slicing of the prostate specimens. These slides correlated exactly with the optical coherence tomography images. Various structures, for example, Gleason 3 + 4 prostate cancer, stroma, healthy glands, and cystic atrophy with septae, could be identified both on optical coherence tomography and on the histopathological prostate slides. Conclusion: We successfully designed and applied a customized tool to process radical prostatectomy specimens to improve the coregistration of whole mount histology sections to fresh tissue optical coherence tomography pullback measurements. This technique will be crucial in validating the results of optical coherence tomography imaging studies with histology and can easily be applied in other solid tissues as well, for example, lung, kidney, breast, and liver. This will help improve the efficacy of optical coherence tomography in cancer detection and staging in solid organs.

Use of animal models in diagnosis and treatment of renal cell carcinoma

SummaryThis paper gives an overview of animal models available for the study of human renal cell carcinoma. Animal model systems can be divided into four categories: drug-induced tumors, virus-induced tumors, spontaneous tumors and human tumors transplanted into nude mice. Animal models have been used for improvement of diagnostic and therapeutic procedures. New markers for the diagnosis of more aggressive tumors can, for instance, be found by comparing metastatic with non-metastatic variants of the same primary tumor. Since advanced human renal cell carcinoma is refractory to chemotherapeutic agents, most therapeutic studies on animal models are immunotherapy studies. Combination treatment of biological-response modifiers such as interferon and tumor necrosis factor, with hyperthermia, bispecific monoclonal antibodies and high-energy shock waves, show promising results. Gene therapy will open new therapeutic possibilities.

750OEARLY DETECTION OF HEREDITARY RENAL CELL CANCER BY IMPROVED EVALUATION OF SPONTANEOUS PNEUMOTHORAX PATIENTS

ABSTRACT Aim: Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant condition due to germline mutations in the folliculin (FLCN) gene, clinically characterized by skin fibrofolliculomas, lung cysts, (recurrent) spontaneous pneumothorax (SP) and an increased risk of renal cell cancer (RCC). Families with BHD are most often identified through recognition of fibrofolliculomas A less common way to identify a BHD family is through (recurrent) SP. The characteristic pulmonary cystsare generally not visible on standard chest X-ray, and therefore will be missed in the standard – according to British Thoracic Society guidelines - diagnostic work-up for SP cases. We hypothesize that supplementing the diagnostic work-up of SP patients with CT imaging will result in the identification of BHD patients presenting with SP. This provides the opportunity of the identification of (asymptomatic) RCC at an early stage by screening of identified FLCN mutation carriers. Methods: We retrospectively collected clinical and radiological data of 55 families, including 200 BHD patients with a proven pathogenic FLCN mutation. Our database started in 2004; the mean follow-up time of mutation carriers is 5 years (1-10 years). Results: Sixty patients in 33 families had (recurrent) SP. In 14 out of 30 families we detected one or more patients with RCC. In total 19 patients had a history of RCC, 7 of them had a history of (recurrent) SP and 15 patients had a positive familial history for SP. We found in 14 cases RCC at an early stage, 5 patients died due metastases. Histological diagnosis were mainly (a combination of) clear cell carcinoma and chromophobe carcinoma. Conclusions: Based on these results, we suggest that including (low dose) thoracic CT in the standard SP work up should result in the identification of BHD families. In these families annual screening for RCC should be offered to affected relatives, which was shown to result in early detection of BHD associated RCC. We show that a limited period of observation of these families has resulted in detection of 14 patients with RCC at an early stage. Disclosure: All authors have declared no conflicts of interest.