Prosztata karcinóma genetikai hátterének vizsgálata = Genetic analysis of patients with prostate cancer

A prosztatarák (PCA) a fejlett országokban a férfiak második leggyakoribb daganatos haláloka. Az ösztrogén, a D vitamin receptor (VDR) és a calcium sensing receptor részben a kalcium szintre gyakorolt hatásukon keresztül befolyással bírnak a prosztata növekedésére és daganatos elfajulására. Célunk az ösztrogén (PvuII, XbaI), a D vitamin (BsmI) és a calcium sensing receptor (A986S) gének polimorfizmusának valamint a szérum kalcium szintnek a prosztata daganat kialakulására kifejtett hatásának vizsgálata volt. Felmérésünkbe 204 prosztata daganatos beteget és 102 korban illesztett kontroll egyént vontunk be. A genotípusok meghatározása után azok szérum kalcium szinttel való kapcsolatát vizsgáltuk. Mind az ösztrogén receptor alfa (ER-?) XbaI mind a VDR BsmI polimorfizmusa szignifikánsan összefüggött a prosztata daganat jelenlétével. Korban illesztett logisztikus regresszió során a magasabb korrigált szérum kalcium szint és a VDR Bb/bb genotípus egmástól függetlenül csökkentették a prosztata daganat rizikóját. Az ER-? XbaI and VDR BsmI genotípusok szignifikánsan gyakrabban fordultak elő a prosztata daganatos betecsoportban. A VDR BsmI genotípus a szérum kalcium szintre gyakorolt hatásán kívül is szignifikánsan összefüggést mutatott a prosztata daganattal, amely a VDR daganat kialakulásában betöltött közvetlen szerepére utal. | Prostate cancer (PCA) is the second leading cause of cancer death among men in developed countries. Estrogen-, vitamin D receptor (VDR), and the calcium-sensing receptor partly through their effects on calcium levels are implicated in the proliferation and carcinogenesis in the prostate gland. Our aim was to evaluate the role of estrogen (PvuII, XbaI), vitamin D (BsmI) and calcium sensing receptor (A986S) gene polymorphisms and serum calcium levels in the pathogenesis of prostate cancer. Hospital-based case-control study was performed, 204 patients with prostate cancer and 102 age-matched healthy controls were recruited in our study. After genotyping their relationship with serum calcium was investigated. Both the estrogen-alpha (ER-?) XbaI and the VDR BsmI polymorphisms significantly increased the risk of PCA. An age adjusted logistic regression showed that higher corrected serum calcium increased, and the VDR Bb/bb genotype independently decreased the risk of PCA. ER-? XbaI and VDR BsmI genetic polymorphisms had a significant association with the risk of PCA. VDR BsmI genotypes correlated with PCA independently of their effect on serum calcium suggesting a direct influence of VDR on the development of this malignancy

Paradigmaváltás a csontmetasztázisok sebészetében. I. Végtagi és medencelokalizációjú áttétek

According to the statistical data of tumor registries the incidence of cancer has increased in the last decade, however the mortality shows only a slight change due to the new and effective multimodal treatments. The aim of our overview article is to present the changes in the survival of the metastatic patients, and to demonstrate which factors influence their prognosis. The improvement of survival resulted in a more active surgical role both in metastases of the bone of the extremities and the pelvis. We present a diagnostic flow chart and current options for the reconstruction of the different regions of the bone and skeleton, and we will discuss their potential advantages, disadvantages and complications. It is evident that apart from the impending and pathological fracture surgery it is not the first choice of treatment but rather a palliative measure. The aim of surgery is to alleviate pain, to regain mobility and improve quality of life. If possible minimal invasive techniques are performed, as they are less demanding and allow fast rehabilitation for the patient, and they are solutions that last for a lifetime. In optimal conditions radical curative surgery can be performed in about 10 to 15 per cent of the cases, and better survival is encouraging. Orv Hetil. 2017; 158(40): 1563-1569

Clear cell renal cell carcinoma and papillary renal cell carcinoma: differentiation of distinct histological types with multiphase CT

PURPOSEConventional clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) have different behavioral characteristics and clinical management strategies (nephrectomy vs. nephron-sparing surgery). Our aim was to retrospectively evaluate the contrast enhancement pattern of ccRCC and pRCC and evaluate its possible diagnostic role for preoperative differentiation using a standardized protocol.MATERIALS AND METHODSQuadriphasic multidetector computed tomography (CT) images (unenhanced, corticomedullary, nephrographic, and excretory phases) of 19 patients with 20 ccRCC and 14 patients with 15 pRCC lesions (mean ages, 62.3±14.1 and 61.4±13.7 years, respectively) were reviewed retrospectively. The attenuation characteristics were compared with the attenuation of the normal renal cortex using either multiple 10 mm2 regions of interest or whole tumor attenuation measurements. The degree of contrast enhancement was also compared.RESULTSUnivariate analysis revealed that ccRCC lesions showed higher mean attenuation values on the corticomedullary and nephrographic phases compared with pRCC masses (P < 0.05) using both measurement techniques.CONCLUSIONThe findings underscore the importance of multiphase CT in the differentiation of these two subtypes of RCC using standard assessment techniques. The measurement of the degree of enhancement on contrast-enhanced multidetector CT may be a simple and useful method to radiologically differentiate between the two histological types of RCC

Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas.

OBJECTIVE Administration of targeted therapies provides a promising treatment strategy for urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC); however, the selection of appropriate drugs remains difficult. Here, we aimed to establish a routine compatible methodological pipeline for the identification of the most important therapeutic targets and potentially effective drugs for UrC and PBAC. METHODS Next-generation sequencing, using a 161 cancer driver gene panel, was performed on 41 UrC and 13 PBAC samples. Clinically relevant alterations were filtered, and therapeutic interpretation was performed by in silico evaluation of drug-gene interactions. RESULTS After data processing, 45/54 samples passed the quality control. Sequencing analysis revealed 191 pathogenic mutations in 68 genes. The most frequent gain-of-function mutations in UrC were found in KRAS (33%), and MYC (15%), while in PBAC KRAS (25%), MYC (25%), FLT3 (17%) and TERT (17%) were recurrently affected. The most frequently affected pathways were the cell cycle regulation, and the DNA damage control pathway. Actionable mutations with at least one available approved drug were identified in 31/33 (94%) UrC and 8/12 (67%) PBAC patients. CONCLUSIONS In this study, we developed a data-processing pipeline for the detection and therapeutic interpretation of genetic alterations in two rare cancers. Our analyses revealed actionable mutations in a high rate of cases, suggesting that this approach is a potentially feasible strategy for both UrC and PBAC treatments

Overexpression of CD24, c-myc and Phospholipase 2A in Prostate Cancer Tissue Samples Obtained by Needle Biopsy

Altered CD24, c-myc and phospholipase 2a expression was reported in different cancers. Our aim was to measure the expression of these genes in prostate cancer tissues, and compare it to non-cancerous samples. Prostate tissue samples were collected by needle biopsy from 20 prostate cancer (PCA) and 11 benign prostate hyperplasic (BPH) patients. RNA was isolated; cDNA synthetized, CD24, c-myc and phospholipase 2A (PL2A) expressions were determined by quantitative real-time PCR method. The expression of beta-globin gene was measured for normalization of the gene expression results. Serum prostate specific antigen (PSA) levels were determined by microparticle enzyme immunoassay (MEIA) method. PSA levels were significantly different between the PCA and BPH groups, 252.37 +/- 308.33 ng/ml vs. 3.5 +/- 2.14 ng/ml (p = 0.001), respectively. CD24 expression was 988.86 +/- 3041 ng/microl in prostate tumor and 4.00 +/- 4.25 ng/microl in the BPH group (p = 0.035). The c-myc expression was 88.32 +/- 11.93 ng/microl in the prostate tumor and 17.08 +/- 21.75 ng/microl in the BPH group (p = 0.02), and the PL2A 31.36 +/- 67.02 ng/microl was in PCA and 5.56 +/- 14.08 ng/microl in BPH (p = 0.025). Gleason's scores showed correlation with c-myc (p = 0.019) and PSA (p = 0.033) levels. Overexpression of PL2A, CD24 and c-myc was observed in prostate cancer samples using quantitative real-time PCR method

Bosniak category III cysts are more likely to be malignant than we expected in the era of multidetector computed tomography technology

Background: Complex indeterminate Bosniak category III renal cystic masses are traditionally considered to be malignant in 50%. Our aim was to retrospectively evaluate the attenuation characteristics in multiphase computed tomography (CT) and to determinate the incidence of malignancy based on histological findings on all Bosniak category III renal cystic masses investigated in our department between April 3, 2007 and November 21, 2013. Materials and Methods: Quadriphasic multidetector CT images of nineteen patients (mean age: 56.5 ± 16.5 years) with radiologically detected Bosniak category III lesions were reviewed retrospectively. All lesions were surgically removed, and the incidence of malignancy, based on pathological results was determined. Results: Calcification was present in four lesions (21%). The mean largest diameter was 48.7 ± 28.8 mm. All lesions were multilobulated and septated. Of the 19 removed lesions, 16 (84%) were malignant, and 3 (16%) were benign (one inflammatory cyst including a nephrolith, one cystic nephroma and one atypical angiomyolipoma). CT and histological findings of 19 Bosniak III cysts were correlated. Conclusion: Our study demonstrated much higher prevalence of malignancy (84%) in radiologically detected Bosniak category III cysts than it has been described before. It may due to the era of modern multidetector CT technology and multiphase protocol

Transitional cell and clear cell renal carcinoma: differentiation of distinct histological types with multiphase CT

BACKGROUND: Transitional cell carcinoma (TCC) may mimic renal cell carcinoma (RCC) when it develops in a similar location, therefore, differentiation with imaging techniques might be challenging. Preoperative differentiation may have a significant role indicating the type of surgical treatment (nephrectomy vs. ureteronephrectomy). PURPOSE: To retrospectively analyze the differences in the contrast enhancement of TCC and RCC. MATERIAL AND METHODS: Images of 20 RCC and 12 TCC (mean ages, 62.3 +/- 14.1 and 67.4 +/- 12.0 years, respectively) were analyzed from patients who underwent multiphase computed tomography (CT) examinations following 1.5 mL/kg non-ionic contrast agent administration. Unenhanced corticomedullary (30-45 s), nephrographic (70-90 s), and excretory (300-480 s) phases were imaged. The attenuation characteristics of RCC and TCC were compared to the attenuation of the normal renal cortex. RESULTS: Significant differences were found in the attenuation ratios between RCC or TCC in the corticomedullary (P = 0.040) and nephrographic (P = 0.004) phases using three regions of interest (ROIs) of 10 mm2 size. If measuring ROIs comprising the complete tumor lesion instead of three small ROIs, no significant difference was observed in the attenuation ratios between RCC in TCC in any phases. CONCLUSION: Our study reports significant attenuation differences between RCC and TCC in the corticomedullary and nephrographic phases by multiphase CT. The findings underscore the importance of multiphase CT in the differentiation of these two different entities. Using multiple small (three) ROIs is more accurate than measuring the whole tumor attenuation

MicroRNAs with Prognostic Potential for Metastasis in Clear Cell Renal Cell Carcinoma: A Comparison of Primary Tumors and Distant Metastases

Background: MicroRNAs (miRNAs) are regulators of gene expression in tumor development and progression. However, their influence on metastasis of clear cell renal cell carcinoma (ccRCC) is less understood. To determine the role of miRNAs in metastatic progression, miRNA expression in primary ccRCC was compared to distant metastases. Methods: Total RNA of 53 primary ccRCCs, 35 distant metastases from lung, bone, brain, and abdomen, as well as 17 normal kidney tissues was isolated from fresh frozen tissue and formalin-fixed paraffin-embedded (FFPE) samples. The miRNA microarrays were performed based on fresh frozen tissue. Results were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on fresh frozen tissue and FFPE samples. Real-time cell analyses and transwell invasion assays were carried out after transient transfection of microRNA-30c (miR-30c) in cell line 786-O. Results: There were 14 miRNAs differently expressed in metastatic primary ccRCC and distant metastases compared to non-metastatic primary tumors. A strong correlation of miRNAs to progression-free- and cancer-specific 5-year-survival was determined. Specific miRNAs were differently expressed in distant metastases compared to primary ccRCC. A miRNA signature distinguished lung metastases from other metastatic sites. Overexpression of miR-30c increased adherence and decreased migration and invasion in the ccRCC cell line. Conclusions: MiRNAs are deregulated in metastatic primary ccRCC and could be promising prognostic markers for an early prediction of metastasis. Alterations in miRNA expression characterize distant metastases of different metastatic sites. Furthermore, our study suggests a functional role of miR-30c in metastasis. The miRNAs could be a helpful tool for individual follow-up prediction and personalized therapy selection. © 2013 Society of Surgical Oncology