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Context: Bladder cancer (BC) is the sixth most common malignant neoplasm in men. Recently, great effort has been devoted to the study of BC variant histology (VH). Yet, the results from these studies have shown conflicting data and remain unclear whether their presence alters recurrence and survival rates after radical cystectomy (RC). Aims: We undertook this study aiming to test the effect on VH on recurrence-free survival (RFS) and overall survival (OS) in single-center RC patients. Settings and Design: We have retrospectively analyzed medical records and pathology reports from 331 patients who underwent RC with or without pelvic lymphadenectomy at University Urology Clinic-Skopje, North Macedonia, in the period between 2010 and 2018. Subjects and Methods: Microscopic analysis of the specimens involved the evaluation of histological tumor type, tumor grade, pathological tumor node metastasis stage, presence of lymphovascular invasion, and resection margin status. Statistical Analysis Used: Univariable and multivariable Cox regression models were applied to test the effect of VH on RFS and OS. Results: We found 185 patients who matched our inclusion criteria. At multivariable analyses, lymphovascular invasion and positive resection margins were associated with shorter RFS. Similarly, patients diagnosed with lymphovascular invasion, positive resection margins, and a pelvic lymph node metastasis had poorer OS. VH was not found to be an independent predictor of both RFS and OS (P > 0.05). Conclusions: The present study did not reveal prognostic effect of VH on RFS and OS. In our series, histomorphologic parameters including lymphovascular invasion, resection margins, and pelvic lymph node metastasis were the most relevant predictors on survival outcome after RC.

Penile cancer is a rare cancer in Western countries, but is more common in parts of the developing world. Usually, it is associated with older uncircumcised men who have a long-term phymotic preputium. Here, we report a case of penile cancer in a circumcised patient, occurring 3 months after a tick bite on the head of the penis. To the best of our knowledge, this is the first report that suggests a possible association between Lyme disease and occurrence of “de novo” penile cancer. Further studies are needed to confirm this hypothesis.

The incidence of skin cancer cases and specifically melanoma has tripled since the 1990s in The Netherlands. The early detection of melanoma can lead to an almost 100% 5-year survival prognosis dropping drastically when detected later. Studies show that pathologists can have a discordance reporting of melanoma to nevi up to 14.3%. An automated method could help support pathologists in diagnosing melanoma and prioritize cases based on a risk assessment. Our method used 563 whole slide images to train and test a system comprising of two models that segment and classify skin sections to melanoma, nevus or negative for both. We used 232 slides for training and validation and the remaining 331 for testing. The first model uses a U-Net architecture to perform a semantic segmentation and the output of that model was used to feed a convolution neural network to classify the WSI with a global label. Our method achieved a Dice score of $0.835\pm 0.08$ on the segmentation of the validation set and a weighted F1-score of 0.954 on the independent test dataset. Out of the 176 melanoma slides, the algorithm managed to classify 173 correctly. Out of the 62 nevi slides the algorithm managed to correctly classify 57.

BACKGROUND: Fetal intracranial tumours are very rare. The overall incidence is 0.34 per one thousand live birth newborns. According to the new classification of central nervous system tumour (2016), a primitive neuroectodermal tumour of (PNETs) is an embryonal tumour group; these are tumours with high malignancy and belong to group IV (WHO). In our case, we will present a case of PNETs in 28 gestation week old fetus, diagnosed antenatally and confirmed postnatally.CASE REPORT: We present the third pregnancy in 29 years old patient, with two previous term deliveries of healthy newborn. She came to University clinic at 27+3 gestational week for fetal hydrocephalus. After an ultrasound and MRI scan, possibilities were explained to the parents. During the medico-ethical counselling, explain to the parents the need for operation and the possibility of postoperative adjuvant therapy, quality of life with potential future disabilities. They choose to terminate the pregnancy. Postmortem the diagnosis was PNETs. Summary of analysis: peripheral neuroectodermal tumour with ganglion and neuronal differentiationCONCLUSION: Antenatal management depends on the gestational week in the time of diagnosis and the decision of parents. If the lesion is before viability fetus, it should be offered termination of pregnancy. Another important factor is the mode of delivery, because of increased intracranial pressure although this aggressive combined modality of treatment, recurrence is often. Tree year of survival is between 53% and 73% when the adjuvant radiotherapy is included. For that, they should be diagnosed as soon as possible before achieving fetal viability. Only 18% of those tumours presenting in the first year of life are diagnosed before or at delivery.

Background: The tissue microarray (TMA), first described by Battifora and first implemented in 1998 by Kononen et al, is a powerful research tool, allowing simultaneous analysis of specimens from a large number of cases on one slide by routine slides. Unfortunately, commercial aray instruments are very expensive and thus not suitable for laboratories with limited funds. We describe simple and cost-effective method for constructing of manual TMA that can be performed by any anatomic pathology laboratory, requiring minimum skill and time. Methods: Skin punch biopsy needle of 2-mm diameter was used for extracting cores from 15 positive control breast cancer cases, 15 normal bladder tissue and 30 muscle-invasive bladder cancer and for injecting into recipient block. Result: : We constructed TMA block using skin punch biopsy needle of 2-mm, and succesfulfully performed HER 2 immunodetection and Chromogen in situ hybridization studies, without substantial tissue loss. 10% of our tumor cases exhibited Her-2 neu overexpression. An open source software programme “ТМА-Ј“ was applied to facilitate management, viewing, analysis of tissue microarray images and associated clinico-pathology data. Conclusion: : This method could be done by any pathology laboratory and represents good and reliable alternative for commercially available, expensive devices and software solutions. DOI: 10.21276/apalm.2017.1166

Detecting prostate cancer (PCa) using non-invasive diagnostic markers still remains a challenge. The aim of this study was the identification of urine proteins that are sufficiently sensitive and specific to detect PCa in the early stages. Comparative proteomics profiling of urine from patients with PCa, benign prostate hyperplasia, bladder cancer, and renal cancer, coupled with bioinformatics analysis, were performed. Statistically significant difference in abundance showed 20 and 85 proteins in the 2-D DIGE/MS and label-free LC-MS/MS experiments, respectively. In silico analysis indicated activation, binding, and cell movement of subset of immune cells as the top affected cellular functions in PCa, together with the down-regulation of Acute Phase Response Signaling and Liver X Receptor/ Retinoid X Receptor (LXR/RXR) activation pathways. The most promising biomarkers were 35, altered in PCa when compared to more than one group. Half of these have confirmed localization in normal or PCa tissues. Twenty proteins (CD14, AHSG, ENO1, ANXA1, CLU, COL6A1, C3, FGA, FGG, HPX, PTGDS, S100A9, LMAN2, ITIH4, ACTA2, GRN, HBB, PEBP1, CTSB, SPP1) are oncogenes, tumor suppressors, and multifunctional proteins with highly confirmed involvement in PCa, while 9 (AZU1, IGHG1, RNASE2, PZP, REG1A, AMY1A, AMY2A, ACTG2, COL18A1) have been associated with different cancers, but not with PCa so far, and may represent novel findings. LC-MS/MS data are available via ProteomeXchange with identifier PXD008407.

BACKGROUND The key to a more effective diagnosis, prognosis, and therapeutic management of prostate cancer (PCa) could lie in the direct analysis of cancer tissue. In this study, by comparative proteomics analysis of PCa and benign prostate hyperplasia (BPH) tissues we attempted to elucidate the proteins and regulatory pathways involved in this disease. METHODS The samples used in this study were fresh surgical tissues with clinically and histologically confirmed PCa (n = 19) and BPH (n = 33). We used two dimensional difference in gel electrophoresis (2D DIGE) coupled with mass spectrometry (MS) and bioinformatics analysis. RESULTS Thirty-nine spots with statistically significant 1.8-fold variation or more in abundance, corresponding to 28 proteins were identified. The IPA analysis pointed out to 3 possible networks regulated within MAPK, ERK, TGFB1, and ubiquitin pathways. Thirteen of the identified proteins, namely, constituents of the intermediate filaments (KRT8, KRT18, DES), potential tumor suppressors (ARHGAP1, AZGP1, GSTM2, and MFAP4), transport and membrane organization proteins (FABP5, GC, and EHD2), chaperons (FKBP4 and HSPD1) and known cancer marker (NME1) have been associated with prostate and other cancers by numerous proteomics, genomics or functional studies. We evidenced for the first time the dysregulation of 9 proteins (CSNK1A1, ARID5B, LYPLA1, PSMB6, RABEP1, TALDO1, UBE2N, PPP1CB, and SERPINB1) that may have role in PCa. The UBE2N, PSMB6, and PPP1CB, involved in cell cycle regulation and progression were evaluated by Western blot analysis which confirmed significantly higher abundances of UBE2N and PSMB6 and significantly lower abundance of PPP1CB in PCa. CONCLUSION In addition to the identification of substantial number of proteins with known association with PCa, the proteomic approach in this study revealed proteins not previously clearly related to PCa, providing a starting point for further elucidation of their function in disease initiation and progression. Prostate 75:1586–1600, 2015. © 2015 Wiley Periodicals, Inc.

Despite the overall success of prostate specific antigen (PSA) in screening and detection of prostate cancer (PCa), its use has been limited due to the lack of specificity. The principal driving goal currently within PCa research is to identify non-invasive biomarker(s) for early detection of aggressive tumors with greater sensitivity and specificity than PSA. In this study, we focused on identification of non-invasive biomarkers in urine with higher specificity than PSA. We tested urine samples from PCa and benign prostatic hyperplasia (BPH) patients by 2-D DIGE coupled with MS and bioinformatics analysis. Statistically significant (p

Proteome analysis of the urine has shown that urine contains disease-specific information for a variety of urogenital system disorders, including prostate cancer (PCa). The aim of this study was to determine the protein components of urine from PCa patients. Urine from 8 patients with clinically and histologically confirmed PCa was analyzed by conventional 2D PAGE. The MS identification of the most prominent 125 spots from the urine map revealed 45 distinct proteins. According to Gene Ontology, the identified proteins are involved in a variety of biological processes, majority of them are secreted (71%), and half of them are enzymes or transporters. Comparison with the normal urine proteome revealed 11 proteins distinctive for PCa. Using Ingenuity Pathways Analysis, we have found 3 proteins (E3 ubiquitin-protein ligase rififylin, tumor protein D52, and thymidine phosphorylase) associated with cellular growth and proliferation (p=8.35×10-4-3.41×10-2). The top network of functional associations between 11 proteins was Cell Death and Survival, Cell-To-Cell Signaling and Interaction, and System Development and Function (p=10-30). In summary, we have created an initial proteomic map of PCa patient’s urine. The results from this study provide some leads to understand the molecular bases of prostate cancer.