Small cell neuroendocrine prostate cancer with adenocarcinoma components-case report and literature review.

Background: Small cell neuroendocrine prostate cancer (SCNC) is a rare aggressive type of neuroendocrine prostate cancer (NEPC) characterized by aggressive clinical course and lack of response to hormone therapy. Case Description: We present a case report of a 60-year-old man diagnosed with a histologically confirmed primary metastatic (bone, lymph nodes and visceral) SCNC with small components of an adenocarcinoma with clinical symptoms mimicking an acute prostatitis. Of note, serum based neuroendocrine markers (carcinoembryonic antigen, chromogranin A) were negative and the patient had a prostate-specific antigen (PSA) elevation. Genetic testing of tumor tissue revealed breast cancer gene 2 (BRCA2) copy number loss and a retinoblastoma gene (RB1) mutation reflecting again the aggressiveness of the disease. Germline testing for the BRCA2 copy number loss was unremarkable. After 6 cycles of carboplatin and etoposide in combination with androgen deprivation therapy (ADT) the Eastern Cooperative Oncology Group (ECOG) performance status has improved from 3 to 0, in addition the patient was free of pain. In line with clinical improvement, both prostate-specific membrane antigen (PSMA) and fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) revealed a significant reduction of metastatic load. Currently, the patient is treated with ADT plus apalutamide. Conclusions: We demonstrate for the first time a case of a primary metastatic SCNC with adenocarcinoma components successfully treated by the combination of platinum-based chemotherapy plus hormonal therapy. In addition, we provide a literature overview on management of SCNC as there is no standard treatment established for this disease.

Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma.

Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value < 0.019) of CD3 intratumoral lymphocytic infiltration in PCa tissues. The analysis of IHC-based expression patterns of EMT markers showed comparable expression of all EMT markers, except vimentin, which showed higher expression in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Furthermore, gene expression analysis showed a statistically significant difference (p < 0.05) in the expression of CDH1, AR, CHEK-2, CDKN-1B, and CDC-20 and oncomiRs miR-126, miR-152-3p, miR-452, miR-145-3p, miR-196a, miR-183-3p, and miR-146b in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Overall, the survival proportion was comparable in both groups. The presence of EBV in the PCa tissues results in an increased expression of certain oncogenes, oncomiRs, and EMT marker (vimentin) and a decrease in CD3 ITL, which may be associated with the aggressive forms of PCa.

Recommendations on the treatment of metastatic hormone-sensitive prostate cancer: Patient selection.

The standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is now a combination of androgen deprivation therapy plus an androgen receptor-targeted therapy (abiraterone, apalutamide, enzalutamide or darolutamide), with or without chemotherapy (docetaxel). The selection of suitable patients for each therapeutic approach has become a determining factor to ensure efficacy and minimize side effects. This article combines recent clinical evidence with the accumulated experience of experts in medical oncology, radiation oncology and urology, to provide a comprehensive view and therapeutic recommendations for mHSPC.

Ribosome-binding protein-1 (RRBP1) expression in prostate carcinomas and its relationship with clinicopathological prognostic factors.

INTRODUCTION: Studies in recent years have shown that ribosome-binding protein-1 (RRBP1) is expressed at high rates in many cancers and that it may be a potential prognostic biomarker. The objective of the present study is to determine the RRBP1 expression level in prostatic carcinoma and neighboring non-neoplastic prostate tissue, the relationship between its expression level with prognostic factors, and the role of RRBP1 in the development of prostate cancer. MATERIALS AND METHODS: The study included 45 patients who were diagnosed with prostatic carcinoma and underwent radical prostatectomy in our center between the years 2010 and 2021. Pathology reports were reviewed. Mann-Whitney U test was used for the comparison of RRBP1 and GADPH values of the cases (control and tumoral tissue) between the primary tumor stage (pT) and Gleason score (GS) groups. Hierarchical regression analysis was used to explain the effective variables in explaining the RRBP1 value of the research cases. RESULTS: According to the Mann-Whitney U test, mean and median RRBP1-T values of the cases with GS ≥ 8 were detected to be statistically significantly higher than the mean and median RRBP1-T values of the cases with GS < 8. CONCLUSION: We found out that RRBP1 was expressed at higher rates in patients with high GS and advanced-stage patients. This result indicated that RRBP1 expression may be important in predicting the prognosis of prostate carcinoma.

Dual-mode fluorescence and colorimetric smartphone-based sensing platform with oxidation-induced self-assembled nanoflowers for sarcosine detection.

BACKGROUND: Early prostatic cancer (PCa) diagnosis significantly improves the chances of successful treatment and enhances patient survival rates. Traditional enzyme cascade-based early cancer detection methods offer efficiency and signal amplification but are limited by cost, complexity, and enzyme dependency, affecting stability and practicality. Meanwhile, sarcosine (Sar) is commonly considered a biomarker for PCa development. It is essential to develop a Sar detection method based on cascade reactions, which should be efficient, low skill requirement, and suitable for on-site testing. RESULTS: To address this, our study introduces the synthesis of organic-inorganic self-assembled nanoflowers to optimize existing detection methods. The Sar oxidase (SOX)-inorganic hybrid nanoflowers (Cu3(PO4)2:Ce@SOX) possess inherent fluorescent properties and excellent peroxidase activity, coupled with efficient enzyme loading. Based on this, we have developed a dual-mode multi-enzyme cascade nanoplatform combining fluorescence and colorimetric methods for the detection of Sar. The encapsulation yield of Cu3(PO4)2:Ce@SOX reaches 84.5 %, exhibiting a remarkable enhancement in catalytic activity by 1.26-1.29 fold compared to free SOX. The present study employing a dual-signal mechanism encompasses 'turn-off' fluorescence signals ranging from 0.5 µM to 60 µM, with a detection limit of 0.226 µM, and 'turn-on' colorimetric signals ranging from 0.18 µM to 60 µM, with a detection limit of 0.120 µM. SIGNIFICANCE: Furthermore, our study developed an intelligent smartphone sensor system utilizing cotton swabs for real-time analysis of Sar without additional instruments. The nano-platform exhibits exceptional repeatability and stability, rendering it well-suited for detecting Sar in authentic human urine samples. This innovation allows for immediate analysis, offering valuable insights for portable and efficient biosensors applicable to Sar and other analytes.

Prognostic significance of tumor suppressor protein p53 in prostate cancer.

INTRODUCTION: The p53 gene mutation is one of the most common genetic alterations in many cancers. In prostate cancer (PCa), it has been associated with a poor prognosis, tumor progression and aggressiveness. P53 mutation induces an abnormal protein expression in related tissues. AIM: This study aimed to assess p53 expression using immunohistochemistry in PCa and to discuss its prognostic value. METHODS: We have retrospectively collected all cases of PCa diagnosed in our pathology department between 2012 and 2022. An automatized immunohistochemical analysis was performed using monoclonal p53 antibody. For each case, we assessed the proportion of positive cells and the intensity of staining. P53 expression was considered abnormal when it was totally negative or overexpressed (>=50% of positive cells). RESULTS: Twenty-four cases have been selected. Abnormal p53 expression was found in 42% of cases (P53 was overexpressed in 6cases and totally negative in 4 cases). Mean age of patients with p53 abnormal expression was 70years old. Patients with p53 abnormal expression had Gleason score >7 in 5 cases, ISUP grade >2 in 3 cases, peri-neural invasion in 8cases, capsule invasion in 9cases. All patients with p53 overexpression developed androgen resistance (p<0.01). CONCLUSION: An aberrant expression profile of the p53 protein was observed in 42% of cases, and a statistically significant association was found with androgen resistance. Our results suggest a potential prognostic role of p53 in PCa.

Occupational and Environmental Exposure Influences the Inflammatory (Pro-and Anti-) Status in Benign Prostate Hyperplasia and Prostate Carcinoma Patients: A Retrospective Analysis.

Multiple diseases and disorders are connected with occupational and environmental exposure risk. It is also well-established that chemicals and chemical mixtures have an influence on the immune cells of humans. This is an important field of research that has been pursued extensively in relation to autoimmune illnesses, allergy/asthma, and lung cancer, but Prostate Carcinoma has received rare reports. Chronic chemical exposure is known to produce inflammation, which is one of the most prominent characteristics of all malignancies. Changes in the ratio of pro-inflammatory to anti-inflammatory molecules are thought to be a key factor in the emergence of inflammation. Prostate gland cells express the pro-inflammatory cytokine interleukin-18 (IL-18), which is a major facilitator of immunological responses. Conversely, interleukin-10 (IL-10) is an anti-inflammatory cytokine that is linked to immune responses and inhibits the development of an inflammatory environment. Our goal is to investigate the inflammatory status of IL-18 (pro-) and IL-10 (anti-) in a variety of occupationally exposed populations in patients with Benign Prostate Hyperplasia (BPH) and patients with Prostate Carcinoma. The present study was conducted with 664 subjects, comprising 285 Prostate Carcinoma patients, 94 BPH patients and 285 controls. The subjects of BPH and Prostate Carcinoma were screened and confirmed on the basis of Prostate Serum Antigen (PSA) and pathological biopsy. All subjects were categorized as per their occupational exposure into various groups. The pro-inflammatory and anti-inflammatory Interleukins (IL-18 and IL-10) and serum PSA levels were analysed by using corresponding quantitative ELISA kits. The results showed that as compared to control participants, the serum PSA levels were higher in the Prostate Carcinoma and BPH groups. When mean levels of IL-18 were compared between various occupational groups, Tanners (tanning industry), Agriculture, and Ordnance workers had significantly higher levels (P < 0.05) of IL-18 than sedentary workers. The pro-inflammatory cytokine (IL-18) levels were also found to be aggravated in Prostate Carcinoma compared to BPH and controls. According to the findings of the current study, the levels of inflammatory cytokines (IL-18 and IL-10) in various occupational groups of BPH, Prostate Carcinoma, and controls were altered. Long-term occupational exposure may have a negative influence on inflammation levels and the immune system; therefore, preventative measures should be explored for improved health.

Effective detection of BRAFV595E mutation in canine urothelial and prostate carcinomas using immunohistochemistry.

Canine urothelial carcinoma (UC) and prostate carcinoma (PC) frequently exhibit the BRAFV595E mutation, akin to the BRAFV600E mutation common in various human cancers. Since the initial discovery of the BRAF mutation in canine cancers in 2015, PCR has been the standard method for its detection in both liquid and tissue biopsies. Considering the similarity between the canine BRAFV595E and human BRAFV600E mutations, we hypothesized that immunohistochemistry (IHC) using a BRAFV600E-specific antibody could effectively identify the canine mutant BRAFV595E protein. We tested 122 canine UC (bladder n = 108, urethra n = 14), 21 PC, and benign tissue using IHC and performed digital droplet PCR (ddPCR) on all 122 UC and on 14 IHC positive PC cases. The results from ddPCR and IHC were concordant in 99% (135/136) of the tumours. Using IHC, BRAFV595E was detected in 72/122 (59%) UC and 14/21 (65%) PC. Staining of all benign bladder and prostate tissues was negative. If present, mutant BRAF staining was homogenous, with rare intratumour heterogeneity in three (4%) cases of UC. Additionally, the BRAFV595E mutation was more prevalent in tumours with urothelial morphology, and less common in glandular PC or UC with divergent differentiation. This study establishes that BRAFV600-specific IHC is a reliable and accurate method for detecting the mutant BRAFV595E protein in canine UC and PC. Moreover, the use of IHC, especially with tissue microarrays, provides a cost-efficient test for large-scale screening of canine cancers for the presence of BRAF mutations. This advancement paves the way for further research to define the prognostic and predictive role of this tumour marker in dogs and use IHC to stratify dogs for the treatment with BRAF inhibitors.

High-dose-rate Brachytherapy Monotherapy in Patients With Localised Prostate Cancer: Dose Modelling and Optimisation Using Computer Algorithms.

AIMS: Interstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to optimise the therapy regime variables using two models: response surface methodology (RSM) and artificial neural network (ANN). MATERIALS AND METHODS: Thirty-one studies with 5651 patients were included (2078 patients presented as low-risk, 3077 patients with intermediate-risk, and 496 patients with high-risk). A comparison of these therapy schedules was carried out using an effective biologically effective dose (BEDef) that was calculated assuming the number of treatment days and dose (D) per day. The modelling and optimization of therapy parameters (BEDef and risk level) in order to obtain the maximum biochemical free survival (BFS) were carried out by the RSM and ANN models. RESULTS: An optimal treatment schedule (BFS = 97%) for patients presented with low-risk biochemical recurrence would be D = 26 Gy applied in one application, 2 fractions at least 6 h apart, within an overall treatment time of 1 day (BEDef = 251 Gy) by the RSM and ANN model. For patients presented with intermediate- or high-risk an optimal treatment regime (BFS = 94% and 90%, respectively) would be D = 38 Gy applied in one application, 4 fractions at least 6 h apart, with an overall treatment time of 2 days (BEDef = 279 Gy) by the RSM and ANN models. CONCLUSIONS: The RSM and ANN models determine almost the same optimal values for the set of predicted therapy parameters that make a feasible selection of an optimal treatment regime.

State-of-the-art in transposable element modulation affected by drugs in malignant prostatic cancer cells.

Over recent years, the investigation of transposable elements (TEs) has granted researchers a deeper comprehension of their characteristics and functions, particularly regarding their significance in the mechanisms contributing to cancer development. This manuscript focuses on prostate carcinoma cell lines and offers a comprehensive review intended to scrutinize the associations and interactions between TEs and genes, as well as their response to treatment using various chemical drugs, emphasizing their involvement in cancer progression. We assembled a compendium of articles retrieved from the PubMed database to construct networks demonstrating correlations with genes and pharmaceuticals. In doing so, we linked the transposition of certain TE types to the expression of specific transcripts directly implicated in carcinogenesis. Additionally, we underline that treatment employing different drugs revealed unique patterns of TE reactivation. Our hypothesis gathers the current understanding and guides research toward evidence-based investigations, emphasizing the association between antiviral drugs, chemotherapy, and the reduced expression of TEs in patients affected by prostate cancer.

LC/MS/MS and GC/MS/MS metabolic profiling of Leontodon hispidulus, in vitro and in silico anticancer activity evaluation targeting hexokinase 2 enzyme.

Leontodon hispidulus Boiss is a wild annual plant growing in Egypt. The present study aims for the first time, to evaluate the phytochemical profile of the main secondary metabolites of the optimized ethanolic extract of the plant using Quadrupole Time-of-Flight Liquid chromatography-mass spectrometry and Gas chromatography-mass spectrometry. It also aims to assess the anticancer activity of its different fractions against the prostate carcinoma cell line. Moreover, an in-silico docking study was performed using the Hexokinase-two enzyme. LC-qToF-MS analysis revealed the tentative identification of 36 phenolic compounds including the glycosides of (luteolin, quercetin, kaempferol, apigenin, isorhamnetin, and daidzein), coumarines (esculin, esculetin, and daphnetin), and phenolic acids (chlorogenic, caffeic, quinic, P-coumaric, and rosmarinic). GC-MS/MS analysis revealed the presence of 18 compounds where palmitic acid, myristic acid, alpha-amyrin, and beta-amyrin were the major ones. The cytotoxic activity results revealed that methylene chloride and ethyl acetate fractions showed the highest cytotoxic activity against the PC3 cell line, with IC50 values of 19, and 19.6 µg/ml, respectively. Interestingly, the docking study demonstrated that apigenin-7-O-glucoside, luteolin-7-O-glucoside, kaempferol-3-O-glucuronide, quercetin-4'-O-glucoside, esculin, rosmarinic acid, chlorogenic acid, and α-amyrin exhibited high affinity to the selected target, HEK-2 enzyme.

Resection of Renal Cell and Prostate Carcinoma Sternum Metastases with Long-Term Follow-Up: A Report of 2 Cases.

Introduction: Rarely solitary sternum metastases are addressed by resection. Two additional cases are presented as they are interesting because of their long-term follow-up. Case Presentation: Case 1: A renal cell carcinoma was treated by transabdominal nephrectomy at age 64. Right iliac bone and sternum metastases were diagnosed 7 months later and treated by internal hemipelvectomy followed by sternum metastasectomy 6 weeks after the internal hemipelvectomy. At 12-year follow-up, the patient appears disease free. Case 2: Prostate cancer was treated by prostatectomy at age 67. A subsequent solitary sternum metastasis was resected 10 years later for persistent PSA-activity despite repeated radiotherapy. The patient remains asymptomatic for 3 years now. Conclusion: Resection of sternum metastases may have curative potential and should be considered in tumours known to be rather resistant to chemo- and/or radiotherapy.

Expression of the microtubule-associated protein 2 (MAP2) as a potential independent prognostic marker in prostate cancer.

PURPOSE: Investigation of Microtubuli-associated Protein 2 (MAP2) expression and its clinical relevance in prostate cancer. MATERIAL AND METHODS: MAP2 expression was immunohistochemically analysed on radical prostatectomy specimens using whole block sections (n = 107) and tissue microarrays (TMA; n = 310). The staining intensity was evaluated for carcinoma, benign tissue and prostatic intraepithelial neoplasia. Expression data were correlated with clinicopathological parameters and biochemical recurrence-free survival. Additionally, MAP2 protein expression was quantitatively analysed in the serum of histologically confirmed prostate carcinoma patients and the control group using a commercial enzyme-linked immunosorbent assay. RESULTS: MAP2 staining was significantly stronger in neoplastic tissue than in non-neoplastic prostatic glands, both in whole block sections (p < 0.01) and in TMA sections (p < 0.05). TMA data revealed significantly stronger MAP2 staining in high-grade tumors. Survival analysis showed a significant correlation between strong MAP2 staining in carcinoma and shortened biochemical recurrence-free survival after prostatectomy (p < 0.001). Multivariate Cox regression analysis confirmed MAP2 as an independent predictor for an unfavourable course. Mean MAP2 serum levels for non-PCA vs. PCA patients differed significantly (non-PCA = 164.7 pg/ml vs. PCA = 242.5 pg/ml, p < 0.001). CONCLUSION: The present data support MAP2 as a novel biomarker in PCA specimens. MAP2 is correlated with tumor grade and MAP2 high-expressing PCA is associated with an increased risk of biochemical recurrence after radical prostatectomy. Future studies are necessary to evaluate MAP2 as a valuable immunohistochemical biomarker in preoperative PCA diagnostic procedures, in particular with regard to treatment modalities.

A Unique Case of Prostate Carcinoma Presenting as Retroperitoneal Lymphadenopathy With Normal Levels of Prostate-Specific Antigen and a Prostate of Normal Size: A Case Report.

Despite the significant advancements in prostate-specific antigen (PSA) screening and the diverse array of available treatments, prostate cancer (PCa) still significantly contributes to cancer-related illness. The most prevalent sites for metastases are bones, distant lymph nodes, and abdominal organs. Nevertheless, metastasis to the renal and retroperitoneal regions originating from prostate cancer constitutes an exceptionally uncommon clinical occurrence. Metastatic PCa commonly presents with elevated serum PSA levels, a hallmark of its diagnostic profile. However, there are instances where patients exhibit atypical metastatic patterns or maintain normal PSA levels. In the case under consideration, the patient exhibited a periureteral tumor with an indeterminate primary origin, subsequently confirmed to be metastatic prostate cancer. This case underscores the importance of recognizing the varied and sometimes elusive presentations of metastatic PCa. Despite its rarity, the occurrence of renal and retroperitoneal metastasis emphasizes the need for vigilance and a comprehensive understanding of the diverse manifestations of advanced PCa for timely and accurate diagnosis, which is paramount in optimizing patient care and outcomes.

Metastatic PSMA avid prostate tumour with penile uptake; a rare metastatic site on PET-CT.

Prostate carcinoma is the most common malignancy in males and the second most common cause of mortality. Initially, metastatic prostate cancers tend to involve bones, but these tumours can involve any system. Gallium-68 prostate specific membrane antigen (PSMA) positron emission computed tomography (PET-CT) scan is indicated in prostate cancer patients if PSA levels are raised, and CT and bone scans are inconclusive. Metastatic penile involvement is a rare phenomenon. We present a case of prostate cancer with foci of PSMA uptake in the penile region. .

Metastatic Superscan in 18F PSMA PET/CT of a Patient with Prostate Carcinoma.

A biopsy-proven patient with prostate carcinoma aged 70 years was referred to the department of nuclear medicine for radionuclide-based therapy. His prostate-specific antigen levels were >1000 ng/mL, and prostatic magnetic resonance imaging showed an enlarged prostate with a heterogeneous signal and size 3.8x3.7x3.5 cm with few small heterogeneous nodular signals in the transition zone. He was scheduled for 18F prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scan before therapy. 18F PSMA PET/CT revealed PSMA-expressing prostate lesions (maximum standardized uptake value ~10.2) with extension into the urinary bladder along with bilateral supraclavicular, mediastinal, retrocrural, retroperitoneal, and pelvic lymph nodes and sclerotic lesions in the entire axial and appendicular skeleton.

Prostate cancer and elective nodal radiation therapy for cN0 and pN0-a never ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach.

Effect of simultaneous integrated boost concepts on photoneutron and distant out-of-field doses in VMAT for prostate cancer.

BACKGROUND: A simultaneous integrated boost (SIB) may result in increased out-of-field (DOOF) and photoneutron (HPN) doses in volumetric modulated arc therapy (VMAT) for prostate cancer (PCA). This work therefore aimed to compare DOOF and HPN in flattened (FLAT) and flattening filter-free (FFF) 6­MV and 10-MV VMAT treatment plans with and without SIB. METHODS: Eight groups of 30 VMAT plans for PCA with 6 MV or 10 MV, with or without FF and with uniform (2 Gy) or SIB target dose (2.5/3.0 Gy) prescriptions (CONV, SIB), were generated. All 240 plans were delivered on a slab-phantom and compared with respect to measured DOOF and HPN in 61.8 cm distance from the isocenter. The 6­ and 10-MV flattened VMAT plans with conventional fractionation (6- and 10-MV FLAT CONV) served as standard reference groups. Doses were analyzed as a function of delivered monitor units (MU) and weighted equivalent square field size Aeq. Pearson's correlation coefficients between the presented quantities were determined. RESULTS: The SIB plans resulted in decreased HPN over an entire prostate RT treatment course (10-MV SIB vs. CONV -38.2%). Omission of the flattening filter yielded less HPN (10-MV CONV -17.2%; 10-MV SIB -22.5%). The SIB decreased DOOF likewise by 39% for all given scenarios, while the FFF mode reduced DOOF on average by 60%. A strong Pearson correlation was found between MU and HPN (r > 0.9) as well as DOOF (0.7 < r < 0.9). CONCLUSION: For a complete treatment, SIB reduces both photoneutron and OOF doses to almost the same extent as FFF deliveries. It is recommended to apply moderately hypofractionated 6­MV SIB FFF-VMAT when considering photoneutron or OOF doses.

TRPS1 expression in primary and metastatic prostatic adenocarcinoma, muscle invasive bladder urothelial carcinoma, and breast carcinoma: Is TRPS1 truly specific and sensitive for a breast primary?

Trichorhinophalangeal syndrome type 1 (TRPS1) has been reported to be a sensitive and specific immunohistochemical (IHC) marker for breast carcinomas, especially when determining primary site of origin. However, there is limited data on TRPS1 expression in prostate and bladder cancers. A two-phase study was performed with 1) an exploratory cohort analyzing TRPS1 gene alterations in prostate, bladder, and breast carcinoma and TPRS1 mRNA expression data in prostate and bladder carcinoma; and 2) TRPS1 and GATA3 IHC in a confirmatory cohort in prostate, bladder, and breast carcinoma samples. Gene alterations were identified in a subset of breast, bladder, and prostate carcinomas and mRNA was consistently detected. In the IHC cohort, 183/210 (87.1 %) of breast, 22/69 (31.9 %) of prostate, and 20/73 (27.4 %) of urothelial carcinomas showed staining with TRPS1. Intermediate to high expression of TRPS1 was observed in 173/210 (82.8 %) of breast, 17/69 (24.6 %) of prostate, and 15/73 (20.5 %) of urothelial carcinomas. Furthermore, in prostate cancer, 26.9 % of pelvic lymph node metastases and 50 % in sites of distant metastases showed expression. Increased TRPS1 mRNA expression (p = 0.032) and IHC expression (p = 0.040) correlated with worse overall survival in bladder cancer. By comparison, GATA3 IHC stained 136/210 (64.8 %) of breast, 0/69 (0 %) of prostate, and 63/73 (93 %) of bladder carcinomas. Intermediate to high expression of GATA3 was seen in 131/210 (62.4 %) of breast and 63/73 (93 %) of bladder carcinomas. This study shows there is significant staining of TRPS1 in bladder and prostate cancers. As a result, comprehensive studies are needed to establish the true specificity of TRPS1 IHC stain across various tumor types before its widespread clinical adoption.