value of combined analysis of pro-NPY and ERG in localized prostate cancer. APMIS 2018; 126: 804-813 This study aimed to investigate if combined analysis of pro-Neuropeptide Y (NPY) and ERG expression in tumor tissue are associated with biochemical failure (BF), castration-based treatment, castration-resistant prostate cancer (CRPC), and prostate cancer (PCa)-specific death for men undergoing radical prostatectomy (RP) for PCa. This study included 315 patients, who underwent RP from 2002 to 2005. Both pro-NPY and ERG expression were analyzed using immunohistochemistry and were scored as low or high and negative or positive, respectively. Risk of BF, castrationbased treatment, CRPC, and PCa-specific death were analyzed with multiple cause-specific Cox regression analyses and stratified cumulative incidences using competing risk assessment. Median follow-up was 13.0 years (95% CI: 12.7-13.2). In total, 85.7% were pro-NPY high and 14.3% were pro-NPY low. The combined analyses of pro-NPY and ERG expression was not associated with risk of BF (p = 0.7), castration-based treatment (p = 0.8), CRPC (p = 0.4) or PCa-specific death (p = 0.5). In the multiple cause-specific Cox regression analysis, pro-NPY high and ERG positivity was not associated with BF (HR: 1.02; 95% CI 0.6-1.7; p = 0.94). In conclusion the combination of pro-NPY and ERG expression did not show association with risk of BF, castration-based treatment, CRPC, and PCa-specific death following RP.
Diagnosis of anomalous intrathoracic lesions may be challenging and require a multidisciplinary approach. We present a case of granulomatosis with polyangiitis (GPA) clinically and radiologically mimicking metastatic lung cancer with a bilateral pulmonary mass, mediastinal and cervical lymph node involvement, and pleural effusion. Surgical biopsy of the thoracic lesion revealed necrotic granulomatous inflammation, and the final diagnosis was subsequently confirmed by kidney biopsy and biochemical parameters. This case illustrates how comprehensive diagnosis secures timely and relevant treatment. Systemic vasculitis may be one of the key differential diagnoses in patients with multiorgan involvement, especially with pattern-mimicking lung cancer.
Docetaxel (DTX) was the first chemotherapeutic agent to demonstrate significant efficacy in the treatment of men with metastatic castration-resistant prostate cancer. However, response to DTX is generally short-lived, and relapse eventually occurs due to emergence of drug-resistance. We previously established two DTX-resistant prostate cancer cell lines, LNCaPR and C4-2BR, derived from the androgen‐dependent LNCaP cell line, and from the LNCaP lineage-derived androgen-independent C4-2B sub-line, respectively. Using an unbiased drug screen, we identify itraconazole (ITZ), an oral antifungal drug, as a compound that can efficiently re-sensitize drug-resistant LNCaPR and C4-2BR prostate cancer cells to DTX treatment. ITZ can re-sensitize multiple DTX-resistant cell models, not only in prostate cancer derived cells, such as PC-3 and DU145, but also in docetaxel-resistant breast cancer cells. This effect is dependent on expression of ATP-binding cassette (ABC) transporter protein ABCB1, also known as P-glycoprotein (P-gp). Molecular modeling of ITZ bound to ABCB1, indicates that ITZ binds tightly to the inward-facing form of ABCB1 thereby inhibiting the transport of DTX. Our results suggest that ITZ may provide a feasible approach to re-sensitization of DTX resistant cells, which would add to the life-prolonging effects of DTX in men with metastatic castration-resistant prostate cancer.
Aims Histopathological examination of sentinel lymph nodes in penile cancer has varied during the first 10 years after introduction of the dynamic sentinel node (SLN) procedure in Denmark, and guidelines have been sparse. The aim of this study was to investigate the impact of rigorous step‐sectioning of sentinel lymph nodes in penile cancer and improve guidelines. Methods and results Seventy‐two penile squamous cell carcinoma patients undergoing SLN procedure at a single institution in 2000–2010 were included. The archived lymph node tissues already subjected to a standard pathological examination were retrieved and the initially negative lymph nodes were subjected to an extended step‐sectioning procedure. The results were compared to clinical patient outcome from a national database and subsequent pathology reports. The original histopathological examination had detected 26 SLN with metastasis, 21 macro metastases and five micro metastases. The additional step‐sectioning procedure of this study generated 4606 slides; seven SLN metastases, two macro metastases and five micro metastases, were detected. One of the macro metastases originated from a patient in which a clinical relapse had occurred in the same groin. None of the other metastases detected in this study showed ipsilateral relapse during follow‐up. Conclusion The results underline the value of our current practice of step‐sectioning sentinel lymph nodes in penile cancer and the need for histopathological routines and guidelines. The Danish national guidelines on histopathological handling of sentinel lymph nodes have been adapted to detect any potential clinically relevant metastases.
Prostate needle biopsy cores from 249 participants in the PICTURE study (patients with a previous biopsy who underwent mpMRI followed by 5 mm transperineal mapping biopsies) were obtained. Malignant core segments (from the area with the highest Gleason score and cancer core length) as well as adjacent benign core segments were divided according to pathology on H&E and then embedded vertically into a TMA block. TMA slides were immunohistochemically stained against known prostate cancer biomarkers (PSA, PSMA, AMACR, p63, MSMB) and h-scored. Paired h-score data (i.e. from malignant and adjacent benign tissue) were compared. Visualization of h-scores against mpMRI Likert scores was also performed.RESULTS: A total of 136 pairs of malignant-benign core segments were stained. There was a statistically significant difference in hscore expression between malignant and paired benign tissue for all biomarkers, but particularly for AMACR, p63 and MSMB (Wilcoxon paired signed-rank test, p<0.001). There was no obvious correlation between IHC h-score and MRI Likert score.CONCLUSIONS: PSA, PSMA, AMACR, p63 and MSMB IHC hscores in mpMRI-characterized, malignant prostate tissue significantly differ from h-scores in surrounding benign areas, despite their proximity. This suggests a distinct expression pattern that is detectable on TMAs derived from prostate needle biopsies.
Checkpoint inhibitors have changed the treatment landscape of advanced urothelial carcinoma (mUC), and recently, a fibroblast‐growth‐factor‐receptor (FGFR) inhibitor has been introduced. This study aimed at estimating programmed death‐ligand 1 (PD‐L1) expression in primary tumors (PTs) and the PD‐L1 expression concordance between PTs and paired metastases in 100 patients with UC managed in the real‐world setting. Further, the aim was to investigate FGFR1–3 aberrations and the correlation between FGFR1–3 aberrations and PD‐L1 expression. PD‐L1 immunohistochemistry was performed on 100 formalin‐fixed paraffin‐embedded archival primary UC samples and 55 matched metastases using the 22C3 PD‐L1 assay. PD‐L1 expression was determined by the combined positive score, considered positive at ≥10. Targeted next‐generation sequencing on the S5+/Prime System with the Oncomine Comprehensive Assay version 3 was used to detect FGFR1‐3 aberrations in PTs. We found that 29 of 100 PTs had positive PD‐L1 expression. The PD‐L1 concordance rate was 71%. FGFR1‐3 aberrations were observed in 18% of PTs, most frequently FGFR3 amplifications or mutations. We found no association between FGFR1‐3 aberrations and PT PD‐L1 expression (p = 0.379). Our data emphasize the need for further studies in predictive biomarkers.
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