Abstract:A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTA single primary growth pattern was observed in 28 cases, a secondary pattern in 11 cases and a tertiary pattern in 6 cases. Cribriform, solid and small acinar/ductal were the most common primary, secondary and tertiary morphological patterns, respectively.The highest Gleason score (GS10) was obtained in 46.7% of cases. Nine of 14 metastasizing cases were classified as GS10. Gleason pattern 5 was present in 33 of cases.This study suggests that the modified… Show more
“…As such, cytology can be considered a reasonable non‐invasive diagnostic tool in light of suspicious imaging and clinical findings and can be followed by histopathology for confirmation diagnosis if the results are equivocal. Additionally, at present, it is difficult to establish the prognostic significance of different subtypes of canine PCs, though a canine Gleason score has recently been proposed . Similarly in human medicine, histopathology is able to identify high‐grade prostate intra‐epithelial neoplasm (HG‐PIN) and atypical small acinar proliferation as premalignant histopathologic lesions that raise concern for development of prostate cancer .…”
Section: Discussionmentioning
confidence: 99%
“…However, in a recent study 32 canine Gleason score has recently been proposed. 36 Similarly in human medicine, histopathology is able to identify high-grade prostate intra-epithelial neoplasm (HG-PIN) and atypical small acinar proliferation as premalignant histopathologic lesions that raise concern for development of prostate cancer. 37 A study on HG-PIN in dogs suggested that early events in the carcinogenesis of the prostate may occur similarly in the prostate of elderly, sexually intact dogs; 38 another study conducted on military dogs found that HG-PIN was present in 18 of 25 dogs (72%) with PC.…”
Literature describing medical treatment of canine prostatic carcinoma (PC) is sparse. The aims of this study were to assess outcomes, including time to progression (TTP) and median survival time (MST), of canine PC treated with non-steroidal anti-inflammatory drugs (NSAIDs) and/or chemotherapy, and to identify prognostic factors. Records from 8 institutions were searched for dogs with cytologically or histologically confirmed PC without bladder involvement: 67 dogs were included. Presenting signs were urinary (25), gastrointestinal ([GI], 11) and systemic (3); 16 dogs had GI and urinary signs, 7 dogs had systemic signs with concurrent GI or urinary signs and in 5 dogs the tumour was an incidental finding. Out of 27 dogs, 9 (33%) had positive urine culture. Metastases were identified in 26 dogs to lymph nodes (19), lungs (10), bone (2) and liver (1). Treatment included NSAIDs and chemotherapy (32), NSAIDs alone (31) and chemotherapy alone (4). The overall MST was 82 days (range 9-752) and median TTP was 63 days (range 9-752). Dogs receiving NSAIDs combined with chemotherapy experienced a significantly longer MST (106 vs 51 days; P = .035) and TTP (76 vs 44 days; P = .02) compared to dogs receiving NSAIDs alone. Intact dogs and those with metastatic disease had significantly shorter MST (31 vs 90 days, P = .018 and 49 vs 109 days, P = .037, respectively); intact dogs also had significantly shorter TTP (25 vs 63 days, P = .0003). This study suggests that a combination of NSAIDs and chemotherapy may improve outcomes in canine PC. Metastatic disease and being entire negatively influenced prognosis.
“…As such, cytology can be considered a reasonable non‐invasive diagnostic tool in light of suspicious imaging and clinical findings and can be followed by histopathology for confirmation diagnosis if the results are equivocal. Additionally, at present, it is difficult to establish the prognostic significance of different subtypes of canine PCs, though a canine Gleason score has recently been proposed . Similarly in human medicine, histopathology is able to identify high‐grade prostate intra‐epithelial neoplasm (HG‐PIN) and atypical small acinar proliferation as premalignant histopathologic lesions that raise concern for development of prostate cancer .…”
Section: Discussionmentioning
confidence: 99%
“…However, in a recent study 32 canine Gleason score has recently been proposed. 36 Similarly in human medicine, histopathology is able to identify high-grade prostate intra-epithelial neoplasm (HG-PIN) and atypical small acinar proliferation as premalignant histopathologic lesions that raise concern for development of prostate cancer. 37 A study on HG-PIN in dogs suggested that early events in the carcinogenesis of the prostate may occur similarly in the prostate of elderly, sexually intact dogs; 38 another study conducted on military dogs found that HG-PIN was present in 18 of 25 dogs (72%) with PC.…”
Literature describing medical treatment of canine prostatic carcinoma (PC) is sparse. The aims of this study were to assess outcomes, including time to progression (TTP) and median survival time (MST), of canine PC treated with non-steroidal anti-inflammatory drugs (NSAIDs) and/or chemotherapy, and to identify prognostic factors. Records from 8 institutions were searched for dogs with cytologically or histologically confirmed PC without bladder involvement: 67 dogs were included. Presenting signs were urinary (25), gastrointestinal ([GI], 11) and systemic (3); 16 dogs had GI and urinary signs, 7 dogs had systemic signs with concurrent GI or urinary signs and in 5 dogs the tumour was an incidental finding. Out of 27 dogs, 9 (33%) had positive urine culture. Metastases were identified in 26 dogs to lymph nodes (19), lungs (10), bone (2) and liver (1). Treatment included NSAIDs and chemotherapy (32), NSAIDs alone (31) and chemotherapy alone (4). The overall MST was 82 days (range 9-752) and median TTP was 63 days (range 9-752). Dogs receiving NSAIDs combined with chemotherapy experienced a significantly longer MST (106 vs 51 days; P = .035) and TTP (76 vs 44 days; P = .02) compared to dogs receiving NSAIDs alone. Intact dogs and those with metastatic disease had significantly shorter MST (31 vs 90 days, P = .018 and 49 vs 109 days, P = .037, respectively); intact dogs also had significantly shorter TTP (25 vs 63 days, P = .0003). This study suggests that a combination of NSAIDs and chemotherapy may improve outcomes in canine PC. Metastatic disease and being entire negatively influenced prognosis.
“…Dementsprechend steht in der Veterinärmedizin oft nur ein kleiner Teil des Tumors zur histologischen Untersuchung zur Verfügung. Dies limitiert die histologische Diagnose stark, da in nicht beprobten Anteilen der Neoplasie möglicherweise andere histologische Wachstumsmuster vorhanden sind [28].…”
Section: Diskussionunclassified
“…▶Tab. 2 Nachweis der BRAF-Mutation in Prostatakarzinomen (n = 35) in Abhängigkeit vom vorherrschenden histologischen Wachstumsmuster nach Palmieri und Grieco [28].▶Table 2 Detection of BRAF mutation in prostate carcinomas (n = 35) depending on the predominant histological growth pattern according to Palmieri and Grieco[28]. Signalement der Rüden mit verschiedenen Prostataerkrankungen, deren Proben auf das Vorliegen der BRAF-Mutation untersucht wurden.…”
unclassified
“…Nachweis der BRAF-Mutation und Anzahl unterschiedlicher Wachstumsmuster nach Palmieri und Grieco[28] bei Prostatakarzinomen (n = 35).▶Table Detection of BRAF mutation and number of different growth pattern according to Palmieri und Grieco[28] in prostate carcinomas (n = 35). Unterschiedliche zytologische Befunde in Präparaten von Feinnadelaspiraten.…”
Zusammenfassung
Gegenstand und Ziel In der Literatur konnte in 80 % der Bioptate kaniner Prostatakarzinome (PCa) die BRAF-Mutation nachgewiesen werden. Ziele dieser Arbeit waren, kanine Prostataproben aus dem eigenen Tiergut hinsichtlich des Auftretens der BRAF-Mutation zu untersuchen sowie die Spezifität und Sensitivität des Tests zu evaluieren. Außerdem sollte die Methodik für zytologische Ausstriche etabliert und die Korrelation zwischen der BRAF-Mutation und dem histologischen Bild kaniner PCa dargestellt werden.
Material und Methoden Bioptate (n = 70) und Feinnadelaspirate (n = 17) der Prostata von 87 Hunden wurden histologisch oder zytologisch untersucht. Die Einteilung der Erkrankungen erfolgte wie in der Literatur beschrieben in benigne Prostatahyperplasie (BPH, n = 22), Prostatitis (n = 14), Plattenepithelmetaplasie (PM, n = 2), Atrophie nach Kastration (n = 3) und PCa (n = 46; davon zytologisch nachgewiesen n = 11). Für die PCa wurde der Gleason-Score ermittelt. Zur DNA-Isolierung dienten kommerzielle Testkits. Das Exon 15 wurde mit dem TaqMan® SNP Assay untersucht. Die Spezifität und Sensitivität des Tests wurden berechnet.
Ergebnisse Ein Gleason-Score von 6 und 7 ergab sich in je einem Fall, von 8 bis 10 bei 33 der PCa. Aus allen Proben ließ sich ausreichend DNA isolieren. Die BRAF-Mutation war in 28/46 PCa nachweisbar (Sensitivität 61 %). Bei keinem Hund mit BPH, Prostatitis, PM oder Atrophie wurde die BRAF-Mutation festgestellt (Spezifität 100 %). Durch die BRAF-Mutation verursachte PCa wiesen einen signifikant (p = 0,002) höheren Gleason-Score auf als PCa ohne diese Mutation.
Schlussfolgerung und klinische Relevanz Die Untersuchung auf das Vorliegen der BRAF-Variante V595E ist ein hochspezifisches Verfahren, mit dem sich in histologisch und zytologisch fraglichen Fällen die Verdachtsdiagnose eines PCa absichern lässt. Durch die BRAF-Mutation verursachte PCa zeigen histologisch stärker ausgeprägte Malignitätskriterien als nicht durch diese Mutation bedingte. Die klinische, therapeutische und prognostische Relevanz dieser Befunde bedarf weiterer Studien.
Background
Vascular endothelial growth factor‐A (VEGF‐A) and its receptor, VEGF receptor‐2 (VEGFR‐2), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF‐A/VEGFR‐2 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF‐A and VEGFR‐2 in canine prostate cancer (PC).
Methods
We analyzed VEGF‐A and VEGFR‐2 expression in 87 PC samples by immunohistochemistry and quantitative‐polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF‐A and VEGFR‐2 was quantified using a selected threshold from the ImageJ Software. Microvascular density was assessed by cluster of differentiation 31 staining and counting the number of positive vessels. Additionally, the homology of VEGF‐A and VEGFR‐2 between humans and dogs was assessed, followed by the construction of a protein structure homology model to compare the tertiary structures of these proteins in both species.
Results
Negative to weakly positive expression levels of VEGF‐A and VEGFR‐2 were observed in the epithelial cells of the normal prostate (NP) and prostatic hyperplasia samples. In contrast, the canine proliferative atrophy and PC samples exhibited higher VEGF‐A (p < .0001) and VEGFR‐2 (p < .0001) compared to NP. Moreover, positive correlations between the expression levels of VEGF‐A and VEGFR‐2 (Spearman's coefficient (r) = .68, p = .013) and the expression levels of VEGF‐A and VEGFR‐2 proteins (r = .8, p < .0001) were also observed in the NP samples. Additionally, the patients with PC exhibiting higher VEGFR‐2 expression levels experienced a shorter survival period (p = .0372). Furthermore, we found an association between the microvascular density and overall survival. Dogs with a higher number of vessels showed a shorter survival time. We further demonstrated that the VEGF‐A and VEGFR‐2 exhibited high homology between humans and dogs, and identified their protein structures in both species.
Conclusions
In conclusion, VEGFR‐2 appears to be an independent prognostic factor in animals with PC. VEGF‐A and VEGFR‐2 are highly conserved between humans and dogs, which can be investigated further in future cross‐species studies to explore their therapeutic applications.
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