The pathophysiology of prostate cancer involves both genetic and acquired factors, including pathogens, such as viruses. A limited number of studies have shown the presence of Epstein-Barr virus (EBV) in prostate cancer tissues. However, there is a dearth of data exploring EBV latency profile in prostate cancer, and the relationship of EBV with histopathological features of prostate cancer. In this study, prostate cancer and benign prostatic hyperplasia (BPH) samples were screened for the presence of EBV, followed by the characterization of the EBV latency profile and analysis of histopathological parameters in EBV-positive and EBV-negative groups. A conventional PCR strategy was employed using virus-specific primers to screen EBV in 99 formalin-fixed paraffin-embedded (FFPE) prostate cancer and 33 BPH samples received for histopathological analysis during the years 2019–2020. Subsequently, cDNA samples were used in a qPCR array to analyze the expression of EBV latency-associated genes to map the latency profile EBV maintains in the samples. Finally, statistical analyses were performed to determine the correlation between EBV and several histopathological features of the samples. EBV was detected in 39% of prostate cancer and 24% of BPH samples. The histopathological analysis of prostate cancer samples identified all samples as prostatic adenocarcinoma of acinar type, while statistical analyses revealed EBV-positive samples to exhibit significantly higher (p < 0.05) Gleason major and total Gleason scores as compared to EBV-negative samples. In the EBV-positive samples, variable expression patterns of latency-associated genes were observed, where most of the samples exhibited EBV latency II/III-like profiles in prostate cancer, while latency-II-like profiles in BPH samples. This study suggests a high prevalence of EBV in prostate samples, where EBV exhibited latency II/III-like profiles. Furthermore, EBV-positive samples exhibited a higher Gleason score suggesting a possible link between EBV and the onset/progression of prostate cancers. However, future functional studies are required to understand the role of the EBV gene expression profile in the onset/progression of prostate cancer.
Introduction: Several studies have shown an association between prostate carcinoma (PCa) and certain viral infections, such as HPV, EBV, CMV, etc. Despite the evidence about the presence of the EBV in PCa tissues, it is unknown if the presence of EBV is associated with any distinct histopathological characteristics and/or survival advantages/disadvantages in patients with PCa. In this study, therefore, we analyzed the LMP-1 expression, and histopathological characteristics of EBV-positive and -negative PCa tissues, followed by the survival analysis in patients from the two groups.Material & Methods: LMP-1 expression was determined using immunohistochemistry in the EBV PCR-positive FFPE PCa samples. Subsequently, two key parameters for the characterization of PCa, i.e., Gleason scores and perineural invasion (PNI), along with intratumoral lymphocytes and stromal lymphocytic infiltration was studied in the EBV-positive and -negative PCa tissues. Lastly, the survival benefit analysis of EBV-positive and EBV-negative PCa patients was performed.Results: EBV LMP1 protein expression was found in 70.96% of EBV PCR-positive PCa tissues. Histopathological analysis showed significantly higher (p<0.05) mean major and total Gleason scores, and perineural invasion (80%) in EBV-positive as compared with the EBV-negative PCa samples. We also found a higher percentage of intratumoral and tumor-stromal lymphocytic infiltration in EBV-positive PC samples as compared to EBV-negative PCa samples. Overall, the survival proportion was similar in both EBV-positive and EBV-negative groups. However, a small difference in survival benefit emerged in the 38th month, where the mean percent survival was higher in EBV-positive PCa (41.6%) patients as compared to EBV-negative PCa patients (19.96%).Conclusion: In conclusion, the presence of EBV in the PCa tissues may lead to aggressive forms of cancer. Further studies with a larger sample size are required to strengthen the link between EBV, PCa prognosis, and survival.
The immune system plays a pivotal role in identification and clearance of tumor cells, but can also be counterproductive and enhance tumor progression. Presence of neutrophils in solid tumors, including the sixth most common cancer globally - head and neck squamous cell carcinomas (HNSCC), is associated with poor prognosis. Pro-inflammatory cytokines regulated by NF-κB promote extravasation of neutrophils into tissue; neutrophils are polarized to anti-tumor (N1) or pro-tumor (N2) phenotype through the action of various pathways, including TGF-β. The mechanism and role of neutrophil recruitment in HNSCC were explored this study. Neutrophils isolated from adult donors were co-cultured for 5 hours with conditioned media (CM) from HNSCC cells SCC-9 and Cal-27, and stained with TNF-α, ICAM-1, CCL2, CCL5 for analysis of neutrophil phenotype by flow cytometry. TGF-β blocking antibody was used to explore the role of TGF-β in polarization of neutrophils. Canonical and non-canonical TGF-β signaling pathway activation was also investigated in these neutrophils through western blots. Using HNSCC patient samples, qPCR was performed for expression of genes involved in apoptosis, epithelial-to-mesenchymal transition, metastasis, and neutrophil function. Following co-culture with 24-hour HNSCC CM, neutrophils begin to exhibit cell surface markers indicative of N2 phenotype, which is impacted by TGF-β blocking antibody. Neutrophils co-cultured with HNSCC CM exhibited altered expression of TGF-β mediators Smad2/3, p38 and Akt, which was abrogated with the addition of TGF-β blocking antibody indicating specificity of a TGF-β induced signaling. Gene expression analysis exhibited significantly higher expression of anti-apoptotic BCL2 and neutrophil function marker alpha defensin 1 in HNSCC patient samples with greater neutrophil infiltration, while caspase 3 was expressed at significantly higher levels in HNSCC patient samples with low neutrophil infiltration. HNSCC cells recruit neutrophils; evidence suggests that TGF-β pathway, which typically promotes N2 phenotype in neutrophils, is involved via canonical and non-canonical mediators including p38 and Akt. Further, HNSCC patient samples have varying levels of neutrophil infiltration and differentially express genes involved in apoptosis, EMT, metastasis and invasion, inflammation. Citation Format: Kulsoom Ghias, Hina Shakeel, Alisalman Sheikh, Syed Hani Abidi, Kiran I. Masood, Saira Fatima, Fareena Bilwani. Mechanism and role of neutrophil recruitment in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5942.
Introduction: The pathophysiology of prostate cancer involves both genetic and acquired factors, including pathogens, such as viruses. A limited number of studies have shown the presence of Epstein-Barr virus (EBV) in prostate cancer tissues. However, there is a dearth of data exploring EBV latency profile in prostate cancer, and the relationship of EBV with histopathological features of prostate cancer. In this study, prostate cancer and benign prostatic hyperplasia (BPH) samples were screened for the presence of EBV, followed by the characterization of the EBV latency profile and analysis of histopathological parameters in EBV-positive and EBV-negative groups. Material & Methods: A conventional PCR strategy was employed using virus-specific primers to screen EBV in 99 formalin-fixed paraffin-embedded (FFPE) prostate cancer and 33 BPH samples received for histopathological analysis during the years 2019-2020. Subsequently, cDNA samples were used in a qPCR array to analyze the expression of EBV latency-associated genes to map the latency profile EBV maintains in the samples. Finally, statistical analyses were performed to determine the correlation between EBV and several histopathological features of the samples. Results: EBV was detected in 39% of prostate cancer and 24% of BPH samples. The histopathological analysis of prostate cancer samples identified all samples as prostatic adenocarcinoma of acinar type, while statistical analyses revealed EBV-positive samples to exhibit significantly higher (p<0.05) Gleason major and total Gleason scores as compared to EBV-negative samples. In the EBV positive samples, variable expression patterns of latency-associated genes were observed, where most of the samples exhibited EBV latency II/III-like profiles in prostate cancer, while latency-II-like profiles in BPH samples.Conclusion: This study suggests a high prevalence of EBV in prostate samples, where EBV exhibited latency II/III-like profiles. Furthermore, EBV-positive samples exhibited a higher Gleason score suggesting a possible link between EBV and onset/progression of prostate cancers. However, future functional studies are required to understand the role of the EBV gene expression profile in the onset/progression of prostate cancer.
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