Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

Abdelhady, Ahmed M.; El-Hindawi, Ali; Hammam, Olfat; Khalil, Heba; Diab, Sara; El-Aziz, Soulafa Abd; Badawy, Mohamed; Ismail, A.; Helmy, Nivine A.; Kamel, Nora N.; Anis, Shady E.; Kholy, Amr El; Osili, Khalid Al; Abdel-Hady, Afaf Ahmed; Nour, Hani H.; Akl, Maha

doi:10.3889/oamjms.2017.037

Cited by 8 publications

(5 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The overexpression of ERG is a biomarker of fusion, and may be related to unfavorable prognostic factors and decreased survival ( 80 – 83 ). The incidence of fusion significantly differs between the nationalities and our results were similar to other Polish data ( 26 , 84 , 85 ). We performed the immunohistochemical evaluation of ERG status and its associations with clinico-pathological variables and neural parameters finding that ND PGP 9.5 was significantly higher in ERG-positive cancers compared to ERG-negative ones.…”

Section: Discussionsupporting

confidence: 91%

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

et al. 2021

View full text Add to dashboard Cite

BackgroundCancer stroma contains the neural compartment with specific components and action. Neural microenvironment processing includes among others axonogenesis, perineural invasion (PNI), neurosignaling, and tumor cell neural/neuroendocrine differentiation. Growing data suggest that tumor-neural crosstalk plays an important function in prostate cancer (PCa) biology. However, the mechanisms involved in PNI and axonogenesis, as well as their patho-clinical correlations in this tumor are unclear.MethodsThe present study was carried out on FFPE samples of 73 PCa and 15 benign prostate (BP) cases. Immunohistochemistry with neural markers PGP9.5, TH, and NFP was performed on constructed TMAs and selected tissue sections. The analyzed parameters of tumor innervation included small nerve density (ND) measured on pan-neural marker (PGP9.5) and TH s4tained slides, as well assessment of PNI presence and morphology. The qualitative and topographic aspects were studied. In addition, the expression of neuroendocrine marker chromogranin and NPY was assessed with dedicated indexes. The correlations of the above parameters with basic patho-clinical data such as patients’ age, tumor stage, grade, angioinvasion, and ERG status were examined.ResultsThe study showed that innervation parameters differed between cancer and BP. The neural network in PCa revealed heterogeneity, and ND PGP9.5 in tumor was significantly lower than in its periphery. The density of sympathetic TH-positive fibers and its proportion to all fibers was lower in cancer than in the periphery and BP samples. Perineural invasion was confirmed in 76% of cases, usually multifocally, occurring more commonly in tumors with a higher grade. NPY expression in PCa cells was common with its intensity often rising towards PNI. ERG+ tumors showed higher ND, more frequent PNI, and a higher stage. Moreover, chromogranin-positive cells were more pronounced in PCa with higher NPY expression.ConclusionsThe analysis showed an irregular axonal network in prostate cancer with higher neural density (panneural and adrenergic) in the surroundings and the invasive front. ND and PNI interrelated with NPY expression, neuroendocrine differentiation, and ERG status. The above findings support new evidence for the presence of autocrine and paracrine interactions in prostate cancer neural microenvironment.

show abstract

Section: Discussionsupporting

confidence: 91%

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The most commonly reported genomic alteration that drives prostate tumorigenesis is TMRPSS2-ERG fusion, and this androgen-upregulating fusion is known to correlate with higher grades of the disease. Although men of African ancestry are known to present with higher disease grade, only three studies have examined the TMRPSS2-ERG fusion on the Continent ( 187 – 189 ). This fusion often results from either a chromosomal translocation or an interstitial deletion, and these studies reported rates that were less than 20% in Ghanaian and Black South African patients ( 187 – 189 ).…”

Section: Resultsmentioning

confidence: 99%

A Review of Cancer Genetics and Genomics Studies in Africa

Rotimi

Salhia

2021

Front. Oncol.

View full text Add to dashboard Cite

Cancer is the second leading cause of death globally and is projected to overtake infectious disease as the leading cause of mortality in Africa within the next two decades. Cancer is a group of genomic diseases that presents with intra- and inter-population unique phenotypes, with Black populations having the burden of morbidity and mortality for most types. At large, the prevention and treatment of cancers have been propelled by the understanding of the genetic make-up of the disease of mostly non-African populations. By the same token, there is a wide knowledge gap in understanding the underlying genetic causes of, and genomic alterations associated with, cancer among black Africans. Accordingly, we performed a review of the literature to survey existing studies on cancer genetics/genomics and curated findings pertaining to publications across multiple cancer types conducted on African populations. We used PubMed MeSH terms to retrieve the relevant publications from 1990 to December 2019. The metadata of these publications were extracted using R text mining packages: RISmed and Pubmed.mineR. The data showed that only 0.329% of cancer publications globally were on Africa, and only 0.016% were on cancer genetics/genomics from Africa. Although the most prevalent cancers in Africa are cancers of the breast, cervix, uterus, and prostate, publications representing breast, colorectal, liver, and blood cancers were the most frequent in our review. The most frequently reported cancer genes were BRCA1, BRCA2, and TP53. Next, the genes reported in the reviewed publications’ abstracts were extracted and annotated into three gene ontology classes. Genes in the cellular component class were mostly associated with cell part and organelle part, while those in biological process and molecular function classes were mainly associated with cell process, biological regulation, and binding, and catalytic activity, respectively. Overall, this review highlights the paucity of research on cancer genomics on African populations, identified gaps, and discussed the need for concerted efforts to encourage more research on cancer genomics in Africa.

show abstract

“…Gene rearrangements lead to increased activity of the ETS system, which enhances cancer growth and development. In turn, fusion between TMPRSS2 and ERG, which show functional similarity to ETS gene fusions, is present in around 50% of PCa cases and regulates key PCa biological functions [ 43 – 45 ].…”

Section: Role Of Parp In Prostate Cancer (Pca) Biologymentioning

confidence: 99%

Poly(ADP-Ribose) Polymerase Inhibitors in Prostate Cancer: Molecular Mechanisms, and Preclinical and Clinical Data

2020

View full text Add to dashboard Cite

Genomic instability is one of the hallmarks of cancer. The incidence of genetic alterations in homologous recombination repair genes increases during cancer progression, and 20% of prostate cancers (PCas) have defects in DNA repair genes. Several somatic and germline gene alterations drive prostate cancer tumorigenesis, and the most important of these are BRCA2, BRCA1, ATM and CHEK2. There is a group of BRCAness tumours that share phenotypic and genotypic properties with classical BRCA-mutated tumours. Poly(ADP-ribose) polymerase inhibitors (PARPis) show synthetic lethality in cancer cells with impaired homologous recombination genes, and patients with these alterations are candidates for PARPi therapy. Androgen deprivation therapy is the mainstay of PCa therapy. PARPis decrease androgen signalling by interaction with molecular mechanisms of the androgen nuclear complex. The PROFOUND phase III trial, comparing olaparib with enzalutamide/abiraterone therapy, revealed increased radiological progression-free survival (rPFS) and overall survival (OS) among patients with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1, BRCA2 or ATM mutations. The clinical efficacy of PARPis has been confirmed in ovarian, breast, pancreatic and recently also in a subset of PCa. There is growing evidence that molecular tumour boards are the future of the oncological therapeutic approach in prostate cancer. In this review, we summarise the data concerning the molecular mechanisms and preclinical and clinical data of PARPis in PCa. Key Points Molecular tumour profiling is a new approach for personalised targeted therapy in cancer patients.

show abstract

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

Cited by 8 publications

References 53 publications

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

A Review of Cancer Genetics and Genomics Studies in Africa

Poly(ADP-Ribose) Polymerase Inhibitors in Prostate Cancer: Molecular Mechanisms, and Preclinical and Clinical Data

Contact Info

Product

Resources

About