https://www.sciencedirect.com/science/article/abs/pii/S1092913421000290
Trabalhos de Pesquisa realizado na Universidade Federal do Ceará
Introduction
Prostate cancer is the second-most common tumor among men worldwide [1]. Most prostatic carcinomas are latent, with no impact on the patient’s life [2], but with the advent of accessible diagnostic tools indolent early-stage tumors are being overdiagnosed [3], resulting in the administration of excessively aggressive treatments to low-risk patients and, consequently, an increased risk of adverse effects such as urinary incontinence, erectile dysfunction and intestinal disturbances [4,5].
Histological analysis of biopsied tissue is essential to confirm the diagnosis of cancer and to assign the tumor a Gleason score. The latter is strongly associated with prognosis and is probably one of the best predictors of disease progression. However, the reliability of Gleason grading may be compromised by differences in grading between biopsy and prostatectomy specimens associated with tumor heterogeneity (sampling variation) [6,7] and inter-examiner disagreement [6,8,9].
Shipitsin et al. [10] looked at 160 proteins with a potential for use as biomarkers of prostate cancer (very low, low and high risk), narrowing the list down to 12 promising markers, one of which is FUS/TLS (fused in Ewing’s sarcoma/translocated in liposarcoma), a member of the TET protein family along with EWS, TLS and TAF15. EWS and TLS play an important role in gene regulation [11,12], originally described in myxoid/round cell liposarcoma [13], FUS is a multifuntional protein implicated in pre-mRNA splicing [14], chromosome stability [15], and gene transcription [16].
According to Haile et al. [17], FUS upregulates the transcriptional activity in prostate cancer cells due to its role as an androgen receptor (AR) co-activator. Prostatic adenocarcinoma depends on androgenic stimulation to progress, and AR stimulation activates the cell cycle, resulting in proliferation [18]. In contrast, Broke et al. [19] affirm that FUS expression is downregulated in response to AR activation and that upregulation of FUS expression retards prostate cancer cell growth in response to AR stimulation in vitro and in vivo, induces mitotic cell cycle arrest in G1 and induces apoptosis in a way resembling tumor suppression [19]. In their paper, Brooke et al. [19] found FUS expression on immunohistochemistry to be inversely correlated with Gleason score, patients with high levels of FUS survived longer. Whereas, FUS expression was associated with increased Odds Ratio and Hazard Ratio in Shipitsin et al. using a quantitative multiplex proteomics in situ imaging system [10]. The Human Protein Atlas reports no association with prostate cancer prognosis under the entry for FUS [20].
In this study, we evaluated FUS expression in non-neoplastic tissue and prostatic adenocarcinoma, the association between FUS expression and clinical/laboratory progression, and the ability of FUS expression to predict Gleason scores >6 in Gleason pattern 3 adenocarcinomas, and Gleason scores >7 (3 + 4) in Gleason pattern 4 adenocarcinomas.
Abstract
Introduction. CD44 has been proposed as a prognostic marker and a stem cell marker but studies in patients with prostate cancer have yielded inconsistent results. Patients and Methods. Patients submitted to radical prostatectomy between 2008 and 2013 at a university hospital were followed with biannual serum PSA tests to determine the biochemical recurrence (BR). Archived paraffin blocks with neoplastic and nonneoplastic tissue were evaluated immunohistochemically for a panCD44 and MYC. Results. Sixty-nine patients completed follow-up and were included. CD44 positivity was observed in inflammatory cells (42%), nonneoplastic epithelium (39.7%), and neoplastic tissue (12.3%). In nonneoplastic tissues staining was observed in basal and luminal cells with the morphology of terminally differentiated cells. In neoplastic tissues, CD44 negativity was correlated with higher Gleason scores (Rho = −0.204; ) and higher preoperative serum PSA levels when evaluated continuously (). CD44 expression was not associated with tumor stage (), surgical margin status (), or BR (), nor was there any association between CD44 and MYC expression in neoplastic tissue (). Conclusion. In the bulk of cells, the minority of cancer stem cells would not be detected by immunohistochemistry using panCD44. As a prognostic marker, its expression was weakly correlated with Gleason score and preoperative PSA level, but not with surgical margin status, tumor stage, or BR.
Acima Trabalho de Pesquisa desenvolvido no Programa de Pós Graduação em Ciências Medico Cirúrgicas da Faculdade de Medicina da Universidade Federal do Ceará
https://onlinelibrary.wiley.com/doi/10.1111/apm.13330
Prostate cancer is the world’s most frequently diagnosed malignancy in men. Recent work suggests that patients with high ERG expression intensity are significantly more likely to develop biochemical relapse and metastasis, and die of prostate cancer. The objective of this study was to determine the relationship between the intensity of ERG protein expression and the staging of prostate cancer and the formation of metastases in 635 samples. A retrospective cohort analysis was performed using immunohistochemistry reactions in tissue microarray samples taken from non-neoplastic and neoplastic prostate tissue from patients who underwent radical prostatectomies at a reference hospital from 2009 to 2016. For the ERG marker analysis, the samples were scored for the presence or absence of nuclear signals. Weak, moderate, or strong intensity of the nuclei of the observable tumor cells was considered to be positive markers. All told, 635 samples were evaluated, and the ERG expression was inconclusive in 9% of cases, while 30% were positive and 61% were negative. Of the samples with positive result: 25.8% were weak and focal, 53.2% were moderate, and 21% were strong. Finally, 21% of the cases with a positive ERG had a high Gleason score. Metastasis was detected in 41% of the patients who were ERG positive, and of these, the majority had moderate marking and were aged older than 60 years, although there was no statistically significant difference between the older and younger age groups. Patients with moderate to strong ERG staining had higher staging compared to the others, and no increase in metastasis was detected in patients with more intense ERG expression. More studies should be carried out to corroborate these results and to reach a consensus on the intensity and scoring of the expression levels of ERG markers.
Acima Trabalho de Pesquisa Realizado na Universidade Federal do Ceará Aluna de Mestrado Programa de Pos Graduação em Patologia Faculdade de MEdicina Universidade Federal do Ceará!
https://juniperpublishers.com/jojun/pdf/JOJUN.MS.ID.555734.pdf
Abstract Introduction: Prostate cancer is the second most frequent neoplasm in men. Recent studies suggest that the rate of microsatellite instabil) andimary prostate tumors is <4% and that the loss rate of the repair gene in these tumors is <3%. The objective was to characterize primary prostate tumors in terms of immunohistochemical staining of PMS2 and MSH6. Methods: There were 635 samples from patients with prostatic adenocarcinoma who underwent radical prostatectomy in a referral hospital. For this purpose, a retrospective cohort was constituted and immunohistochemical reactions were studied in tissue microarrays from samples taken from non-neoplastic and neoplastic tissues. Results: The rate of simultaneous positive labeling was 90.5% and no case had concomitant negative labeling. The Gleason score of patients with no marking of PMS2 or MSH6 after the review ranged from 2 to 4 and the pathological staging of the cases ranged from pT2 to pT3b.The group without MSH6 and/or PMS2 scores had higher Gleason scores, and those only without MSH6 score had worse staging conditions. There was a higher frequency of metastasis among patients without MSH6 labeling. Discussion/Conclusion: Age older than 60 years was not statistically significant in relation to the absence of PMS2 and MSH6.Negative labeling of MSH6 was related to biochemical recurrence. PMS2 and MSH6 gene expression was not associated with PSA levels above 10 ng/ml. The values of Gleason scores were higher in the unmarked group. There was a higher frequency of metastasis in patients without MSH6 labeling. The loss rate of the MSH6 repair gene in the sample was 0.15% and of PMS2 was 0.30%, Similar to literature data. More studies should be carried out to corroborate these findings. Keywords: Prostate cancer; PMS2; MSH6; Immunohistochemistry; Prostatectomy