High immunoexpression of Ki67, EZH2, and SMYD3 in diagnostic prostate biopsies independently predicts outcome in patients with prostate cancer

Lobo, João; Rodrigues, Ângelo; Antunes, Luís; Graça, Inês; Ramalho-Carvalho, João; Vieira, Filipa Quintela; Martins, Ana Teresa; Oliveira, Jorge; Jerónimo, Carmen; Henrique, Rui

doi:10.1016/j.urolonc.2017.10.028

Cited by 46 publications

(39 citation statements)

References 36 publications

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“…Furthermore, the biggest challenge is perhaps the one related to overtreatment: there is an urgent need for accurate predictive biomarkers of this disease, that may identify which patients will experience disease relapse, requiring more strict follow-up and adjuvant treatments [111]. This is a result, in great part, of the wide access to serum prostate-specific antigen (PSA) screening, responsible for detecting over 80% of PCa at localized stage, which displays excellent outcome [112].…”

Section: Major Clinical Challengesmentioning

confidence: 99%

“…From a therapeutic point of view, LSD1 (a lysine histone demethylase) has proved to be an interesting target, since its inhibitors were effective in preventing CRPC tumor growth in vitro and in vivo [137]. EZH2, which associates with poor prognostic features and worse patient outcome [112], is another target worth exploring. Moreover, both demethylating agents such as azacitidine, HDAC inhibitors such as vorinostat and even novel agents such as the pan-bromodomain inhibitor JQ1 have shown antitumor effect in prostate cancer models, including CRPC [138][139][140].…”

Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

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Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

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Section: Major Clinical Challengesmentioning

confidence: 99%

Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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“…Высокие показатели экспрессии данного белка гораздо чаще встречались у пациентов с более поздними стадиями заболевания, в настоящем исследовании доказана прямая корреляционная связь данного показателя и экстрапростатического распространения опухоли, характерного для поздних стадий. Полученные данные согласуются с результатами других исследований, свидетельствующих о том, что высокие показатели пролиферативной активности клеток связаны с риском формирования рецидива, прогрессирования и смертельного исхода у больных раком предстательной железы [16,17].…”

Section: Discussionunclassified

Immunohistochemical Study of Tumor Cells Proliferative Activity at Different Graduations of Prostate Cancer

Kudryavtsev

Кудрявцев²,

Kudryavtseva

et al. 2019

Vestn. Ross. univ. družby nar., Ser. Med.

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Prostate cancer is one of the leading causes of men death in developed countries. Modern diagnostic methods, including a puncture biopsy of the prostate gland, make it possible to verify oncology in the early stages, however, routine studies do not always allow to predict the course of the disease and outcome. The aim of our study was to analyze the clinical, morphological and immunohistochemical features of the proliferative activity of adenocarcinoma cells using the Ki-67 marker, to compare the degree of proliferative activity in tumors of various degrees of malignancy (according to Gleason’s classification), as well as to compare this indicator with the clinical stage of the disease, the level of prostate-specific antigen in the blood, the size of the prostate gland. Materials and Methods: On the basis of the City Clinical Hospital No. 31 and the Veteran Hospital No. 2, paraffin blocks with material obtained as a result of prostate biopsy, transurethral resection, and radical prostatectomy were selected. A morphological and immunohistochemical study of the material with the Ki-67 marker and a quantitative assessment of the degree of proliferative activity were carried out. Data were analyzed using the STATISTICA 10.0 program using estimates of the normality of the data distribution according to the Shapiro-Wilk W-test, the significance of differences was estimated using the Mann-Whitney U-test, and correlation relationships using Spearman’s correlation coefficient. Results: Statistically significant differences in the degree of proliferative activity in groups differing in the degree of differentiation were revealed. A statistically significant direct correlation of moderate severity was revealed when comparing proliferative activity with the degree of differentiation according to the Gleason system (rs = 0.523) and the clinical stage of the disease (rs = 0.646). No statistically significant correlation was found between indicators such as prostate-specific antigen level, age, prostate volume, and proliferative activity index. Conclusion: taking into account the proliferative activity index in addition to clinical and morphological studies helps to diagnose and subsequently predict the course of prostate cancer.

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“…In this retrospective study, a cohort of TGCT patients (already reported and validated by us 21 Figure S1, which has been adapted from Lobo et al 28…”

Section: Patients and Sample Collectionmentioning

confidence: 99%

p53 and MDM2 expression in primary and metastatic testicular germ cell tumors: Association with clinical outcome

et al. 2020

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Background Testicular germ cell tumors (TGCTs) are highly sensitive to platinum‐based chemotherapy, and wild‐type p53 seems to play a pivotal role in this susceptibility. On the other hand, overexpression of MDM2 seems to entail treatment resistance and unfavorable prognosis. Objectives We aimed to describe p53 and MDM2 immunoexpression in a well‐characterized cohort of primary and metastatic TGCTs and evaluate associations with clinicopathological and prognostic variables, including survival. Materials and methods 237 primary tumor samples and 12 metastases were evaluated for p53 and MDM2 immunoexpression using digital image analysis. Clinical records of all patients were reviewed for baseline clinical/pathologic characteristics and follow‐up. Results A significant positive correlation between p53 and MDM2 H‐scores was found (rs = 0.590, P < .0001). Non‐seminomas showed significantly higher expression levels of both p53 and MDM2 (P = .0002, P < .0001), which peaked in embryonal carcinomas and choriocarcinomas. Percentage of immunoexpressing cells and H‐score were significantly higher in chemo‐treated metastases compared with chemo‐naïve primary tumors for MDM2 (P ≤ .0001 for both), but not for p53 (P = .919 and P = .703, respectively). Cases with higher MDM2 immunoexpression showed a statistically significant trend for association with poorer prognosis (P = .043). Relapse/progression‐free survival at 12 months post‐diagnosis was lower in the “MDM2‐high” (≥P50) vs. the “MDM2‐low” (

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High immunoexpression of Ki67, EZH2, and SMYD3 in diagnostic prostate biopsies independently predicts outcome in patients with prostate cancer

Cited by 46 publications

References 36 publications

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Immunohistochemical Study of Tumor Cells Proliferative Activity at Different Graduations of Prostate Cancer

p53 and MDM2 expression in primary and metastatic testicular germ cell tumors: Association with clinical outcome

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