Brachyury, a driver of epithelial mesenchymal transition, as an independent prognostic factor in high-grade testicular germ cell tumors.

e16039 Background: The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis and poor prognosis. However, its clinical association with testicular germ cell tumor (TGCT) is unknown. Methods: We analyzed the expression of Brachyury both at protein and transcript levels in a series of 96 TGCT samples and by in silico analysis, respectively. Additionally, we investigated the clinical significance of Brachyury in TGCT. Results: Brachyury protein showed to be over-represented in 89.6% (86/96) of TGCT cases with nuclear staining in 24% (23/96) of them. Microarray expression analysis in two independent cohorts of TGCTs showed similar results with increased levels of Brachyury in TGCTs and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk TGCTs. Multivariate analysis showed that Brachyury nuclear subcellular localization was an independent predictor of poor prognosis (HR: 3.56, p = 0.06). Conclusions: These results indicate that Brachyury plays an oncogenic role in TGCTs and its subcellular localization in the nucleus is a potential novel biomarker of poor prognosis and an oncotarget for intermediate/high-risk TGCTs treatment.

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METTL3 May Regulate Testicular Germ Cell Tumors Through EMT and Immune Pathways

Cell Transplantation ◽

10.1177/0963689720946653 ◽

2020 ◽

Vol 29 ◽

pp. 096368972094665

Author(s):

Yang Luo ◽

Yuan Sun ◽

Lei Li ◽

Yuling Mao

Keyword(s):

Molecular Markers ◽

Germ Cell ◽

Effective Treatment ◽

Epithelial Mesenchymal Transition ◽

Germ Cell Tumors ◽

Migration And Invasion ◽

Testicular Germ Cell Tumors ◽

Migration Ability ◽

Testicular Germ Cell ◽

Mesenchymal Transition

Testicular germ cell tumors (TGCTs) are highly prevalent in young men aged 20–40 years and are one of the most common lethal solid tumors in men of this age. Due to the current unclear mechanism of tumor development, there is a lack of effective treatment, and therefore in-depth research of the molecular mechanism of the occurrence and development of TGCT and the search for suitable and effective therapeutic targets and molecular markers are of great significance for achieving effective treatment. METTL3 is a very important methylase, which has been implicated in the progression of many cancers, but the role of METTL3 in TGCT has not been fully elucidated. In this article, we found that METTL3 expression was significantly downregulated in TGCT tissues, and patients with low expression levels had lower overall survival and relapse-free survival rates. After overexpressing METTL3, cell proliferation, invasion, and migration ability significantly increased, while influencing the expression of epithelial–mesenchymal transition (EMT)-related proteins. In addition, we observed that the expression level of METTL3 positively correlated with molecular markers and infiltration level of CD8+ and CD4+ T cells and natural killer cells. In sum, our findings identified that METTL3 can be used as an independent prognostic marker in patients with TGCT. METTL3 participates in the proliferation, migration, and invasion of TGCT cells by regulating the expression of EMT-related genes and may also play a role in activating the tumor immune response in TGCT.

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Overexpression of p75NTR in Testicular Germ Cell Tumors: a New Biomarker of Cancer Differentiation?

10.20944/preprints202103.0273.v1 ◽

2021 ◽

Author(s):

Anna Perri ◽

Vittoria Rago ◽

Rocco Malivindi ◽

Lorenza Maltese ◽

Danilo Lofaro ◽

...

Keyword(s):

Germ Cell ◽

Human Cancer ◽

Germ Cell Tumors ◽

Receptor Protein ◽

Specific Marker ◽

Nuclear Staining ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Cancer Types

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr=40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in tumor tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway, and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK, and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker of differentiation in TGCTs.

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Evaluation of inductor factors in the epithelial-mesenchymal transition (EMT) in testicular germ cell tumours (TGCT) and their roles in cisplatin resistance

European Urology Supplements ◽

10.1016/s1569-9056(19)32542-4 ◽

2019 ◽

Vol 18 (4) ◽

pp. 30-31

Author(s):

L.M.B. Tufi ◽

L.A.B. Pereira ◽

C.F.B. Alves ◽

L.S. Silva ◽

R.M. Reis ◽

...

Keyword(s):

Germ Cell ◽

Cisplatin Resistance ◽

Epithelial Mesenchymal Transition ◽

Germ Cell Tumours ◽

Testicular Germ Cell ◽

Mesenchymal Transition ◽

Testicular Germ Cell Tumours

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Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors

Andrology ◽

10.1111/andr.12495 ◽

2018 ◽

Vol 6 (4) ◽

pp. 597-604 ◽

Cited By ~ 4

Author(s):

F. Pinto ◽

F. M. Cárcano ◽

E. C. A. da Silva ◽

D. O. Vidal ◽

C. Scapulatempo-Neto ◽

...

Keyword(s):

High Risk ◽

Prognostic Factor ◽

Germ Cell ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell

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Long-Term Efficacy of Two Cycles of BEP Regimen in High-Risk Stage I Nonseminomatous Testicular Germ Cell Tumors with Embryonal Carcinoma and/or Vascular Invasion*1

European Urology ◽

10.1016/j.eururo.2004.03.022 ◽

2004 ◽

Vol 46 (2) ◽

pp. 209-215 ◽

Cited By ~ 61

Author(s):

C CHEVREAU

Keyword(s):

High Risk ◽

Germ Cell ◽

Vascular Invasion ◽

Embryonal Carcinoma ◽

Germ Cell Tumors ◽

Stage I ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Term Efficacy

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Epithelial-mesenchymal transition markers in malignant ovarian germ cell tumors

Apmis ◽

10.1111/apm.12715 ◽

2017 ◽

Vol 125 (9) ◽

pp. 781-786 ◽

Cited By ~ 1

Author(s):

Olesya Solheim ◽

Mette Førsund ◽

Claes G. Tropé ◽

Sigrid Marie Kraggerud ◽

Jahn M. Nesland ◽

...

Keyword(s):

Germ Cell ◽

Epithelial Mesenchymal Transition ◽

Germ Cell Tumors ◽

Mesenchymal Transition

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Overexpression of p75NTR in Human Seminoma: A New Biomarker?

Life ◽

10.3390/life11070629 ◽

2021 ◽

Vol 11 (7) ◽

pp. 629

Author(s):

Anna Perri ◽

Vittoria Rago ◽

Rocco Malivindi ◽

Lorenza Maltese ◽

Danilo Lofaro ◽

...

Keyword(s):

Human Cancer ◽

Germ Cell Tumors ◽

Receptor Protein ◽

Specific Marker ◽

Nuclear Staining ◽

Trka Receptor ◽

Testicular Germ Cell ◽

Cancer Types ◽

First Time

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs.

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OCT 4 immunohistochemistry in postpubertal cryptorchidism

Open Medicine ◽

10.2478/s11536-010-0074-x ◽

2011 ◽

Vol 6 (2) ◽

pp. 243-246

Author(s):

Ivan Krhen ◽

Tomislav Kulis ◽

Marijana Coric ◽

Nikola Knezevic ◽

Zvonimir Marekovic ◽

...

Keyword(s):

Testicular Cancer ◽

Germ Cell ◽

Immunohistochemical Staining ◽

Testicular Germ Cell Tumor ◽

Specific Marker ◽

Nuclear Staining ◽

Testicular Germ Cell ◽

Increased Risk ◽

Intratubular Germ Cell Neoplasia ◽

Work Up

AbstractPatients with cryptorchidism are at an increased risk for germ cell testicular cancer. OCT 4 has been shown to be a sensitive and specific marker for some types of germ cell testicular cancer. We undertook this study to establish whether OCT 4 immunohistochemistry is a useful tool in the pathohistologic evaluation of postpubertal patients with cryptorchidism. Seventeen postpubertal patients underwent orchidectomy for cryptorchidism at our center since 1997. Immunohistochemical staining with OCT 4 was performed on these samples. Characteristic OCT 4 nuclear staining was positive in two patients. One patient was correctly diagnosed on previous pathohistological evaluation, while OCT4 immunohistochemical staining revealed previously unidentified intratubular germ cell neoplasia in the other patient. OCT 4 immunohistochemistry can be useful in diagnosing a testicular germ cell tumor in patients with cryptorchidism. If we consider a low number of postpubertal patients with cryptorchidism a benefit of immunohistochemical staining with OCT4, this could favor the use of OCT 4 staining in work-up of cryptorchidism.

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