PARP expression in germ cell tumours

2013 ◽  
Vol 66 (7) ◽  
pp. 607-612 ◽  
Author(s):  
Michal Mego ◽  
Zuzana Cierna ◽  
Daniela Svetlovska ◽  
Dusan Macak ◽  
Katarina Machalekova ◽  
...  

BackgroundPoly(ADP-ribose)polymerase (PARP) inhibitors represent a new class of promising drugs in anticancer therapy.AimsTo evaluate PARP expression in testicular germ cell tumours (GCTs) and to correlate expression patterns with clinicopathological variables.MethodsIn this translational study, tumour specimens from 124 patients with GCTs (114 patients with testicular primary tumours and 10 with extragonadal GCTs) were identified. PARP expression was detected by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method and compared to PARP expression in normal testicular tissue.ResultsWe observed higher expression of PARP in testicular tumours compared to normal testicular tissue (mean QS=10.04 vs 3.31, p<0.0000001). Mean QS±SD for each histological subtype was as follows: intratubular germ cell neoplasia unclassified (IGCNU)=18.00±0.00, embryonal carcinoma=9.62±5.64, seminoma=9.74±6.51, yolk sac tumour=7.8±7.20, teratoma=5.87±5.34, and choriocarcinoma=4.50±8.33. The PARP overexpression (QS>9) was most often detected in IGCNU (100% of specimen with PARP overexpression), seminona (52.6%), embryonal carcinoma (47.0%), yolk sac tumour (33.3%), teratoma (26.7%) and choriocarcinoma (25.0%), compared to 1.9% of normal testicular tissue specimens. There was no association between PARP expression and clinical variables.ConclusionsIn this pilot study, we showed for the first time, that PARP is overexpressed in testicular germ cell tumours compared to normal testis.

2010 ◽  
pp. 461-467
Author(s):  
George Samandouras

Chapter 8.14 covers germ cell tumours, including germinoma, embryonal carcinoma, yolk sac tumour, choriocarcinoma, and teratomas.


2007 ◽  
Vol 97 (12) ◽  
pp. 1707-1712 ◽  
Author(s):  
A McIntyre ◽  
B Summersgill ◽  
Y J Lu ◽  
E Missiaglia ◽  
S Kitazawa ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15027-e15027
Author(s):  
Michal Mego ◽  
Zuzana Cierna ◽  
Daniela Svetlovska ◽  
Dusan Macak ◽  
Katarina Machalekova ◽  
...  

e15027 Background: Testicular germ-cell tumours (TGCTs) represent a model for the cure of cancer. Nonetheless, a small proportion of patients develop disease recurrence. PARP inhibitors represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate poly(ADP-ribose)polymerase-1 (PARP1) expression in TGCTs and to correlate expression patterns with clinico-pathological variables. Methods: In this translational study, tumor specimens from 124 patients with GCTs were identified. PARP1 expression was detected by immunohistochemistry using monoclonal antibody, scored by the multiplicative quickscore (QS) method and compared to PARP1 expression in testicular tissue of normal testis. The QS was calculated by multiplying the percentage score by the staining intensity score to yield a minimum value of 0 and a maximum value of 18. Based on the QS nuclear PARP1 expression was graded as low (0–9) or high (10–18). Results: We observed higher expression of PARP1 in testicular tumors compared to normal tissue of testis (mean QS = 10.04 vs. 3.60, p < 0.0000001). Mean QS ± SD for each histological subtype was following: intratubular germ cell neoplasia (ITGCN) = 18.00 ± 0.00, embryonal carcinoma = 9.62 ± 5.64, seminoma = 9.74 ± 6.51, yolc sac tumor = 7.8 ± 7.20, teratoma = 5.87 ± 5.34, and choriocarcinoma = 4.50 ± 8.33. The PARP1 overexpression (QS > 9) was most often detected in ITGCN (100% of specimen with PARP1 overexpression), seminona (52.6%), embryonal carcinoma (47.0%), yolc sac tumor (33.3%), teratoma (26.7%), and choriocarcinoma (25.0%), compared to 1.9% of normal testicular tissue specimen. There was no association between PARP1 expression and clinical variables. Conclusions: PARP1 overexpression is an early event in the development of TGCTs. We suggest that PARP1 could represent a novel treatment target in TGCTs and the assessment of PARP1 expression in tumor samples may lead to the consideration of TGCTs patients for PARP inhibitor therapy.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1325
Author(s):  
Abhisek Ghosh ◽  
Korsuk Sirinukunwattana ◽  
Nasullah Khalid Alham ◽  
Lisa Browning ◽  
Richard Colling ◽  
...  

Testicular cancer is the most common cancer in men aged from 15 to 34 years. Lymphovascular invasion refers to the presence of tumours within endothelial-lined lymphatic or vascular channels, and has been shown to have prognostic significance in testicular germ cell tumours. In non-seminomatous tumours, lymphovascular invasion is the most powerful prognostic factor for stage 1 disease. For the pathologist, searching multiple slides for lymphovascular invasion can be highly time-consuming. The aim of this retrospective study was to develop and assess an artificial intelligence algorithm that can identify areas suspicious for lymphovascular invasion in histological digital whole slide images. Areas of possible lymphovascular invasion were annotated in a total of 184 whole slide images of haematoxylin and eosin (H&E) stained tissue from 19 patients with testicular germ cell tumours, including a mixture of seminoma and non-seminomatous cases. Following consensus review by specialist uropathologists, we trained a deep learning classifier for automatic segmentation of areas suspicious for lymphovascular invasion. The classifier identified 34 areas within a validation set of 118 whole slide images from 10 patients, each of which was reviewed by three expert pathologists to form a majority consensus. The precision was 0.68 for areas which were considered to be appropriate to flag, and 0.56 for areas considered to be definite lymphovascular invasion. An artificial intelligence tool which highlights areas of possible lymphovascular invasion to reporting pathologists, who then make a final judgement on its presence or absence, has been demonstrated as feasible in this proof-of-concept study. Further development is required before clinical deployment.


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