25 oktober 2017:
Aanvullend op onderstaande studie van maart 2005 van Nederlandse oncologen: Testicular germ-cell tumours in a broader perspective (zie hieronder abstract en samenvatting van conclusies) is het interessant deze studie: Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer te bekijken. Deze studie geeft uitstekend overzicht van wat bepaalde behandelingen bij teelbalkanker voor resultaat geven en welke zinloos lijken. (abstract staat onderaan artikel)
Nog interessanter is deze studie waarin bepaalde markers in het bloed voorspellende waarde hebben op de diagnsoe en aanslaan van een behandeling en zelfs op kansen op overall overleving: Accurate primary germ cell cancer diagnosis using serum based microRNA detection (ampTSmiR test)
The largest series evaluated so far, demonstrate that detection of the embryonic stem cell miR-371a-3p, 373-3p and 367-3p is highly informative to diagnose patients with a primary TGCC.
Figure 2
A. Diagnostic accuracy of circulating miR-371a-3p, 373-3p and 367-3p were analyzed by ROC curves. The data shown in Figure Figure11 were used to draw the ROC plots. The Area Under the Curve (AUC) varied from 0.861 to 0.951. B. ROC curves generated of combinations of the different miR analyses. The AUC varied from 0.915 to 0.962 for combination of the miRs. C. ROC analysis generated separately for sera of SE and NS patients. The AUC varied from 0.920 to 0.968 for NS and from 0.809 to 0.957 for SE.
Onderaan dit artikel staat het abstract van bovengenoemde studie met referentielijst.
1 maart 2005:: Bron: Nature Reviews Cancer 5, 210-222 (2005); doi:10.1038/nrc1568
Nederlandse artsen en wetenschappers maakten een overzicht van de behandelmogelijkheden bij teelbalkanker - germcancer en vooral waarom deze vorm van kanker zo goed te behandelen is met chemokuren. Hier het abstract uit Nature van deze week. Onderaan artikel staat korte autobiografie van de Nederlandse auteurs. Wie wil betalen kan het volledige artikel ook opvragen bij Nature.
TESTICULAR GERM-CELL TUMOURS IN A BROADER PERSPECTIVE
J. Wolter Oosterhuis & Leendert H. J. Looijenga.
Abstract
The germ-cell tumours are a fascinating group of neoplasms because of their unusual biology and the spectacular therapeutic results that have been obtained in these tumours. Traditionally, this group of neoplasms is presented in an organ-oriented approach. However, recent clinical and experimental data convincingly demonstrate that these neoplasms are one disease with separate entities that can manifest themselves in different anatomical sites. We propose five entities, in which the developmental potential is determined by the maturation stage and imprinting status of the originating germ cell. Recent progress begins to explain the apparent unpredictable development of germ-cell tumours and offers a basis for understanding their exquisite sensitivity to therapy.
Summary
- Germ-cell tumours (GCTs) of all anatomical sites can be classified into five groups, characterized by their chromosomal complement and developmental potential.
- The most significant recurrent chromosomal aberrations in type I yolk-sac tumours are loss of 1p, 4 and 6q, and gain of 1q, 12(p13) and 20q. In type II seminomas and non-seminomatous GCTs, the most significant recurrent chromosomal aberrations are gain of 7, 8, 12p, 21 and X, and loss of chromosomes 1p, 11, 13 and 18. Aberrations of 12p are the only recurrent structural abnormalities in type II GCTs. In type III spermatocytic seminomas, gain of chromosome 9 is most common.
- The originating cell is most probably a primitive germ cell of which the developmental potential differs according to its stage of maturation and pattern of genomic imprinting.
- Animal models are available for the different groups of GCTs, except for the type II seminomas and non-seminomatous GCTs.
- An activating KIT mutation in codon 816 is an early pathogenetic event in bilateral testicular seminomas and non-seminomatous GCTs.
- The transcription factor OCT3/4, a characteristic of primordial germ cells and pluripotent stem cells, is a new and robust diagnostic marker for type II seminomas and non-seminomatous GCTs, including their intratubular precursor.
- Treatment sensitivity and resistance of GCTs probably correlates with retention and loss of embryonic characteristics (in particular, DNA-repair deficiency), respectively.
Author biographies
J. Wolter Oosterhuis, a professor of pathology, studied medicine and trained as a pathologist at Groningen University, Groningen, the Netherlands. He moved to Rotterdam in 1990 to become the scientific director of the Daniel den Hoed Cancer Center. Since 1998 he has been Head of the Department of Pathology — part of the Josephine Nefkens Institute — of the Erasmus University Medical Center Rotterdam, the Netherlands. Additional functions include scientific director of the postgraduate school Molecular Medicine of the Erasmus Medical Center, and of the Daniel den Hoed Cancer Foundation. His main research interests are the pathobiology and therapy resistance of gonadal and extra-gonadal germ-cell tumours.
Leendert H. J. Looijenga, an associate professor, graduated cum laude in human biology at Groningen University. In 1990 he moved to Rotterdam, and jointly with Wolter Oosterhuis established a research group to study the pathobiology of germ-cell tumours. In 1994 he submitted his thesis on this subject. In 1998 his research group moved to the Josephine Nefkens Institute, to become part of the Department of Pathology of the Erasmus University Medical Center Rotterdam. His main research interests are the pathobiology and therapy resistance of gonadal and extra-gonadal germ-cell tumours; the pathology of dysgenetic gonads; and ploidy-regulated genes in human neoplasia.
detection of the embryonic stem cell miR-371a-3p, 373-3p and 367-3p is highly informative to diagnose patients with a primary testicular germ cell cancer (TGCC).
Accurate primary germ cell cancer diagnosis using serum based microRNA detection (ampTSmiR test)
Abstract
Multiple studies, including various methods and overall limited numbers of mostly heterogeneous cases, indicate that the level of embryonic stem cell microRNAs (miRs) (e.g. 371a-3p, 372-3p, 373-3p, and 367-3p) are increased in serum at primary diagnosis of almost all testicular germ cell cancer (TGCC).
Here we determine the status of three of these miRs in serum samples of 250 TGCC patients, collected at time of primary diagnosis, compared with 60 non-TGCC patients and 104 male healthy donors. The levels of miRs were measured by the robust ampTSmiR test, including magnetic bead-based miR isolation and target specific pre-amplification followed by real-time quantitative PCR (RT-qPCR) detection. Calibration is performed based on the non-human spike-in ath-miR-159a, and normalization on the endogenous control miR-30b-5p.
The serum levels of miR-371a-3p, 373-3p, and 367-3p are informative to accurately detect TGCC patients, both seminomas and non-seminomas, at the time of primary diagnosis (p< 0.000). Receiver Operating Characteristic (ROC) analysis demonstrate that the Area Under the Curve (AUC) for miR-371a-3p is 0.951 (being 0.888 for miR-373-3p and 0.861 for miR-367-3p), with a sensitivity of 90%, and a specificity of 86% (positive predictive value of 94% and negative predictive value of 79%). Inclusion of miR-373-3p and 367-3p resulted in a AUC of 0.962, with a 90% sensitivity and 91% specificity. Similar results were obtained using the raw Ct data. Importantly, the results demonstrate that ampTSmiR is not suitable to detect pure teratoma as well as the precursor of TGCC, i.e., Germ Cell Neoplasia In Situ (GCNIS).
The largest series evaluated so far, demonstrate that detection of the embryonic stem cell miR-371a-3p, 373-3p and 367-3p is highly informative to diagnose patients with a primary TGCC.
REFERENCES
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