Serumspiegel von MicroRNA-371a-3p (M371-Test) als neuer Biomarker für testikuläre Keimzelltumoren: Ergebnisse einer prospektiven Multicenterstudie

2021 ◽  
pp. 1-10
Author(s):  
Klaus-Peter Dieckmann ◽  
Arlo Radtke ◽  
Lajos Geczi
Keyword(s):  
Germ Cell ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Germ Cell Tumors ◽  
Sensitivität Und Spezifität ◽  
Humanes Choriongonadotropin ◽  
Testikuläre Keimzelltumoren ◽  
Β Hcg ◽  
Systemische Erkrankung ◽  
Stadium I

<b>Zielsetzung:</b> Die Ergebnisse früherer Studien deuteten darauf hin, dass die Serumspiegel der microRNA (miR)-371a-3p (so genannter M371-Test) eine sehr viel höhere Sensitivität und Spezifität aufweisen als die klassischen Tumormarker für testikuläre Keimzelltumoren (germ cell tumors, GCTs) und sowohl für Seminome als auch für Nichtseminome anwendbar sind. Unser Ziel war es, den Nutzen dieses Tests als neuen Biomarker für GCTs zu bestätigen. <b>Patienten und Methoden:</b> Im Rahmen einer prospektiven Multicenter-Studie wurden die Serumspiegel von miRNA-371a-3p (miR-Spiegel) in Serumproben von 616 Patienten mit testikulären GCTs und 258 männlichen Kontrollen mittels quantitativer Polymerase-Kettenreaktion untersucht. Die GCT-Patientenpopulation umfasste 359 Patienten mit Seminom und 257 mit einem Nichtseminom; 371 hatten eine Erkrankung im klinischen Stadium I, 201 hatten eine systemische Erkrankung und 46 ein Rezidiv. Bei 424 Patienten erfolgten paarige Messungen vor und nach der Orchiektomie und bei 118 Patienten mit systemischer Erkrankung wurden serielle Messungen während der Behandlung durchgeführt. Die miR-Spiegel wurden mit denen von β-HCG (humanes Choriongonadotropin), α-Fetoprotein und Laktatdehydrogenase verglichen. <b>Ergebnisse:</b> Bei der GCT-Primärdiagnose betrug die Sensitivität des M371-Tests 90,1 %, die Spezifität 94,0 %, die Fläche unter der Kurve 0,966 in der Receiver-Operating-Characteristic-Analyse und der positive prädiktive Wert 97,2 %. Die Sensitivität von α-Fetoprotein, humanem β-Choriongonadotropin und Laktatdehydrogenase lag bei Seminomen bei weniger als 50 % und bei Nichtseminomen geringfügig höher. Es bestand eine signifikante Assoziation zwischen den miR-Spiegeln und dem klinischen Stadium, der Größe des Primärtumors und dem Ansprechen auf die Behandlung. Bei Rezidiven waren erhöhte miR-Spiegel zu beobachten, die anschließend bei einer Remission auf den Normalwert abfielen. Teratome exprimierten keine miR-371a-3p. <b>Schlussfolgerung:</b> Mit einer Sensitivität und Spezifität von mehr als 90 % schneidet der M371-Test besser ab als die klassischen GCT-Tumormarker. Alle histologischen Subgruppen mit Ausnahme des Teratoms exprimieren diesen Tumormarker. Nach weiterer Validierung könnte der Test für den klinischen Einsatz in Betracht kommen.

Risikoabschätzung einer akuten Exazerbation bei COPD-Patienten im Rahmen einer pneumologischen Anschluss-Rehabilitation anhand der Prävalenz und Schwergradausprägung von Komorbiditäten

Pneumologie ◽  
2021 ◽  
Author(s):  
P. Luu ◽  
S. Tulka ◽  
S. Knippschild ◽  
W. Windisch ◽  
M. Spielmanns
Keyword(s):  
Receiver Operating Characteristic ◽  
Charlson Comorbidity Index ◽  
Operating Characteristic ◽  
Rating Scale ◽  
Area Under The Curve ◽  
Sensitivität Und Spezifität ◽  
Comorbidity Index ◽  
Receiver Operating

Zusammenfassung Einleitung Akute COPD-Exazerbationen (AECOPD) im Rahmen einer pneumologischen Rehabilitation (PR) sind häufige und gefährliche Komplikationen. Neben Einschränkungen der Lebensqualität führen sie zu einem Unterbrechung der PR und gefährden den PR-Erfolg. Eine Abhängigkeit zwischen dem Krankheitsstatus und einem erhöhten Risiko für eine AECOPD ist beschrieben. Dabei stellt sich die Frage, ob der Charlson Comorbidity Index (CCI) oder die Cumulative Illness Rating Scale (CIRS) dafür geeignet sind, besonders exazerbationsgefährdete COPD-Patienten in der PR im Vorfeld zu detektieren. Patienten und Methoden In einer retrospektiven Untersuchung wurden die Daten von COPD-Patienten, welche im Jahr 2018 eine PR erhielten, analysiert. Primärer Endpunkt der Untersuchung war die Punktzahl im CCI. Alle Daten wurden dem Klinikinformationssystem Phönix entnommen und COPD-Exazerbationen erfasst. Die laut Fallzahlplanung benötigten 44 Patienten wurden zufällig (mittels Zufallsliste für jede Gruppe) aus diesem Datenpool rekrutiert: 22 Patienten mit und 22 ohne Exazerbation während der PR. CCI und CIRS wurden für die eingeschlossenen Fälle für beide Gruppen bestimmt. Die Auswertung des primären Endpunktes (CCI) erfolgte durch den Gruppenvergleich der arithmetischen Mittel und der Signifikanzprüfung (Welch-Tests). Weitere statistische Lage- und Streuungsmaße wurden ergänzt (Median, Quartile, Standardabweichung).Zusätzlich wurde mittels Receiver Operating Characteristic (ROC)-Analyse sowohl für den CCI als auch für den CIRS ein optimaler Cutpoint zur Diskriminierung in AECOPD- und Nicht-AECOPD-Patienten gesucht. Ergebnisse 244 COPD-Patienten erhielten eine stationäre PR von durchschnittlich 21 Tagen, wovon 59 (24 %) während der PR eine behandlungspflichtige AECOPD erlitten. Die ausgewählten 22 Patienten mit einer AECOPD hatten einen mittleren CCI von 6,77 (SD: 1,97) und die 22 Patienten ohne AECOPD von 4,32 (SD: 1,17). Die Differenz von –2,45 war zu einem Signifikanzniveau von 5 % statistisch signifikant (p < 0,001; 95 %-KI: [–3,45 ; –1,46]). Die ROC-Analyse zeigte einen optimalen Cutpoint für den CCI bei 6 mit einer Sensitivität zur Feststellung einer AECOPD von 81,8 % und einer Spezifität von 86.,4 % mit einem Wert der AUC (area under the curve) von 0,87. Der optimale Cutpoint für den CIRS war 19 mit einer Sensitivität von 50 %, einer Spezifität von 77,2 % und einer AUC von 0,65. Schlussfolgerung COPD-Patienten mit einer akuten Exazerbation während der pneumologischen Rehabilitation haben einen höheren CCI. Mithilfe des CCI lässt sich mit einer hohen Sensitivität und Spezifität das Risiko einer AECOPD von COPD-Patienten im Rahmen eines stationären PR-Programms einschätzen.

Molecular dissection of primary mediastinal germ cell tumors.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 417-417 ◽  
Author(s):  
Lucia Nappi ◽  
Matti Annala ◽  
Gillian Vandekerkhove ◽  
Ladan Fazli ◽  
Martin Gleave ◽  
...  
Keyword(s):  
Germ Cell ◽  
Mutation Rate ◽  
Poor Prognosis ◽  
Germ Cell Tumors ◽  
Synonymous Mutation ◽  
Cancer Genes ◽  
Chromosome 12P ◽  
Pre Treatment ◽  
Β Hcg ◽  
Poor Outcomes

417 Background: Mediastinal non-seminomas (M-NS) have a poor prognosis compared to non-M-NS germ cell tumours (GCT) (i.e. primary gonadal or mediastinal seminomas (PG-S and M-S) and primary gonadal non-seminoma (PG-NS). M-NS tumors, while having pathological and serological similarity to other nonseminomas, are clinically and biological distinct and are considered IGCCC poor risk. In this study we aimed to evaluate the somatic mutation rate and prevalence of actionable/informative mutations in M-NS compared to M-S and primary GCT to inform consideration of targeted/precision therapy in these patients. Methods: Pre-treatment formalin fixed paraffin embedded specimens were collected from eleven patients with mediastinal and primary GCT patients (4 M-NS, 2 M-S, 3 PG-NS and 2 PG-S). High-density tumor areas were selected for DNA extraction and targeted sequencing of 578 established pan-cancer genes was performed (Roche Nimblegen SeqCaP EZ Comprehensive Cancer Design). Results: Consistent with the known landscape of testicular cancer, we identified five tumors with amplification of chromosome 12p, as well as hotspot mutations in KIT (n = 2) and KRAS (n = 1). Three of the 4 M-NS tumors had a non-synonymous mutation rate > 1 per Mb, which is higher than the primary TGCT and M-S sequenced here (range 0-0.5 per Mb) and the established low mutation rate for TGCT of 0.3-0.9 mutations/Mb. Mutations in TP53 (n = 2) and PTEN (n = 1) were only identified in patients with M-NS. The 2 patients with a TP53 mutation had a high non-synonymous mutation rate (1.3/Mb and 7.3/Mb), extensive metastatic disease with liver metastasis and high tumor markers (β-HCG: 1281 IU/L and α-FPT: 8500 ng/ml) at diagnosis. Both died of their disease and were the only patients in the cohort to have died. Conclusions: This study suggests that M-NS GCTs harbour more somatic alterations than non-M-NS GCTs, potentially underlying their poor prognosis. Our data are consistent with previous reports of an association between TP53 mutations and poor outcomes. Confirmation of our findings could lead to multi-center studies of targeted/precision therapies in patients with M-NS.

scholarly journals Study of clinical significance and histopathological correlation of serum β- hCG level

2017 ◽  
Vol 5 (6) ◽  
pp. 2310
Author(s):  
Faruq Ibrahimbhai Mulla ◽  
Kailash Sukhram Inaniya
Keyword(s):  
Germ Cell ◽  
Tumor Marker ◽  
Spontaneous Abortion ◽  
Germ Cell Tumors ◽  
Gestational Trophoblastic Disease ◽  
P Value ◽  
Trophoblastic Disease ◽  
Ectopic Gestation ◽  
Β Hcg ◽  
Malignant Germ Cell Tumors

Background: β-hCG is a marker useful in diagnosis of gestational trophoblastic disease (GTD), ectopic gestation (EG), spontaneous abortion (SA) and malignant germ cell tumors (MGCT) and it is helpful to clinician as an excellent tumor marker. It is useful to monitor treatment whether tumor is responding to treatment or the disease is progressing.Methods: β-hCG is a marker useful in diagnosis of gestational trophoblastic disease (GTD), ectopic gestation (EG), spontaneous abortion (SA) and malignant germ cell tumors (MGCT) and it is helpful to clinician as an excellent tumor marker. It is useful to monitor treatment whether tumor is responding to treatment or the disease is progressing.Results: p value is highly significant in Gestational Trophoblastic Diseases, EG and SA, as p value is < 0.005 in all these three categories. But in case of MGCT it is 0.452 which is not significant because study group was very small and one case who developed recurrence affected the value significantly. These findings suggest that β-hCG has definitive prognostic role (p value<0.005) in GTD, EG and SA.Conclusions: ELISA is rapid, sensitive, reliable and cost effective test for measurement of β-hCG. Pre-and post-therapeutic β-hCG serum levels seem to be useful in the therapy monitoring of trophoblastic gynaecological conditions i.e. GTD, EG and SA.

scholarly journals Retroperitoneal Leiomyosarcoma Associated with an Elevated β-HCG Serum Level Mimicking Extragonadal Germ Cell Tumor

Sarcoma ◽  
2000 ◽  
Vol 4 (4) ◽  
pp. 179-181 ◽  
Author(s):  
Michael Froehner ◽  
Hans-Juergen Gaertner ◽  
Andreas Manseck ◽  
Sven Oehlschlaeger ◽  
Manfred P. Wirth
Keyword(s):  
Serum Level ◽  
Germ Cell ◽  
Tumor Markers ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Soft Tissue Sarcomas ◽  
Retroperitoneal Tumor ◽  
Cell Tumor ◽  
Β Hcg ◽  
Primary Retroperitoneal

Patient.A 65-year-old man was admitted with a large primary retroperitoneal tumor and an increased β-human chorionic gonadotropin (β-HCG) serum level. A germ cell tumor was suspected; however, a computed tomography-guided biopsy failed to enable tumor classification. After two courses of chemotherapy, the β-HCG serum level had returned to the normal level and a diagnostic laparotomy with incisional biopsy was performed. The immunohistochemical examination of the specimen identified the tumor as a retroperitoneal pleomorphic leiomyosarcoma.Discussion.Tumor markers play only a marginal role in the work-up of patients with soft tissue sarcomas. In men with suspected retroperitoneal sarcomas, however, the determination of germ cell tumor markers occasionally enables a preoperative distinguishing of primary retroperitoneal germ cell tumors with considerable consequences for management. In this setting, a retroperitoneal tumor associated with a moderately elevated β-HCG is a diagnostic dilemma, and surgeons should be aware of the pitfall of a β-HCG-producing leiomyosarcoma in the differential diagnosis.

scholarly journals An update on the clinical diagnostic value of β-hCG and αFP for intracranial germ cell tumors

2016 ◽  
Vol 21 (1) ◽  
Author(s):  
Mingming Hu ◽  
Hongzhi Guan ◽  
Ching C. Lau ◽  
Keita Terashima ◽  
Zimeng Jin ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Diagnostic Value ◽  
Clinical Diagnostic ◽  
Intracranial Germ Cell Tumors ◽  
Β Hcg

scholarly journals A Case of HCG-Mediated Hyperthyroidism Related to Metastatic Choriocarcinoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A907-A908
Author(s):  
Samantha C Sovich ◽  
Dave K Garg ◽  
Run Yu
Keyword(s):  
Germ Cell ◽  
Best Practice ◽  
Clinical Case ◽  
Germ Cell Tumors ◽  
Clinical Endocrinology ◽  
Thyroid Stimulating Hormone ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Official Journal ◽  
Β Hcg

Abstract Introduction: We present a clinical case of a non-seminomatous germ cell choriocarcinoma producing human chorionic gonadotrophin (HCG) and inducing hyperthyroidism. Clinical Case: A 21-year-old male with recently diagnosed metastatic non-seminomatous germ cell choriocarcinoma presented with persistent tachycardia and anxiety. At diagnosis, his β- human chorionic gonadotrophin (β-HCG) was elevated to 6,435 mIU/mL (normal &lt;1 in male) and thyroid-stimulating hormone (TSH) was within normal limits. At presentation, however, his β-HCG increased to 103,229 mIU/mL, TSH was suppressed &lt;0.02 mcIU/mL (normal 0.3-4.7), and free thyroxine was elevated (FT4) 2.6 ng/dL (normal 0.8-1.7). His thyrotoxicosis improved with initiation of methimazole; however, his TSH remained undetectable due to persistently elevated β-HCG levels. His course was complicated by hemorrhagic shock and acute liver injury in the setting of a presumed intraluminal gastric metastasis, necessitating the discontinuation of methimazole. He was continued on steroids to try to minimize T4 to T3 conversion, but ultimately his thyroid hormones uptrended. He became stable enough to tolerate 5 days of chemotherapy, after which his FT4 quickly normalized. Unfortunately, he continued to suffer from vasodilatory shock and ultimately passed away. Discussion: It has been demonstrated that HCG can bind to the TSH receptor and has thyrotropic activity. The development of hyperthyroidism requires HCG levels &gt;200,000 mIU/mL that are sustained for several weeks (1). It is unknown what the prevalence of hyperthyroidism is in choriocarcinoma, but it has been shown to greatly increase when serum HCG levels are greater than &gt;50,000 mIU/mL (2). Conclusion: Hyperthyroidism can be difficult to recognize in patients suffering from cancer as many of the typical symptoms can also be seen with active malignancy. Patients with HCG-secreting tumors should be evaluated for hyperthyroidism and may benefit from treatment until the underlying cause can be managed. References: (1) Hershman, Jerome M. “Physiological and Pathological Aspects of the Effect of Human Chorionic Gonadotropin on the Thyroid.” Best Practice & Research Clinical Endocrinology & Metabolism, Baillière Tindall, 19 May 2004, www.sciencedirect.com/science/article/abs/pii/S1521690X0400020X.(2) Oosting, S F et al. “Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors.” Annals of oncology: official journal of the European Society for Medical Oncology vol. 21,1 (2010): 104-8. doi:10.1093/annonc/mdp265

scholarly journals Pure primary non-gestational choriocarcinoma originating in the ovary: A case report and literature review

Rare Tumors ◽  
2021 ◽  
Vol 13 ◽  
pp. 203636132110525
Author(s):  
Xiujie Yu ◽  
Qiuyue Du ◽  
Xiaojing Zhang ◽  
Yixin Liu ◽  
Yan Shen
Keyword(s):  
Germ Cell ◽  
Dna Analysis ◽  
Adnexal Mass ◽  
Elevated Serum ◽  
Germ Cell Tumors ◽  
Menstrual Disorders ◽  
Ki 67 ◽  
Gestational Choriocarcinoma ◽  
Β Hcg

Non-gestational choriocarcinoma (NGCO) of the ovary is rare, with a prevalence of less than 0.6% of all ovarian germ-cell tumors; and when found with other germ cell tumors, pure NGCO is exceedingly rare. We herein report the case of a 22-year-old woman who complained of menstrual disorders for over 2 months. MRI examination revealed an 11.4 cm right adnexal mass of the uterus, and the patients manifested an elevated serum level of β-hCG of 77,928 mIU/ml. Fertility-preserving surgery was performed, and the pathologic diagnosis was pure NGCO; immunohistochemical staining showed cancer cells that were positive for β-hCG, CK, hPL, SALL4, and Ki-67 (>80% of cells stained). We performed polymorphic DNA analysis and non-gestational origin was confirmed. The patient was then treated with six courses of chemotherapy with a BEP regimen, after which her serum β-hCG levels declined to normal levels, and she was free of disease at the 30-month follow-up.

Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ cell tumors: An Izmir Oncology Group (IZOG) study.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 476-476
Author(s):  
Tarik Salman ◽  
Elif Yildiz ◽  
Ibrahim Yildiz ◽  
Dilek Yavuzer ◽  
Mehtat Unlu ◽  
...  
Keyword(s):  
Lymph Node ◽  
Prognostic Factor ◽  
Germ Cell ◽  
Solid Phase ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Cd 117 ◽  
Preoperative Serum ◽  
Β Hcg

476 Background: Little progress has been made in the management of testicular germ cell tumors (TGCTs). c-kit (CD 117) is a good target for cancer treatment and possesses an impressive role in the current oncological practice. We aimed to evaluate c-kit expression in early stage TGCTs as a prognostic factor. Methods: Patients with TGCTs who were referred to the Medical Oncology Clinic were included in our study before starting chemotherapy. Immunohistochemistry was performed on formalin-fixed and paraffinembedded three-micrometer thick sections with CD 117 Rabbit Anti c-kit in vitro gene kit. Biochemically, we utilized AFP and β-HCG Immunlite 2000 device with solid phase chemiluminescent immunometric method, and LDH Roche models with the DP-standardized UV method. AFP 0-15 ng/ml, β-HCG < 0.1 mlu/ml and LDH 240-480 mg/dl were considered as normal values. Results: Sixty-five patients were included in our study. Forty-one (63%) patients had nonseminoma tumors (NSGCTs) and 24 (37%) had seminoma. Statistically significant c-kit expression was found in patients with seminoma (p<0.0001). There was no difference between negative or positive c-kit expression in terms of clinicopathological characteristics, including preoperative serum levels of AFP, β-HCG, LDH, lymph node involvement, distant metastasis, and IGCCCG risk classification. No correlation was found between these parameters and 5-year progression free survival (PFS) rate except for tumor stage, presence of lymph node metastasis and IGCCCG score (p=0.001, p=0.04, and p=0.0001, respectively). Five-year PFS rate of patients with positive CD 117 was 72.2% (95% CI, 54.6-89.8), and6.6% (95% CI, 31.2-82.1) for those without CD 117 expression involvement (p=0.12). Conclusions: So far, there has been no significant breakthrough in the treatment of cisplatinrefractory TGCTs in the era of targeted therapies. No prognostic importance of c-kit expression has been found in our study. However, we believe that c-kit expression, in numerical terms, can be considered as a good prognostic factor for patients with TGCTs. The fact that all seminoma cases displayed positive c-kit expression is what we think has driven this result.

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