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High-resolution telomere fluorescence in situ hybridization reveals intriguing anomalies in germ cell tumors.
- Source :
-
Human pathology [Hum Pathol] 2016 Aug; Vol. 54, pp. 106-12. Date of Electronic Publication: 2016 Apr 13. - Publication Year :
- 2016
-
Abstract
- Testicular germ cell tumor (TGCT) is the most common malignancy of young men. Most patients are completely cured, which distinguishes these from most other malignancies. Orchiectomy specimens (n=76) were evaluated using high-resolution (single-cell discriminative) telomere-specific fluorescence in situ hybridization (FISH) with simultaneous Oct4 immunofluorescence to describe telomere length phenotype in TGCT neoplastic cells. For the first time, the TGCT precursor lesion, germ cell neoplasia in situ (GCNIS) is also evaluated in depth. The intensity of the signals from cancerous cells was compared to the same patient's reference cells-namely, healthy germ cells (defined as "medium" length) and interstitial/somatic cells (defined as "short" telomere length). We observed short telomeres in most GCNIS and pure seminomas (P=.006 and P=.0005, respectively). In contrast, nonseminomas displayed longer telomeres. Lesion-specific telomere lengths were documented in mixed tumor cases. Embryonal carcinoma (EC) demonstrated the longest telomeres. A fraction of EC displays the telomerase-independent alternative lengthening of telomeres (ALT) phenotype (24% of cases). Loss of ATRX or DAXX nuclear expression was strongly associated with ALT; however, nuclear expression of both proteins was retained in half of ALT-positive ECs. The particular distribution of telomere lengths among TGCT and GCNIS precursors implicate telomeres anomalies in pathogenesis. These results may advise management decisions as well.<br /> (Copyright © 2016. Published by Elsevier Inc.)
- Subjects :
- Adaptor Proteins, Signal Transducing analysis
Adult
Biomarkers, Tumor analysis
Carcinoma in Situ chemistry
Carcinoma in Situ pathology
Carcinoma in Situ surgery
Co-Repressor Proteins
DNA Helicases analysis
Fluorescent Antibody Technique
Humans
Male
Molecular Chaperones
Neoplasms, Germ Cell and Embryonal chemistry
Neoplasms, Germ Cell and Embryonal pathology
Neoplasms, Germ Cell and Embryonal surgery
Nuclear Proteins analysis
Octamer Transcription Factor-3 analysis
Seminoma chemistry
Seminoma pathology
Seminoma surgery
Telomere chemistry
Telomere Homeostasis
Telomere Shortening
Testicular Neoplasms chemistry
Testicular Neoplasms pathology
Testicular Neoplasms surgery
X-linked Nuclear Protein
Young Adult
Biomarkers, Tumor genetics
Carcinoma in Situ genetics
In Situ Hybridization, Fluorescence
Neoplasms, Germ Cell and Embryonal genetics
Seminoma genetics
Telomere genetics
Testicular Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-8392
- Volume :
- 54
- Database :
- MEDLINE
- Journal :
- Human pathology
- Publication Type :
- Academic Journal
- Accession number :
- 27085557
- Full Text :
- https://doi.org/10.1016/j.humpath.2016.03.015