PMID- 27085557 OWN - NLM STAT- MEDLINE DCOM- 20170814 LR - 20201209 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 54 DP - 2016 Aug TI - High-resolution telomere fluorescence in situ hybridization reveals intriguing anomalies in germ cell tumors. PG - 106-12 LID - S0046-8177(16)30034-X [pii] LID - 10.1016/j.humpath.2016.03.015 [doi] AB - 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. CI - Copyright (c) 2016. Published by Elsevier Inc. FAU - Shekhani, Mohammed Talha AU - Shekhani MT AD - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Barber, John R AU - Barber JR AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Bezerra, Stephania M AU - Bezerra SM AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Heaphy, Christopher M AU - Heaphy CM AD - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Gonzalez Roibon, Nilda Diana AU - Gonzalez Roibon ND AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Taheri, Diana AU - Taheri D AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Reis, Leonardo O AU - Reis LO AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Guner, Gunes AU - Guner G AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Joshu, Corinne E AU - Joshu CE AD - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Netto, George J AU - Netto GJ AD - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Urology, James Buchanan Brady Urological Institute at Johns Hopkins, Baltimore, MD. FAU - Meeker, Alan K AU - Meeker AK AD - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Urology, James Buchanan Brady Urological Institute at Johns Hopkins, Baltimore, MD. Electronic address: Alan.meeker@gmail.com. LA - eng GR - R01 CA172380/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20160413 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Biomarkers, Tumor) RN - 0 (Co-Repressor Proteins) RN - 0 (DAXX protein, human) RN - 0 (Molecular Chaperones) RN - 0 (Nuclear Proteins) RN - 0 (Octamer Transcription Factor-3) RN - 0 (POU5F1 protein, human) RN - EC 3.6.4.- (DNA Helicases) RN - EC 3.6.4.12 (ATRX protein, human) RN - EC 3.6.4.12 (X-linked Nuclear Protein) RN - Nonseminomatous germ cell tumor RN - Testicular Germ Cell Tumor SB - IM MH - Adaptor Proteins, Signal Transducing/analysis MH - Adult MH - Biomarkers, Tumor/analysis/*genetics MH - Carcinoma in Situ/chemistry/*genetics/pathology/surgery MH - Co-Repressor Proteins MH - DNA Helicases/analysis MH - Fluorescent Antibody Technique MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Male MH - Molecular Chaperones MH - Neoplasms, Germ Cell and Embryonal/chemistry/*genetics/pathology/surgery MH - Nuclear Proteins/analysis MH - Octamer Transcription Factor-3/analysis MH - Seminoma/chemistry/*genetics/pathology/surgery MH - Telomere/chemistry/*genetics MH - Telomere Homeostasis MH - Telomere Shortening MH - Testicular Neoplasms/chemistry/*genetics/pathology/surgery MH - X-linked Nuclear Protein MH - Young Adult OTO - NOTNLM OT - Embryonal carcinoma OT - FISH, alternative lengthening of telomeres (ALT) OT - Germ cell neoplasia in situ (GCNIS) OT - Oct4 OT - Seminoma OT - Telomere OT - Testicular germ cell tumor (TGCT) EDAT- 2016/04/18 06:00 MHDA- 2017/08/15 06:00 CRDT- 2016/04/18 06:00 PHST- 2015/12/16 00:00 [received] PHST- 2016/03/23 00:00 [revised] PHST- 2016/03/31 00:00 [accepted] PHST- 2016/04/18 06:00 [entrez] PHST- 2016/04/18 06:00 [pubmed] PHST- 2017/08/15 06:00 [medline] AID - S0046-8177(16)30034-X [pii] AID - 10.1016/j.humpath.2016.03.015 [doi] PST - ppublish SO - Hum Pathol. 2016 Aug;54:106-12. doi: 10.1016/j.humpath.2016.03.015. Epub 2016 Apr 13.