Loss of ATRX/DAXX expression and alternative lengthening of telomeres in uterine leiomyomas
| Autor: | Maija E. A. Vahteristo, Ralf Bützow, Pernilla von Nandelstadh, Pia Vahteristo, Annukka Pasanen, Netta Mäkinen, Terhi Ahvenainen |
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| Přispěvatelé: | Genome-Scale Biology (GSB) Research Program, Research Programs Unit, University of Helsinki, Medicum, Department of Medical and Clinical Genetics, HUSLAB, Department of Pathology, Clinicum |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Leiomyosarcoma
0301 basic medicine Cancer Research Pathology Lung Neoplasms benign metastasizing leiomyoma FEATURES alternative lengthening of telomeres (ALT) Metastasis 0302 clinical medicine Medicine In Situ Hybridization Fluorescence Leiomyoma medicine.diagnostic_test Nuclear Proteins Middle Aged Telomere 3. Good health MED12 Gene Expression Regulation Neoplastic Oncology 030220 oncology & carcinogenesis Uterine Neoplasms Immunohistochemistry Female Co-Repressor Proteins Adult X-linked Nuclear Protein medicine.medical_specialty 3122 Cancers Malignancy uterine leiomyosarcoma Diagnosis Differential 03 medical and health sciences Death-associated protein 6 alpha-thalassemia/mental retardation syndrome X-linked (ATRX) death domain-associated protein (DAXX) Humans ATRX Adaptor Proteins Signal Transducing uterine leiomyoma business.industry Telomere Homeostasis medicine.disease Survival Analysis 030104 developmental biology business Gene Deletion Molecular Chaperones Fluorescence in situ hybridization |
| ISSN: | 4650-4656 |
| Popis: | Background Uterine leiomyomas (ULs) are the most common gynecologic tumors and affect 3 of every 4 women by the age of 50 years. The majority of ULs are classified as conventional tumors, whereas 10% represent various histopathological subtypes with features that mimic malignancy. These subtypes include cellular and mitotically active ULs and ULs with bizarre nuclei. Uterine leiomyosarcoma (ULMS), the malignant counterpart of UL, is an aggressive cancer with poor overall survival. The early diagnosis and preoperative differentiation of ULMS from UL are often challenging because their symptoms and morphology resemble one another. Recent studies have shown frequent loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) or death domain-associated protein (DAXX) expression in ULMS, and this is often associated with an alternative lengthening of telomeres (ALT) phenotype. Methods To investigate ATRX and DAXX expression and the presence of ALT in UL subtypes, immunohistochemical and telomere-specific fluorescence in situ hybridization analyses were performed. The study material consisted of 142 formalin-fixed, paraffin-embedded tissue samples representing various UL subtypes and 64 conventional ULs. Results A loss of ATRX or DAXX and/or ALT was detected in 6.3% of the histopathological UL subtype samples (9 of 142). Two patients whose ULs showed either ATRX loss or ALT were later diagnosed with a pulmonary smooth muscle tumor. Pulmonary tumors displayed molecular alterations found in the corresponding uterine tumors, which indicated metastasis to the lungs. All conventional ULs displayed normal ATRX, DAXX, and telomeres. Conclusions These results highlight the differences between conventional and histopathologically atypical ULs and indicate that some UL subtype tumors may harbor long-term malignant potential. Cancer 2018;124:4650-4656. (C) 2018 American Cancer Society. |
| Databáze: | OpenAIRE |
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