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Differential nuclear ATRX expression in sarcomas.

Christian Koelsche^1,2, Marcus Renner³, Pascal Johann^4,5

¹Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.

|August 21, 2015

Summary

This summary is machine-generated.

Nuclear ATRX loss is common in high-grade sarcomas and strongly linked to alternative lengthening of telomeres (ALT), particularly with complete ATRX loss.

Keywords:

ALT ATRX immunohistochemistry sarcomas telomeres

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Area of Science:

Oncology
Genetics
Pathology

Background:

Nuclear ATRX loss is observed in various cancers.
Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism.
A link between ATRX loss and ALT has been noted in some malignancies.

Purpose of the Study:

To investigate the correlation between nuclear ATRX expression and ALT in a large cohort of sarcomas.
To determine the prevalence of ATRX loss in different sarcoma subtypes.

Main Methods:

Immunohistochemistry was used to assess nuclear ATRX expression in 573 sarcomas.
Telomere-specific fluorescence in-situ hybridization (FISH) was employed to detect the ALT phenotype in 50 sarcomas with ATRX loss.
Sarcomas were categorized by entity, grade, and ATRX expression pattern.

Main Results:

Complete nuclear ATRX loss was found in 58 of 573 high-grade sarcomas, most frequently in undifferentiated pleomorphic sarcomas and pleomorphic liposarcomas.
Heterogeneous ATRX expression was observed in an additional 20 sarcomas.
ALT was present in 41 of 42 sarcomas with complete ATRX loss, but only in 2 of 8 with heterogeneous expression.

Conclusions:

Complete or heterogeneous nuclear ATRX loss occurs in a significant proportion of high-grade sarcomas.
A causal relationship between ATRX loss and ALT is suggested, especially in cases with complete ATRX loss.