Prognostic Value of Alternative Lengthening of Telomeres–Associated Biomarkers in Uterine Sarcoma and Uterine Carcinosarcoma

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Abstract

Objective

A subset of cancer cells maintains telomere lengths in a telomerase-independent manner known as the alternative lengthening of telomeres (ALT). The goal of this study was to evaluate the frequency of ALT in uterine sarcoma and carcinosarcoma and to assess its association with clinical parameters.

Methods

Retrospectively collected paraffin blocks from 41 patients with uterine sarcomas and carcinosarcomas were analyzed for ALT-associated promyelocytic leukemia bodies (APBs), which are a significant feature of ALT cells, using combined immunofluorescence and telomere fluorescence in situ hybridization. In addition, a C-circle assay and human telomerase reverse transcriptase immunohistochemistry were performed to support these results.

Results

The APB assay and C-circle assay indicated that 46.3% (19/41 cases) and 36.4% (8/22 cases) of sarcomas of the uterus, respectively, were positive for ALT. Alternative lengthening of telomerase positivity was correlated with high-grade uterine sarcoma and parameters indicative of an aggressive tumor, such as tumor size (P = 0.033) and mitotic index (P = 0.001); ALT positivity was negatively correlated with human telomerase reverse transcriptase reactivity (P = 0.036). In a survival analysis, the presence of APBs was found to be a poor prognostic factor for disease-free survival (P = 0.018) and overall survival (P = 0.021).

Conclusions

Alternative lengthening of telomeres is a prevalent mechanism in uterine sarcomas and carcinosarcomas and is associated with the aggressiveness of the tumor and tumor progression. Importantly, ALT positivity is an indicator of poor prognosis for patients with uterine sarcoma and carcinosarcoma.

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