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ALDH1 is an immunohistochemical diagnostic marker for solitary fibrous tumours and haemangiopericytomas of the meninges emerging from gene profiling study.

ABSTRACT: BACKGROUND: Solitary Fibrous Tumours (SFT) and haemangiopericytomas (HPC) are rare meningeal tumours that have to be distinguished from meningiomas and more rarely from synovial sarcomas. We recently found that ALDH1A1 was overexpressed in SFT and HPC as compared to soft tissue sarcomas. Using whole-genome DNA microarrays, we defined the gene expression profiles of 16 SFT/HPC (9 HPC and 7 SFT). Expression profiles were compared to publicly available expression profiles of additional SFT or HPC, meningiomas and synovial sarcomas. We also performed an immunohistochemical (IHC) study with anti-ALDH1 and anti-CD34 antibodies on Tissue Micro-Arrays including 38 SFT (25 meningeal and 13 extrameningeal), 55 meningeal haemangiopericytomas (24 grade II, 31 grade III), 163 meningiomas (86 grade I, 62 grade II, 15 grade III) and 98 genetically confirmed synovial sarcomas. RESULTS: ALDH1A1 gene was overexpressed in SFT/HPC, as compared to meningiomas and synovial sarcomas. These findings were confirmed at the protein level. 84% of the SFT and 85.4% of the HPC were positive with anti-ALDH1 antibody, while only 7.1% of synovial sarcomas and 1.2% of meningiomas showed consistent expression. Positivity was usually more diffuse in SFT/HPC compared to other tumours with more than 50% of tumour cells immunostained in 32% of SFT and 50.8% of HPC. ALDH1 was a sensitive and specific marker for the diagnosis of SFT (SE?=?84%, SP?=?98.8%) and HPC (SE?=?84.5%, SP?=?98.7%) of the meninges. In association with CD34, ALDH1 expression had a specificity and positive predictive value of 100%. CONCLUSION: We show that ALDH1, a stem cell marker, is an accurate diagnostic marker for SFT and HPC, which improves the diagnostic value of CD34. ALDH1 could also be a new therapeutic target for these tumours which are not sensitive to conventional chemotherapy.

SUBMITTER: Bouvier C

PROVIDER: S-EPMC3893364 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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ALDH1 is an immunohistochemical diagnostic marker for solitary fibrous tumours and haemangiopericytomas of the meninges emerging from gene profiling study.

Bouvier Corinne C Bertucci François F Métellus Philippe P Finetti Pascal P Maues de Paula André A Forest Fabien F Mokhtari Karima K Miquel Catherine C Birnbaum Daniel D Vasiljevic Alexandre A Jouvet Anne A Coindre Jean-Michel JM Loundou Anderson A Figarella-Branger Dominique D

Acta neuropathologica communications 20130509

<h4>Background</h4>Solitary Fibrous Tumours (SFT) and haemangiopericytomas (HPC) are rare meningeal tumours that have to be distinguished from meningiomas and more rarely from synovial sarcomas. We recently found that ALDH1A1 was overexpressed in SFT and HPC as compared to soft tissue sarcomas. Using whole-genome DNA microarrays, we defined the gene expression profiles of 16 SFT/HPC (9 HPC and 7 SFT). Expression profiles were compared to publicly available expression profiles of additional SFT o ...[more]

PMID: 24252471

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Project description:Solitary fibrous tumors (SFTs) are NAB2-STAT6 fusion-associated neoplasms. There are several subtypes of NAB2-STAT6 fusions, but their clinical significances are still unclear. Moreover, the mechanisms of malignant progression are also poorly understood. In this study, using 91 SFT cases, we examined whether fusion variants are associated with clinicopathological parameters and also investigated the molecular mechanism of malignant transformation using whole-exome sequencing. We detected variant 1b (NAB2ex4-STAT6ex2) in 51/91 (56%) cases and variants 2a/2b (NAB2ex6-STAT6ex16/17) in 17/91 (19%) cases. The NAB2-STAT6 fusion variant types were significantly associated with their primary site (P?<?0.001). In addition, a TERT promoter mutation was detected in 7/73 (10%) cases, and it showed a significant association with malignant SFTs (P?=?0.003). To identify molecular changes during malignant progression, we selected an index patient to obtain parallel tissue samples from the primary and metastatic tumors. In the metastatic tissue, 10 unique molecular alterations, including those in TP53 and APAF1, were detected. In vitro functional experiments showed that APAF1 depletion increased the tumor potency of cells expressing NAB2-STAT6 fusion protein under treatment with staurosporine. We found that TP53 immunopositivity (P?=?0.006) and loss of APAF1 immunoreactivity (P <?0.001) were significantly associated with malignant SFTs. Our study suggests that dysfunction of TP53 and APAF1 leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation. KEY MESSAGES: We firstly found that the TERT promoter mutation was strongly associated with malignant SFTs (P?=?0.003) and the representative 1b (NAB2ex4-STAT6ex2) or 2a (NAB2ex6-STAT6ex16) fusion variants similarly contribute to tumorigenicity. We also found that TP53 immunopositivity (P?=?0.006) and loss of APAF1 immunoreactivity (P?<?0.001) were significantly associated with malignant SFTs. Our study suggests that dysfunction of TP53 and APAF1 leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation.

Dataset Information

ALDH1 is an immunohistochemical diagnostic marker for solitary fibrous tumours and haemangiopericytomas of the meninges emerging from gene profiling study.

Publications

ALDH1 is an immunohistochemical diagnostic marker for solitary fibrous tumours and haemangiopericytomas of the meninges emerging from gene profiling study.

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