Abstract
Simple SummaryA solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise at any body location. Local or distant recurrences occur in a significant proportion of cases, but these recurrences are difficult to predict using clinical or pathological features. A specific genetic alteration, the gene fusion NAB2-STAT6, is considered to be the defining driver mutation, and different fusion variants seem to account for specific clinical and pathological features, but their prognostic value remains controversial. We inspected a series of 83 SFTs with a high rate of recurrence to evaluate the clinical significance of several potential biomarkers in addition to gene fusion. Our findings confirm previous observations and uncover novel associations of molecular alterations with clinical features, adding additional evidence for their potential application as molecular biomarkers that are helpful to predict the course of the disease.Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this entity has increased in recent years, new molecular alterations have emerged that could be helpful to refine current risk models. Here, we evaluated NAB2-STAT6 fusion variants and other molecular alterations in a series of 83 SFTs that are enriched in progressing cases. Gene fusion variants were identified by targeted RNA-seq in the whole series, whereas TERT promoter (pTERT) mutations were inspected by Sanger sequencing in a subset of 18 cases. Immunohistochemical assays were performed to assess BCOR and NTRK expression as well as P53 mutation status in 45, 44, and 44 cases, respectively. While confirming the associations of gene fusion variants with clinicopathological parameters, our results do not prove their prognostic value. Pan-TRK immunoexpresion correlated with recurrence/progression, P53 staining associated with higher mitotic counts, and pTERT mutations were enriched in cases with fatal outcome. An intriguing correlation was found for BCOR protein expression with gene fusion variants, size, and tumor location.
Highlights
Solitary fibrous tumors (SFT) represent a rare entity of soft tissue tumors of fibroblastic origin with intermediate malignant potential that can arise at any location of the body but are the most common in deep somatic soft tissue sand at body cavity sites [1,2]
The scoring system developed by Demicco and co-workers [4] has been validated in other independent studies and is widely used in the clinical setting [5]. This model is based on age, tumor size, mitotic count, and necrosis to predict the risk of metastasis, but it is accurate when considering different measures of patient outcome such as disease recurrence, which is the parameter used in other risk models [6,7]
In spite of using a series with advanced cases and long follow-up (GEIS cohort), we found no correlation of gene fusion variants with the final patient outcome nor did the signal transducer and activator of transcription 6 (STAT6)-FULL/transactivation domain (TAD) variants predict adverse clinical events when analysing a whole series enriched in advanced cases
Summary
Solitary fibrous tumors (SFT) represent a rare entity of soft tissue tumors of fibroblastic origin with intermediate malignant potential that can arise at any location of the body but are the most common in deep somatic soft tissue sand at body cavity sites (especially the pleura, pelvis, and retroperitoneum) [1,2]. SFTs have been traditionally classified into typical or malignant subtypes, this distinction does not necessarily correlate with clinical behavior In consequence, this concept is not referred to in the most recent WHO classification in order to avoid misleading identification of a typical subtype with a benign condition [2]. The scoring system developed by Demicco and co-workers (mDemicco) [4] has been validated in other independent studies and is widely used in the clinical setting [5] This model is based on age, tumor size, mitotic count, and necrosis to predict the risk of metastasis, but it is accurate when considering different measures of patient outcome such as disease recurrence, which is the parameter used in other risk models [6,7]. Homogeneous criteria for adverse outcome measure need to be stablished in order to make the performance assessment of different risk systems possible
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