132P - Deciphering aggressive behavior in uterine inflammatory myofibroblastic tumors: Clinicopathological and molecular analysis

Background

Inflammatory myofibroblastic tumor (IMT) are rare mesenchymal neoplasms with uncertain behavior and wide anatomical distribution. Mostly driven by ALK fusions, uterine IMTs typically show benign behavior, but a subset exhibits aggression. Tumor size, mitotic activity, and other factors have been linked to aggressive outcomes, yet a precise predictive algorithm for IMT aggression is lacking.

Methods

A cohort of 9 uterine IMTs, 3 of which demonstrated aggressive behaviour, were evaluated for clinicopathologic variables. The cohort underwent DNA-targeted panel next-generation sequencing of 788 genes for mutation analysis, and panel RNA sequencing of 247 genes for detection of fusion genes and mRNA expression of selected genes. Immunohistochemical analysis of p53, p16 and ALK was performed. The results of all methods were compared among indolent and aggressive tumour.

Results

Expression of p16 was observed in five out of six indolent IMTs. One aggressive IMT exhibit aberrant p16 expression, and two cases showed a focal expression of 5%. All primary and recurrent tumours exhibited wild-type p53 expression and were ALK-positive. RNA sequencing revealed ALK rearrangement in all IMTs. Pathogenic mutations in MRE11 and PASK were detected exclusively in two indolent tumours, while APEX1 mutation was identified in one aggressive IMT. The aggressive IMTs demonstrated decreased expression of the AR, EGFR, SMARCA4, and SMARCB1 genes.

Conclusions

Our study emphasizes the need to integrate clinicopathological and molecular data for diagnosing uterine IMTs. Aggressive IMTs were larger, had higher mitotic activity, and occurred in older patients. Normal p16 expression does not exclude the possibility of aggressive behaviour in IMTs, and aberrant p16 expression predict aggressiveness only in a subset of IMTs. Our findings challenge prior research, showing pathogenic mutations aren’t restricted for aggressive IMTs. The SMARCB1 and SMARCA4 expression deregulation may affect IMT lesion aggressiveness. Further research is necessary to clarify the mechanisms driving aggressiveness in uterine IMTs.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

MZCR (AZV NU21-03-00122).

Disclosure

All authors have declared no conflicts of interest.