Follow-Up Imaging of Inflammatory Myofibroblastic Tumor of the Uterus and Its Spontaneous Regression

Inflammatory myofibroblastic tumor (IMT) is an aggressive benign mass that may arise from various tissues and organs with a great variability of histological and clinical appearances. Due to variable and nonspecific imaging findings, diagnosis of IMT is not obtained before surgery. The aim of this paper is to present CT and MRI findings during four-year follow-up of complete, spontaneous regression of IMT of the uterus. The diagnosis was made by histology and immunohistochemistry analysis of the open excisional biopsy specimen. At that time, the organ of origin was not specified. After analysis of the follow-up imaging findings and the mode of tumor regression, the uterus was proclaimed as the probable site of origin. IMT of the uterus is extremely rare and has been reported in ten cases up to now. The gradual, complete regression of uterine IMT documented by CT and MRI may contribute to understanding of its nature

Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer

Background: Radiation therapy is an indispensable part of various treatment modalities for breast cancer. Specifically, for non-inflammatory locally advanced breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently indicated as a second line therapy in the event of lack of response to neoadjuvant chemotherapy. Still approximately one third of patients fails to respond favourably to pRT. The aim of this study was to explore molecular mechanisms underlying differential response to radiotherapy (RT) to identify predictive biomarkers and potential targets for increasing radiosensitivity.Methods: The study was based on a cohort of 134 LABC patients, treated at the Institute of Oncology and Radiology of Serbia (IORS) with pRT, without previous or concomitant systemic therapy. Baseline transcriptional profiles were established using Agilent 60 K microarray platform in a subset of 23 formalin-fixed paraffin-embedded (FFPE) LABC tumour samples of which 11 radiotherapy naïve and 3 post-radiotherapy samples passed quality control and were used for downstream analysis. Biological networks and signalling pathways underlying differential response to RT were identified using Ingenuity Pathways Analysis software. Predictive value of candidate genes in the preoperative setting was further validated by qRT-PCR in an independent subset of 60 LABC samples of which 42 had sufficient quality for data analysis, and in postoperative setting using microarray data from 344 node-negative breast cancer patients (Erasmus cohort, GSE2034 and GSE5327) treated either with surgery only (20%) or surgery with RT (80%).Results: We identified 192 significantly differentially expressed genes (FDR < 0.10) between pRT-responsive and non-responsive tumours, related to regulation of cellular development, growth and proliferation, cell cycle control of chromosomal replication, glucose metabolism and NAD biosynthesis II route. APOA1, MAP3K4, and MMP14 genes were differentially expressed (FDR < 0.20) between pRT responders and non-responders in preoperative setting, while MAP3K4 was further validated as RT-specific predictive biomarker of distant metastasis free survival (HR = 2.54, [95%CI:1.42–4.55], p = 0.002) in the postoperative setting.Conclusions: This study pinpoints MAP3K4 as a putative biomarker of response to RT in both preoperative and postoperative settings and a potential target for radiosensitising combination therapy, warranting further pre-clinical studies and prospective clinical validation