Clinicopathological correlations of mesenteric fibrosis and evaluation of a novel biomarker for fibrosis detection in small bowel neuroendocrine neoplasms

Abstract

Purpose Mesenteric fibrosis (MF) in small intestinal neuroendocrine neoplasms (SINENs) is often associated with significant morbidity and mortality. The detection of MF is usually based on radiological criteria, but no previous studies have attempted a prospective, multidimensional assessment of mesenteric desmoplasia to determine the accuracy of radiological measurements. There is also a lack of non-invasive biomarkers for the detection of image-negative MF. Methods A multidimensional assessment of MF incorporating radiological, surgical and histological parameters was performed in a prospective cohort of 34 patients with SINENs who underwent primary resection. Pre-operative blood samples were collected in 20 cases to evaluate a set of five profibrotic circulating transcripts-the "fibrosome"-that is included as an "omic" component of the NETest. Results There was a significant correlation between radiological and surgical assessments of MF (p < 0.05). However, there were several cases of image-negative MF. The NETest-fibrosome demonstrated an accuracy of 100% for the detection of microscopic MF. Conclusions The detection of MF by radiological criteria has limitations. The NETest-fibrosome is a promising biomarker for fibrosis detection and further validation of these results would be needed in larger, multicentre studies.

Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review

“…Notably, when utilizing histopathological, surgical and radiological correlations, computed tomography (CT) imaging has limitations and may underestimate the presence of MF [ 80 , 81 ]. This needs to be considered when making clinical decisions regarding the management of these patients in view of the considerable morbidity associated with MF.…”

“…However, these markers perform modestly and have not been specifically applied in the clinical practice for the assessment of MF as yet. Recently, a set of five profibrotic circulating transcripts with known roles in fibrosis (CTGF, CD59, amyloid precursor-like protein 2 (APLP2), frizzled homologue (FZD) 7 and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L)), taking the name of “fibrosome” has been assessed [ 81 ]. The combination of these five circulating transcripts (from the entire 51-gene molecular signature of the NETest) has demonstrated an accuracy of 100% for the detection of microscopic MF and a higher accuracy, as compared to radiological and surgical assessments.…”

“…The combination of these five circulating transcripts (from the entire 51-gene molecular signature of the NETest) has demonstrated an accuracy of 100% for the detection of microscopic MF and a higher accuracy, as compared to radiological and surgical assessments. Given the ability of the multianalyte NETest to act as a liquid biopsy that can capture the multidimensionality of NEN, the “fibrosome” set appears to be a promising biomarker for MF detection [ 81 ]. However, further validation of these results is warranted in prospective studies.…”

Evaluation of circulating transcript analysis (NETest) in small intestinal neuroendocrine neoplasms after surgical resection

“…Second, a monoanalyte measurement is, by definition, unidimensional and does not capture the diverse biological processes of a tumour cell that a multigene assay measures. Thus, in comparison to monoanalyte measurements, the transcriptomebased NETest is a multianalyte (51 genes) biomarker that has shown promising results and is more reliable in diagnosis and defining NEN disease status [27][28][29][30][31][32].…”

Transcriptomic Profiling of In Vitro Tumor-Stromal Cell Paracrine Crosstalk Identifies Involvement of the Integrin Signaling Pathway in the Pathogenesis of Mesenteric Fibrosis in Human Small Intestinal Neuroendocrine Neoplasms

“…A multidimensional assessment of mesenteric fibrosis was used to classify patients into different groups of mesenteric fibrosis severity. The classification incorporates surgical, radiological ( 6 ), and histological ( 21 , 22 ) parameters and provides an accurate classification of mesenteric fibrosis as we have previously described ( 23 ). Using this more precise, multidimensional evaluation of mesenteric fibrosis (see Supplementary File 2 ) we were able to classify patients into four groups: non-fibrotic, minimally fibrotic (only histological evidence of fibrosis), and mildly or severely fibrotic (depending on the amount of macroscopic fibrosis).…”