RESUMEN
BACKGROUND: To evaluate quantitative iodine parameters from the arterial phase dual-energy computed tomography (DECT) scans as an imaging biomarker for tumor grade (TG), mitotic index (MI), and Ki-67 proliferation index of hepatic metastases from neuroendocrine tumors (NETs) of the gastrointestinal (GI) tract. Imaging biomarkers have the potential to provide relevant clinical information about pathologic processes beyond lesion morphology. NETs are a group of rare, heterogeneous neoplasms classified by World Health Organization (WHO) TG, which is derived from MI and Ki-67 proliferation index. Imaging biomarkers for these pathologic features and TG may be useful. METHODS: Between January 2014 and April 2019, 73 unique patients with hepatic metastases from NET of the GI tract underwent DECT of the abdomen with an arterial phase were analyzed after exclusions. Using GSIViewer software (GE Healthcare, Madison, Wisconsin), elliptical regions of interest (ROIs) were placed over selected hepatic metastases by a fellowship trained abdominal radiologist. Quantitative iodine concentration (IC) data was extracted from the lesion ROIs, and the normalized IC (lesion IC/aorta IC) and relative IC (lesion IC/liver IC) for each liver were calculated. Spearman correlation was calculated for lesion mean IC, normalized IC, and relative IC to both Ki-67 proliferation and mitotic indices. Student's t-test was performed to compare lesion mean IC, normalized IC and relative IC between WHO TGs. RESULTS: There was very weak correlation between both normalized IC and relative IC for both Ki-67 proliferation and mitotic indices. A significant difference was not observed between normalized IC and relative IC to distinguish metastases from G1 and G2/3 tumors. CONCLUSIONS: Our study finds limited potential for quantitative parameters from DECT to distinguish neuroendocrine hepatic metastases by WHO TG, as well as limited potential as an imaging biomarker for Ki-67 proliferation and mitotic indices in this setting. Our findings of a lack of correlation between Ki-67 and quantitative iodine parameters stands in contrast to existing literature that reports positive correlations for these parameters in the rectum and stomach.
RESUMEN
OBJECTIVE: Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. DESIGN: We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤ 50 years old (n=188), a group of sporadic CRC >50 years (MSS n=89; MSI n=46), and a group of Lynch syndrome CRCs (n=20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. RESULTS: Mean LINE-1 methylation levels (± SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥ 65% LINE-1 methylation had significantly better overall survival (p=0.026, log rank test). CONCLUSIONS: LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.