Intratumoral morphological heterogeneity can be an indicator of genetic heterogeneity in colorectal cancer.

Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with RAS wild-type. However, resistance to targeted therapy is often observed and can be primary or acquired. One reason for primary resistance is the presence of mutations that are undetected due to genetic heterogeneity, which can be expressed by differences present in primary tumor and distant metastasis or recurrence or by an intratumoral heterogeneity (presence of different subclones in the investigated tumor sample). The aim of our study was to investigate if morphological heterogeneity can be an indicator of intratumoral heterogeneity. We analysed 13 samples with homogeneous and six samples with heterogeneous morphology with NGS. We were able to demonstrate that intratumoral genetic heterogeneity is present in all studied tumor samples, independent of homogeneous or heterogeneous morphology. Moreover, one sample of our cohort with morphological and genetic heterogeneity had a genetic wild-type profile in one tumor component. Therefore, we recommend to include each morphologically identifiable tumor component in the mutational analysis to not overlook resistance-inducing or potentially targetable mutations.

Follow-Up Comparison of Fluorescence Optical Imaging With Musculoskeletal Ultrasound for Early Detection of Psoriatic Arthritis.

Objectives: Early diagnosis of psoriatic arthritis (PsA) is crucial for a patient outcome but hampered by heterogenous manifestation and a lack of specific biomarkers. We recently showed that fluorescence optical imaging (FOI) can differentiate between patients with confirmed and suspected PsA. This study aims to follow-up (FU) patients with confirmed and suspected PsA focusing on patients with a change from suspected to confirmed PsA by the use of FOI in comparison with musculoskeletal ultrasound (MSUS). Methods: Follow-up examination of patients included in the study performed by Erdmann-Keding et al. in which FOI of both hands was performed in a standardized manner using three predefined phases (p1-p3) and PrimaVista Mode (PVM). The comparison was drawn to grayscale-power Doppler (GS/PD) MSUS of the clinically dominant hand (wrist, MCP, PIP, DIP 2-5) from dorsal or palmar. Results: Patients with a change from suspected to diagnosed PsA showed an increased prevalence of joints with pathological enhancement in FOI (p = 0.046) with an unchanged joint distribution pattern, especially with a dominant involvement of DIP joints. Compared to the baseline, these patients were three times more common to show enhancement in FOI p3 at FU. Newly detected pathologic joints by FOI (PVM, p2) and MSUS at FU were positively associated with the change of diagnosis from suspected to confirmed PsA (FOI: AUC 0.78; GSUS: AUC 0.77). Conclusion: Fluorescence optical imaging appears to be a helpful tool to detect early PsA and to distinguish between acute and chronic disease stages. It could thereby become a suitable tool as a screening method to select psoriasis patients with an indication for further rheumatological evaluation.

Influence of mucinous and necrotic tissue in colorectal cancer samples on KRAS mutation analysis.

Evaluation of the RAS mutation status is necessary for patients with advanced colorectal cancer to predict the response to anti-EGFR therapy. In routine diagnostics, FFPE tissue samples are tested by sequencing (amplicon-based NGS and Sanger) to obtain the RAS status of the patient. Samples that are collected after chemotherapy occasionally contain necrotic tissue. Furthermore, colorectal cancer tissue sometimes has mucinous components. This may pose a challenge to molecular analysis because mucinous tumor samples often contain only few tumor cells compared to solid tumor samples. Therefore, the aim of this study was to explore if mucin or necrosis affect mutation analysis and if mucinous tumor samples contain enough tumor cells for reliable mutation detection. To this end, we analyzed KRAS status in 10 samples showing mucin production and 10 samples with necrosis. In all 20 samples the tissue areas with the highest amount of mucin or necrosis were used for re-evaluation. These results show no differences with those obtained during routine diagnostics, where analysis of mucinous or necrotic areas was tried to avoid. Our study thus shows that mucin and necrosis have no influence on KRAS mutation analysis. Furthermore we were able to demonstrate that mucinous adenocarcinoma contains enough tumor cells for a valid mutation analysis. In addition, we also observed only minor differences in KRAS status results when comparing Sanger sequencing with NGS. Both methods detected the KRAS mutation in 19 of 20 tested samples, even for mutated samples with low allele-frequencies.