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Aims Insulinoma‐associated protein 1 (INSM1) is a transcription factor that is expressed in developing and mature neuroendocrine tissue. Recent studies have shown that INSM1 is a sensitive marker for neuroendocrine tumours. The aims of this study were to evaluate INSM1 expression in primary gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) and in their known metastases, in order to assess its sensitivity as compared with chromogranin‐A (CgA) and synaptophysin (SYN), and to evaluate any change in expression between primary and metastatic disease. Methods and results We identified 30 patients with primary GEP‐NEN. Liver metastatic tissue was available for 26 patients; two patients had two metachronous metastatic foci, yielding a total of 28 metastatic cases. An additional two and seven non‐paired cases of primary and metastatic grade 3 GEP‐NEN, respectively, were included. To assess specificity, we evaluated the expression of these markers in other primary tumours (colorectal adenocarcinoma, acinar cell carcinoma, solid pseudopapillary neoplasm, cholangiocarcinoma, and hepatocellular carcinoma) and metastatic tumours in the liver (adrenal cortical, breast and prostate carcinomas) that may present as differential diagnoses. In our cohort, all of the primary GEP‐NENs and 94% of the metastatic GEP‐NENs expressed INSM1. INSM1 showed similar sensitivity to SYN and higher sensitivity than CgA in both primary and metastatic neoplasms. INSM1 has comparable specificity to CgA, and higher specificity than SYN. Conclusions The nuclear reactivity and the high sensitivity and specificity of INSM1 make it a preferred neuroendocrine marker. In conclusion, INSM1 can be used as a single first‐line marker for primary and metastatic GEP‐NEN.

INTRODUCTION:Urgency, the immediate need to defecate, is common in active ulcerative colitis (UC). We investigated the association of urgency in patients with UC with (i) quality of life (QoL) domains and (ii) future hospitalizations, corticosteroid use, and colectomy for UC.METHODS:We conducted a cross-sectional and subsequent longitudinal study within Inflammatory Bowel Disease Partners, a patient-powered research network. We described associations of levels of urgency in patients with UC with Patient-Reported Outcomes Measurement Information System QoL domains. We conducted a longitudinal cohort to determine associations between baseline urgency and subsequent hospitalization, corticosteroid use, or colectomy for UC within 12 months. We used bivariate statistics and logistic regression models to describe independent associations.RESULTS:A total of 632 patients with UC were included in the cross-sectional study. After adjusting for clinical variables, rectal bleeding, and stool frequency, urgency defined as “hurry,” “immediately,” and “incontinence” increased the odds of social impairment (odds ratio [OR] 2.05 95% confidence interval [CI] 1.24–3.4, OR 2.76 95% CI 1.1–6.74, and OR 7.7 95% CI 1.66–38.3, respectively) compared with “no hurry.” Urgency also significantly increased the odds of depression, anxiety, and fatigue. Urgency was associated with a significant increase in risk of hospitalizations and corticosteroids, whereas “hurry,” “immediately,” and “incontinence” increased the odds of colectomy within 12 months by 1.42 (1.15–1.75), 1.90 (1.45–2.50), and 3.69 (2.35–5.80).DISCUSSION:We demonstrated that urgency is a patient-reported outcome independently associated with compromised QoL and future risk of hospitalizations, corticosteroids, and colectomy. Our findings support the consideration of urgency as a UC-specific patient-reported outcome and its use as an outcome in clinical trials to capture QoL and risk of clinical decompensation.

Reg4 is highly expressed in gastrointestinal malignancies and acts as a mitogenic and pro-invasive factor. Our recent works suggest that Reg4 binds with CD44 and induces its proteolytic cleavage to release intra-cytoplasmic domain of CD44 (CD44ICD). The goal of this study is to demonstrate clinical significance of the Reg4-CD44/CD44ICD pathway in stage II/III colon cancer and its association with clinical parameters of aggression. We constructed a tissue microarray (TMA) of 93 stage II/III matched colon adenocarcinoma patients, 23 with recurrent disease. The TMA was immunohistochemically stained for Reg4, CD44, and CD44ICD proteins and analyzed to identify associations with tumor characteristics, recurrence and overall survival. The TMA data analysis showed a significant correlation between Reg4 and CD44 (r 2 = 0.23, P = 0.028), CD44 and CD44ICD (r 2 = 0.36, p = 0.0004), and Reg4 and CD44ICD (r 2 = 0.45, p ≤ 0.0001). Reg4 expression was associated with larger tumor size (r 2 = 0.23, p = 0.026). Although, no association was observed between Reg4, CD44, or CD44ICD expression and disease recurrence, Reg4-positive patients had a median survival of 4 years vs. 7 years for Reg4-negative patients (p = 0.04) in patients who recurred. Inhibition of the Reg4-CD44/CD44ICD pathway may be a future therapeutic target for colon cancer patients.

Summary Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8 weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.