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Contains fulltext : 225982.pdf (Publisher’s version ) (Open Access), BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Despite the use of multimodal treatment, survival of esophageal cancer (EC) patients remains poor. One proposed explanation for the relatively poor response to cytotoxic chemotherapy is intratumor heterogeneity. The aim was to establish a statistical model to objectively measure intratumor heterogeneity of the proportion of tumor (IHPoT) and to use this newly developed method to measure IHPoT in the pretreatment biopsies from from EC patients recruited to the OE02 trial. A statistical mixed effect model (

Background Gastric cancer (GC) is histologically a very heterogeneous disease, and the temporal development of diferent histological phenotypes remains unclear. Recent studies in lung and ovarian cancer suggest that KRAS activation (KRASact) can infuence histological phenotype. KRASact likely results from KRAS mutation (KRASmut) or KRAS amplifcation (KRASamp). The aim of the study was to investigate whether KRASmut and/or KRASamp are related to the histological phenotype in GC. Methods Digitized haematoxylin/eosin-stained slides from 1282 GC resection specimens were classifed according to Japanese Gastric Cancer Association (JGCA) and the Lauren classifcation by at least two observers. The relationship between KRAS status, predominant histological phenotype and clinicopathological variables was assessed. Results KRASmut and KRASamp were found in 68 (5%) and 47 (7%) GCs, respectively. Within the KRASmut and KRASamp cases, the most frequent GC histological phenotype was moderately diferentiated tubular 2 (tub2) type (KRASmut: n=27, 40%; KRASamp: n=21, 46%) or intestinal type (KRASmut: n=41, 61%; KRASamp: n=23, 50%). Comparing individual histological subtypes, mucinous carcinoma displayed the highest frequency of KRASmut (JGCA: n=6, 12%, p=0.012; Lauren: n=6, 12%, p=0.013), and KRASamp was more frequently found in poorly diferentiated solid type (n=12, 10%, p=0.267) or indeterminate type (n=12, 10%, p=0.480) GC. 724 GCs (57%) had intratumour morphological heterogeneity. Conclusions This is the largest GC study investigating KRAS status and histological phenotype. We identifed a relationship between KRASmut and mucinous phenotype. The high level of intratumour morphological heterogeneity could refect KRASmut heterogeneity, which may explain the failure of anti-EGFR therapy in GC.