TY - JOUR
T1 - Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer
T2 - results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer
AU - Kerckhoffs, K. G. P.
AU - Liu, D. H. W.
AU - Saragoni, L.
AU - van der Post, R. S.
AU - Langer, R.
AU - Bencivenga, M.
AU - Iglesias, M.
AU - Gallo, G.
AU - Hewitt, L. C.
AU - Fazzi, G. E.
AU - Vos, A. M.
AU - Renaud, F.
AU - Yoshikawa, T.
AU - Oshima, T.
AU - Tomezzoli, A.
AU - de Manzoni, G.
AU - Arai, T.
AU - Kushima, R.
AU - Carneiro, F.
AU - Grabsch, H.
N1 - Funding Information:
KGP Kerckhoffs and DHW Liu would like to thank the British Division of the International Academy of Pathology for the travel grant and the third poster price of the Leeds Pathology 2019 meeting in Harrogate.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - Gastric cancer
KW - Signet-ring cells
KW - Mucin
KW - Histological phenotype
KW - Survival
KW - LYMPH-NODE METASTASIS
KW - HUMAN STOMACH CANCERS
KW - PROGNOSTIC-SIGNIFICANCE
KW - CLINICOPATHOLOGICAL PARAMETERS
KW - ESOPHAGOGASTRIC JUNCTION
KW - PHENOTYPIC-EXPRESSION
KW - UNITED-STATES
KW - NORMAL MUCOSA
KW - BETA-CATENIN
KW - CARCINOMA
U2 - 10.1007/s10120-020-01086-0
DO - 10.1007/s10120-020-01086-0
M3 - (Systematic) Review article
C2 - 32488651
SN - 1436-3291
VL - 23
SP - 765
EP - 779
JO - Gastric Cancer
JF - Gastric Cancer
IS - 5
ER -