title: In Epstein-Barr virus-associated gastric carcinoma a high density of CD66b-positive tumor-associated neutrophils is associated with intestinal-type histology and low frequency of lymph node metastasis.
abstract: Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is characterized by prominent intratumoral lymphocyte infiltration, with some infiltration by other types of inflammatory cells, such as neutrophils. In this study, the significance of tumor-associated neutrophils (TANs) and cytotoxic T lymphocytes (CTLs) was investigated in EBVaGC. CD66b-positive TANs and CD8-positive CTLs in surgically resected EBVaGC tissues were evaluated by immunohistochemistry and digital imaging analysis. Cut-off values were determined with receiver operating characteristic curve analyses. Forty-two of 77 cases (55 %) had some infiltration of TANs (CD66b-positive areas >0.5 %, TAN(+)) and 35 (45 %) had scant infiltration (TAN(-)). Thirty-five cases (45 %) had more CTLs (CD8-positive area >18 %, CTL-high) and 42 (55 %) had fewer (CTL-low). There was no correlation between CD66b- and CD8-positive areas in the tumor (P = 0.453). TAN(+) correlated with intestinal-type histology (P = 0.048) and low frequency of lymph node metastasis (P = 0.023), while CTL-low with upper location (P = 0.030) and advanced invasion depth (pT2 or greater) (P = 0.006). Disease-specific survival was not significantly correlated with TANs or CTLs. Multivariate logistic regression analysis revealed TAN(-) to be independently associated with lymph node metastasis (P = 0.036). None of the cases of TAN(+) early EBVaGC with submucosal invasion showed lymph node metastasis (95 % confidence interval 0-13.3 %). When compared with 24 EBV-negative gastric carcinomas, EBVaGC had significantly more CTLs (P < 0.001), while there was no difference in the number of TANs. TANs in EBVaGC may suppress lymph node metastasis, and absence of TANs might suggest careful follow-up or additional therapy in cases of post-endoscopic resection.
authors.affiliation: Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Tokyo, 113-0033, Japan.
authors.forename: Ruri
authors.initials: R
authors.lastname: Saito
authors.affiliation: Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Seto
authors.affiliation: Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan. mfukayama-tky@umin.org.|Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Tokyo, 113-0033, Japan. mfukayama-tky@umin.org.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis*; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D013274:Stomach Neoplasms / Q000473:pathology* / Q000821:virology
keywords: Epstein–Barr virus; Gastric carcinoma; Lymph node metastasis; Lymphocytes; Neutrophils