Publication: The pathobiological behaviors and prognosis associated with Japanese gastric adenocarcinomas of pure WHO histological subtypes
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Date
2010
Authors
Zheng, Hua-Chuan ; Zheng, Yu-shuang ; Xia, Pu ; Xu, Xiao-yan ; Xing, Ya-nan ; Takahashi, Hiroyuki ; Guan, Yi-Fu ; Takano, Yasuo
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Japan is a high-risk region for gastric
carcinoma with a comparatively early stage and
favorable prognosis. To clarify the pathobiological
behaviors and prognosis of Japanese gastric
adenocarcinoma, we analyzed the clinicopathological
characteristics of different WHO subtypes of
carcinomas. The expression of ki-67, CPP32, p53, FHIT,
maspin, parafibromin, GRP78, GRP94, EMMPRIN,
VEGF, P-GSK3ß-ser9, fascin, cortactin, Arp2, Arp3
MUC-2, MUC-5AC and MUC-6 was examined using
immunohistochemistry and tissue microarrays. The
majority of cases were well-, poorly-, or moderatelydifferentiated
subtype, whereas the minority were
papillary or signet ring cell carcinoma (SRC). Patients
with poorly-differentiated or SRC carcinoma were
predominantly young and female. Poorly-differentiated
and mucinous carcinomas were larger, with deeper
invasion, more venous or lymphatic invasion, frequent
lymph node involvement and peritoneal dissemination,
or higher staging. The SRC group exhibited weaker
expression of ki-67, CPP32, p53, parafibromin, GRP78,
GRP94, P-GSK3ß-ser9, VEGF or cortactin. The
moderately-differentiated subtype exhibited lower
expression of FHIT and Arp3 positivity. The poorlydifferentiated
group showed weaker expression of
CPP32, EMMPRIN, MUC-2, MUC-5AC, and MUC-6.
Survival analysis indicated that the patients with poorlydifferentiated
or mucinous subtypes had a lower
cumulative survival rate than those with papillary, well-,
moderately-differentiated, or SRC carcinomas (P<0.05).
The age, invasive depth, lymphatic invasion, peritoneal dissemination, and WHO classification were
independent prognostic factors for carcinoma patients
(P<0.05). It was suggested that poorly-differentiated and
mucinous subtypes are more aggressive and of
unfavorable prognosis among Japanese gastric
carcinomas. Lower levels of proliferation and apoptosis,
as well as alterations in tumor suppressor genes, mucin
production and ER stress protein played important roles
in the pathogenesis of poorly-differentiated and SRC
carcinomas.
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