title: Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients.
abstract: Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|National Cancer Center Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|National Cancer Center Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Bang Wool
authors.initials: BW
authors.lastname: Eom
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|National Cancer Center Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Myeong-Cherl
authors.initials: MC
authors.lastname: Kook
authors.affiliation: Department of Pathology, Inje University Ilsan Paik Hospital, Goyang, Korea.
authors.forename: Han-Seong
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Hai-Li
authors.initials: HL
authors.lastname: Hwang
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Vishal
authors.initials: V
authors.lastname: Chandra
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Shiv
authors.initials: S
authors.lastname: Poojan
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Yura
authors.identifier: http://orcid.org/0000-0002-1173-9172
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pathology, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Jae-Soo
authors.initials: JS
authors.lastname: Koh
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, and Samsung Biomedical Research Institute, Suwon, Korea.
authors.forename: Chang-Dae
authors.initials: CD
authors.lastname: Bae
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|National Cancer Center Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Jungsil
authors.initials: J
authors.lastname: Ro
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Kyeong-Man
authors.initials: KM
authors.lastname: Hong
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D049109:Cell Proliferation; D002945:Cisplatin / Q000627:therapeutic use; D003598:Cytoskeletal Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D013270:Stomach / Q000187:drug effects / Q000473:pathology*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C114988:CKAP2 protein, human; D003598:Cytoskeletal Proteins; D002945:Cisplatin