Exp Mol Med.  2015 Nov;47(11):e193. 10.1038/emm.2015.79.

Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients

• Kim YW
• Eom BW
• Kook MC
• Kim HS
• Kim MK
• Hwang HL
• Chandra V
• Poojan S
• Song Y
• Koh JS
• Bae CD
• Ro J
• Hong KM

• KMID: 2359880
• DOI: http://doi.org/10.1038/emm.2015.79

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.

MeSH Terms

Aged
Antineoplastic Agents/therapeutic use
Biomarkers, Tumor/analysis
Cell Proliferation
Cisplatin/therapeutic use
Cytoskeletal Proteins/*analysis
Female
Humans
Immunohistochemistry
Male
Middle Aged
Multivariate Analysis
Prognosis
Proportional Hazards Models
Stomach/drug effects/*pathology
Stomach Neoplasms/diagnosis/drug therapy/*pathology
Survival Analysis
Antineoplastic Agents
Biomarkers, Tumor
Cisplatin
Cytoskeletal Proteins