Min A Kim

EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number

Aims:u2002 Epidermal growth factor receptor (EGFR) expression has been observed in a variety of solid tumours with the potential of new targeted therapeutic agents. The aim was to evaluate the EGFR status of gastric carcinoma (GC) using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma

Aims:u2002 Epithelial–mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers. The aim was to evaluate the expression of EMT‐related proteins in gastric carcinoma (GC).

Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker

BackgroundThe objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU), folinic acid and oxaliplatin (modified FOLFOX-6) in patients with advanced gastric cancer (AGC), as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin.MethodsSeventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m2). Genomic DNA from the patients peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC.ResultsThe overall response rate (RR) was 43.8%. Median time to progression (TTP) and overall survival (OS) were 6.0 months and 12.6 months, respectively. Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6 bp/-6 bp) in TS-3UTR (55.0% vs. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, p = 0.034), and C/A or A/A in XPD156 (52.0% vs. 26.1% in C/C, p = 0.038). The -6 bp/-6 bp in TS-3UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, p = 0.032).ConclusionModified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.

Clinicopathologic and protein expression differences between cardia carcinoma and noncardia carcinoma of the stomach

Although the incidence of adenocarcinoma of the stomach has decreased over the past several decades, gastric cardia carcinoma has increased over the same period.

Comparative analysis of protein expressions in primary and metastatic gastric carcinomas

Because metastatic cancers are derived from their primary counterparts, their molecular profiles could reasonably be expected to be similar to those of primary cancers. However, this expectation has been proven to be untrue in several human cancers. To explore protein expressional differences in primary and metastatic gastric carcinoma, we evaluated the expressions of 32 tumor-associated proteins in 250 pairs of primary and metastatic gastric carcinoma tissues by immunohistochemistry using tissue array slides. In metastatic gastric carcinomas, the expressions of epidermal growth factor receptor, c-erbB2, and trefoil factor 1(TFF-1) were higher and those of beta-catenin, E-cadherin, fragile histone triad gene (FHIT), glutathione S transferase-pi (GST-pi), kangai 1 (KAI1), and nuclear factor-kappaB (NF-kappaB) were lower than in primary gastric carcinomas. Furthermore, the expressions of beta-catenin, E-cadherin, KAI1, and NF-kappaB were associated with an advanced T and combined stage. In addition, the loss of E-cadherin expression during lymph node metastasis or E-cadherin immunonegativity in metastatic lesions and epidermal growth factor receptor expression in primary gastric carcinomas were independently associated with a poor prognosis by multivariate analysis. In conclusion, the expression of some tumor-associated proteins and their prognostic significance in metastatic gastric carcinomas differ from those in primary tumors. Consequently, analysis of both metastatic gastric carcinomas and their primary counterparts may be required to fully determine the molecular characteristics of node-positive gastric carcinoma.

Mucinous gastric carcinomas: clinicopathologic and molecular analyses.

Mucinous gastric carcinoma (MGC) is characterized by substantial mucous lakes within tumors and comprises 3% of gastric carcinomas at the authors institute.

Prognostic significance of loss of c-fos protein in gastric carcinoma

Abstractc-fos was first identified as a viral oncoprotein, and has been studied in terms of its oncogenic function in tumorigenesis. Many experimental and clinical data indicated that c-fos expression plays a role in the progression of several types of carcinomas. However, some recent studies challenge this view as they indicate that c-fos has tumor suppressor activity. In the present study, we assessed c-fos protein expression in 625 consecutive gastric cancers immunohistochemically, and analyzed its relationship with clinicopathologic factors and survival. We found that a loss of c-fos expression is correlated with a more advanced stage, lymph node metastasis, lymphatic invasion and shorter survival, indicating that c-fos expression in gastric cancer cells is lost during progression and that this loss is associated with a poor prognosis. The above findings suggest that loss of c-fos expression has tumor suppressor activity in gastric cancer and we suspect that this suppressor activity might be related to the pro-apoptotic function of c-fos.

Epidermal growth factor receptor intron 1 CA dinucleotide repeat polymorphism and survival of advanced gastric cancer patients treated with cetuximab plus modified FOLFOX6

(Cancer Sci 2010; 101: 793–799)

Metastasis-Associated Protein S100A4 and p53 Predict Relapse in Curatively Resected Stage III and IV (M0) Gastric Cancer

Purpose: Pathologic stage is the most important predictive factor of relapse in gastric cancer after curative resection. However, patients with the same stage often have different risks of relapse. Here, we investigated whether the expressions of molecular markers can supplement the current staging system in terms of relapse prediction. Patients and Methods: One hundred and nine stage III or IV (M0) patients who had received curative gastrectomy followed by adjuvant 5-fluorouracil and cisplatin chemotherapy were included in this study. The expressions of molecular markers including p53, p27, COX-2, HER-2, EGFR, maspin, S100A4, E-cadherin, Sp1, and p97 were analyzed by immunohistochemistry in cancer and paired normal tissues. Results: The overall relapse rate was 58.7%, and pathologic stage was a significant predictive factor of relapse (42% in stage IIIA, 48% in IIIB, 76% in IV, p = 0.005). Of the 10 markers examined, p53 and S100A4 were expressed only in tumor tissues, and S100A4 expression was significantly associated with a higher relapse rate (85% vs. 53%, p = 0.008). In multivariate analysis including tumor stage, S100A4 and p53 expression were independent predictive factors of relapse (relative risk, 6.98; 95% confidence interval [CI], 1.608-30.342, 3.49; 95% CI, 1.328-9.186, respectively). On comparing patients who expressed S100A4 or p53 with those who expressed neither, relapse rates were 58% vs. 25% in stage III (p = 0.011) and 95% vs. 59% in stage IV (M0) (p = 0.003). Conclusion: In addition to staging system, the expressions of S100A4 and p53 were significant predictive factors of relapse in gastric cancer after curative resection and adjuvant chemotherapy.

Low Ki‐67 proliferation index is an indicator of poor prognosis in gastric cancer

We designed this study to assess the biologic significance of Ki‐67 proliferation index (PI) in gastric cancer.