ABSTRACT
AIM: To investigate human epidermal growth factor receptor 2 (HER2) amplification and protein expression in mixed gastric carcinoma. METHODS: Fluorescence in situ hybridization and immunohistochemistry were used to detect HER2 amplification and protein expression in 277 cases of mixed gastric carcinoma. Protein staining intensity was rate as 1+, 2+, or 3+. RESULTS: Of the 277 cases, 114 (41.2%) expressed HER2 protein. HER2 3+ staining was observed in 28/277 (10.1%) cases, 2+ in 37/277 (13.4%) cases, and 1+ in 49/277 (17.7%) cases. A HER2 amplification rate of 17% was detected, of which 25/28 (89.3%) were observed in the HER2 3+ staining group, 17/37 (45.9%) in 2+, and 5/49 (10.2%) in 1+. Of the 47 patients with HER2 amplification who received chemotherapy plus trastuzumab, 22 demonstrated median progression-free and overall survivals of 9.1 mo and 16.7 mo, respectively, which were significantly better than those achieved with chemotherapy alone (5.6 mo and 12.1 mo, respectively) in 19 previously treated patients (Ps < 0.05). CONCLUSION: HER2 detection in mixed gastric carcinoma displays high heterogeneity. Relatively quantitative parameters are needed for assessing the level of HER2 amplification and protein expression.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma/chemistry , Neoplasms, Complex and Mixed/chemistry , Receptor, ErbB-2/analysis , Stomach Neoplasms/chemistry , Adult , Aged , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/genetics , Carcinoma/drug therapy , Carcinoma/genetics , Carcinoma/mortality , Carcinoma/pathology , Disease Progression , Disease-Free Survival , Female , Gene Amplification , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Middle Aged , Neoplasms, Complex and Mixed/drug therapy , Neoplasms, Complex and Mixed/genetics , Neoplasms, Complex and Mixed/mortality , Neoplasms, Complex and Mixed/pathology , Patient Selection , Predictive Value of Tests , RNA, Messenger/analysis , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Time Factors , Trastuzumab/therapeutic use , Treatment OutcomeABSTRACT
Esophageal squamous cell carcinoma (ESCC) is one of the most common primary malignant tumor of digestive tract. However, the early diagnosis and molecular mechanisms that underlie tumor formation and progression have been progressed less. To identify new biomarkers for ESCC, we performed a comparative proteomic research. Isobaric tags for relative and absolute quantitation-based proteomic method was used to screen biomarkers between ESCC and normal. 802 non-redundant proteins were identified, 39 of which were differentially expressed with 1.5-fold difference (29 up-regulated and 10 down-regulated). Through Swiss-Prot and GO database, the location and function of differential proteins were analyzed, which are related to the biological processes of binding, cell structure, signal transduction, cell adhesion, etc. Among the differentially expressed proteins, TP-alpha, collagen alpha-1(VI) chain and S100A9 were verified to be upregulated in 77.19%, 75.44% and 59.65% of ESCC by immunohistochemistry and western-blot. Diagnostic value of these three proteins was validated. These results provide new insights into ESCC biology and potential diagnostic and therapeutic biomarkers, which suggest that TP-alpha, collagen alpha-1(VI) chain and S100A9 are potential biomarkers of ESCC, and may play an important role in tumorigenesis and development of ESCC.
Subject(s)
Calgranulin B/blood , Carcinoma, Squamous Cell/metabolism , Collagen Type VI/blood , Esophageal Neoplasms/metabolism , Multienzyme Complexes/blood , Proteomics/methods , Adult , Biomarkers, Tumor/metabolism , Blotting, Western , Calgranulin B/biosynthesis , Child , Child, Preschool , Collagen Type VI/biosynthesis , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , Middle Aged , Mitochondrial Trifunctional Protein , Multienzyme Complexes/biosynthesis , Sensitivity and Specificity , Up-RegulationABSTRACT
OBJECTIVE: To clone novel gene from suppression subtraction library established for screening down-regulated genes in gastric carcinoma, and the effects of novel gene on gastric tumorigenicity were analyzed. METHODS: Sequencing results of 860 positive colonies chosen randomly were compared by Blast program in GenBank. Novel gene fragment was amplified by rapid amplification of cDNA ends (RACE). The mRNA expression of novel gene was detected by Northern blot and semi-quantitative PCR in 25 cases of gastric carcinoma tissue and counterpart normal gastric mucosa. The structure and chromosomal location of novel gene were investigated by Bio-message technique. RESULTS: A 233 bp novel gene fragment was screened out from 860 clones and a 802 bp novel gene was obtained by RACE. The novel gene was named as GDDM, registered in the number of AF494508 by GenBank. The mRNA expression of GDDM in gastric carcinoma tissue (4.496+/-0.637) was significantly lower than that in the counterpart normal gastric mucosa (36.919+/-6.290)(P<0.01). Chromosomal location of GDDM gene was at 4q31. CONCLUSION: The cloned novel gene, GDDM, is down-regulated in gastric carcinoma, and it is likely to be involved in gastric tumorigenicity.
