Cetuximab, an immunoglobulin G1 chimeric monoclonal antibody directed against the epidermal growth factor receptor, is currently considered to be the strategy with the most potential for the treatment of gastric cancer due to the low frequency of KRAS mutations in patients with gastric cancer. However, the therapeutic success of cetuximab in colorectal cancer (CRC) has demonstrated that the clinical effect of cetuximab is closely dependent not only on KRAS mutations, but also BRAF and phosphoinositide-3-kinase, catalytic, α polypeptide (PIK3CA) mutations. In the present study, the status of KRAS, BRAF and PIK3CA mutations in gastric cancer were investigated concomitantly in order to aid the selection of patients eligible for treatment with cetuximab. Mutations in KRAS (exon 2), BRAF (exon 15) and PIK3CA (exon 9 and exon 20) were retrospectively evaluated by high resolution melting analysis and DNA direct sequencing in samples from 156 patients with gastric cancer. Mutations in either KRAS or PIK3CA were identified in 13 samples (8.3%), 7 samples with KRAS mutations and 6 samples with PIK3CA mutations. No mutations in the BRAF gene were identified. The frequency of mutations in either KRAS or PIK3CA were significantly higher in patients without lymph node metastasis than those with. Furthermore, KRAS and PIK3CA mutations were mutually exclusive. The present study, therefore, suggested that it may be necessary to evaluate KRAS and PIK3CA mutations concomitantly for the selection of patients eligible for treatment with cetuximab.

Mismatch repair (MMR) plays a pivotal role in keeping the genome stable. MMR dysfunction can lead to carcinogenesis by gene mutation accumulation. HMSH2 and hMLH1 are two key components of MMR. High or low expression of them often mark the status of MMR function. Mutations (EGFR, KRAS, etc) are common in non-small cell lung cancer (NSCLC). However, it is not clear what role MMR plays in NSCLC gene mutations. The expression of MMR proteins hMSH2 and hMLH1, and the proliferation markers PCNA and Ki67 were measured by immunohistochemistry in 181 NSCLCs. EGFR and KRAS mutations were identified by high resolution melting analysis. Stronger hMLH1 expression correlated to a higher frequency of EGFR mutations in exon 19 and 21 (p<0.0005). Overexpression of hMLH1 and the adenocarcinoma subtype were both independent factors that related to EGFR mutations in NSCLCs (p=0.013 and p<0.0005). The expression of hMLH1, hMSH2 and PCNA increased, while Ki67 expression significantly decreased (p=0.030) in NSCLCs with EGFR mutations. Overexpression of hMLH1 could be a new molecular marker to predict the response to EGFR-TKIs in NSCLCs. Furthermore, EGFR mutations might be an early event of NSCLC that occur before MMR dysfunction.

PurposeTraditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However, the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it is necessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditional chemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR).Materials and MethodsThe expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry, and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2) were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergo traditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expression of P-gp and LRP and mutations in EGFR and KRAS.ResultsThe expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients; the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutations was significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequency of EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancers that did not express P-gp or LRP.ConclusionNSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.

Background. The prognosis for gliomas is still dismal when treated with traditional approaches. Molecular targeted therapy has become a trend in treating tumors, including gliomas. However, molecular characteristics vary among different kinds of tumors and ethnic groups. Objectives. The aim of the research was to study the expression characteristics of key components in the EGFR pathway of gliomas in order to contribute new data for the molecular targeted treatment of gliomas. Material and Methods. EGFR, KRAS, BRAF, PI3K, phospho-EGFR and Ki67 expression were detected with immunohistochemistry in 82 glioma specimens. Results. The expression of EGFR was positively correlated with the patients' age. There were no significant differences in clinicopathological characteristics between gliomas with and without phospho-EGFR expression. EGFR overexpression was significantly correlated with phospho-EGFR expression. In gliomas with EGFR activation, overexpressions of EGFR, BRAF and PI3K were significantly correlated with proliferation. However, in gliomas without phospho-EGFR expression, only BRAF overexpression was significantly related to the proliferation of tumor cells. Conclusions. BRAF overexpression could be an independent factor causing tumorigenesis in gliomas regardless of phospho-EGFR expression. The molecular characteristics can vary with the increasing age of glioma patients (Adv Clin Exp Med 2014, 23, 6, 893-899).

Objective: To determine whether a subgroup of gastric cancer patients might benefit from epidermal growth factor receptor-tyrosine kinase inhibitors. Methods: A total of 103 gastric cancer samples were collected for this study. High-resolution melting and deoxyribonucleic acid sequencing were used to detect epidermal growth factor receptor mutations in exons 19 and 21. Results: Polymerase chain reaction-high-resolution melting was successfully performed on all 103 samples. Aberrant melting curves were found in only one sample. Sanger sequencing revealed a 15 bp deletion (c.2235_2249del; p.Glu746_Ala750del) in epidermal growth factor receptor exon 19. The sample was from a male patient, and the pathological diagnosis was a mucin-producing gastric cancer with lymph node metastasis. To date, this is the first report on epidermal growth factor receptor exon 19 mutation in gastric cancer. Conclusions: An epidermal growth factor receptor mutation in exon 19 was identified in mucinproducing gastric cancer sample from a male patient. This mutation indicates that the small subgroup of patients with mucin-producing gastric cancer might benefit from epidermal growth factor receptor-tyrosine kinase inhibitors.