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ABSTRACT Objective: to evaluate the expression of the epithelial growth factor receptor (EGFR) by immunohistochemistry, and to verify its association with prognostic factors and survival of patients operated by cholangiocarcinoma. Methods: we verified the immunohistochemical expression of EGFR in 35 surgical specimens of cholangiocarcinoma (CCA). We obtained survival curves with the Kaplan-Meier method. Results: we found significant EGFR expression in ten (28.6%) of the 35 CCAs, eight with score 3 and two with score 2. Advanced stages (III and IV) presented higher EGFR expression (p=0.07). The clinical characteristics that were most associated with positive EGFR expression were female gender (p=0.06) and absence of comorbidities (p=0.06). Overall survival at 12, 24, 36 and 48 months was 100%, 82.5%, 59% and 44.2%, respectively. The survival of EGFR positive patients at 12, 24, 36 and 48 months was 100%, 75%, 50% and 0%, whereas for negative EGFR patients it was 100%, 87.5%, 65.6% and 65.6%, respectively. Conclusion: EGFR expression occurred in 28.6% of the cases studied and was associated with lower survival.

Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

The genetic and epigenetic alterations are being studied as one of the causes of gastric cancer (GC) progression and development. DNA methylation is an epigenetic alteration which leads to suppressor gene silencing and proto-oncogene activation, playing an important role in carcinogenesis. The histological types of gastric carcinoma have different genetic paths and the knowledge of the molecular bases of tumoral progression leads to diagnostic accuracy and attempted therapy. CDH1 (E-cadherin) and CDKN2A (p16(INK4A)) genes are thought to be tumoral suppressor genes and PTGS2 (COX-2) and genes are involved in tumour regulation and growth. In one hand, gene silencing as an epigenetic phenomenon, and in the other hand, gene expression enhancement due to possible demethylation, simultaneously, can facilitate carcinogénesis and tumoral progression. Our aim was to relate CDH1, p16(INK4A), COX-2 and EGFR genes DNA methylation with the several histological types of gastric carcinoma and chronic gastritis. We studied 55 formalin fixed paraffin embedded gastric biopsies: 35 were GC specimens (12 diffuse type, 15 intestinal type and 8 indeterminate type, according to Laurén's classification) and 20 samples had chronic gastritis (CG). The DNA was treated with sodium bisulfite after extraction and then performed Methylation Specific PCR (MSP). Statistical analysis was based on chi-square test and Exact Fisher's test. CpG island methylation was detected in 94% of the GC samples for CDH1, 91% for COX-2, 80% for p16(INK4A) and no methylation was detected in EGFR gene (0%). In CG, CpG island methylation was found in 100% for CDH1 and COX-2 genes, 90% for p16(INK4A) and 20% for EGFR. These results reveal significant differences in EGFR gene methylation distinguishing GC from CG (p < 0, 01), suggesting that gene demethylation leads to malignant transformation and favours the use of tyrosine-kinase inhibitors in its treatment. Genes COX2 e p16INK4A lower methylation in intestinal and diffuse types of GC, favours their different role in respective histogenesis.