June-Key Chung

Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas

Purpose: Epidermal growth factor receptor (EGFR) signalings have recently been implicated in the genesis and progression of cholangiocarcinomas. Thus, the EGFR kinase inhibitor appears to be promising in the treatment of this cancer. The response-predicting mutations in the tyrosine kinase domain of EGFR gene have recently been detected in non-small cell lung cancers. This study was, therefore, to investigate if these mutations are also found in cholangiocarcinomas. Methods: Twenty-two consecutive cholangiocarcinoma patients who underwent surgical resection were enrolled. Their resected paraffin-embedded cholangiocarcinoma specimens were used for mutation analysis, which was performed by DNA sequencing of exons 18, 19 and 21 in the EGFR gene. Clinical characteristics were compared between each group according to the presence or absence of mutations. Results: Three patients (13.6%) harbored EGFR mutations. All the mutations found were deletions in exon 19. Mutations were more common in intra-hepatic or poorly differentiated tumors. Differences in age, sex, stage at diagnosis and survival were not observed between mutation-positive and -negative patients. Conclusions: This study, for the first time, demonstrates that a subset of cholangiocarcinoma patients has response-predicting EGFR mutations. Therefore, a highly selected application of the EGFR kinase inhibitor would be therapeutically effective in these patients.

Infectious and Inflammatory Diseases

Positron emission tomography (PET) with fluorine-18-fluoro-2-deoxyD-glucose (FDG) is a powerful tool to diagnose, stage, and monitor cancer patients. While this technique exploits the fact that enhanced glucose utilization leading to high FDG uptake is characteristic for a variety of cancers, FDG is not a tumor-specific agent. Infectious or inflammatory lesions with high concentrations of activated leukocytes and/or macrophages also show significantly elevated levels of FDG accumulation. Such lesions can be mistaken for malignancy in patients undergoing PET studies for cancer evaluation, which may lead to false-positive interpretation. However, in patients with known or suspected infectious or inflammatory lesions, FDG-PET can be used to quantify the pathologic increase in glucose metabolism of inflammatory processes and may be a powerful clinical tool for the diagnosis of monitoring inflammatory activity. FDG-PET thus may be useful for evaluating such diseases caused by infections from a variety of bacteria, mycobacteria, virus, and fungi, and also infectious or inflammatory processes.