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Abstract Background Rash, liver dysfunction, and diarrhea are known major adverse events associated with erlotinib and gefitinib. However, clinical trials with gefitinib have reported different proportions of adverse events compared to trials with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown to be involved in the metabolism of gefitinib but not erlotinib. It has been hypothesized that CYP2D6 phenotypes may be implicated in different adverse events associated with gefitinib and erlotinib therapies. Methods The frequency of each adverse event was evaluated during the period in which the patients received gefitinib or erlotinib therapy. CYP2D6 phenotypes were determined by analysis of CYP2D6 genotypes using real-time polymerase chain reaction techniques, which can detect single-nucleotide polymorphisms. The CYP2D6 phenotypes were categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of the adverse events associated with each factor, including CYP2D6 activities and treatment types. Results A total of 232 patients received gefitinib therapy, and 86 received erlotinib therapy. Reduced function of CYP2D6 was associated with an increased risk of rash of grade 2 or more (OR, 0.44; 95% confidence interval [CI], 0.21–0.94; *p = 0.03), but not diarrhea ≥ grade 2 (OR, 0.49; 95% CI, 0.17–1.51; *p = 0.20) or liver dysfunction ≥ grade 2 (OR, 1.08; 95% CI, 0.52–2.34; *p = 0.84) in the gefitinib cohort. No associations were observed between any adverse events in the erlotinib cohort and CYP2D6 phenotypes (rash: OR, 1.77; 95% CI, 0.54–6.41; *p = 0.35/diarrhea: OR, 1.08; 95% CI, 0.21–7.43; *p = 0.93/liver dysfunction: OR, 0.93; 95% CI, 0.20–5.07; *p = 0.93). Conclusions The frequency of rash was significantly higher in patients with reduced CYP2D6 activity who treated with gefitinib compared to patients with functional CYP2D6. CYP2D6 phenotypes are a risk factor for the development of rash in response to gefitinib therapy.

Background: Computed tomography (CT)-guided needle biopsy is a well-established and dependable procedure for the diagnosis of pulmonary lesions. Some tissue biopsy samples have loose cohesion and disintegrate into tiny pieces before formalin fixation. The purpose of this study was to assess the association between the fresh macroscopic appearance of samples obtained using CT-guided needle biopsy and the clinicopathological features of non-small cell lung cancer (NSCLC)., Methods: A total of 111 patients who underwent CT-guided lung needle biopsy at Osaka City University Hospital between May 2009 and May 2013 were enrolled. Macroscopic appearance was categorized as either loose or tight cohesion. Samples were evaluated using Azan staining to detect collagen fibers. The staining intensity was multiplied by the percentage of positive cells, and the specimen was categorized as having either low (<100) or high expression ( ≥100). Univariate and multivariate logistic regression models were used to evaluate significant covariates for tumor metastasis., Results: In the cohort of 111 patients, the diagnostic rates in loose and tight cohesions were 82.6% and 87.5%, respectively (p=0.509). In 60 patients diagnosed with NSCLC, Azan staining of collagen fibers was positive in 93.5% of the samples with tight cohesion and 28.6% of the samples with loose cohesion (p<0.001). In the multivariate logistic regression models, distant metastasis was significantly associated with loose cohesion (p=0.026)., Conclusions: These results suggest that the macroscopic appearance of CT-guided biopsy samples correlates with tumor metastasis in NSCLC.

Background: In vitro studies have indicated that epidermal growth factor receptor (EGFR) may intensify signaling output by the receptor's overexpression, heterodimerization with HER-2, or autocrine expression of ligands. The purpose of the present study was to evaluate the correlation between EGFR and its related proteins and to explore the prognostic value of the proteins., Materials and Methods: Immunohistochemical staining of transforming growth factor alpha (TGF-alpha), EGFR, HER-2, and phosphorylated (p-)Akt was performed in specimens surgically excised from 91 consecutive patients with p-stage I non-small cell lung cancer (NSCLC). Expression or coexpression of TGF-alpha and the receptors were related to expression of p-Akt. The prognostic impact of these peptides was also tested., Results: TGF-alpha, EGFR and HER-2 overexpressions were detected in 32%, 79% and 13% of tumors, respectively. Coexpressions of TGF-alpha & EGFR and EGFR & HER-2 were observed in 29% and 11% of tumors, respectively. P-Akt expression was found in 73% of tumors. Significant correlations between EGFR TGF-alpha or coexpression of TGF-alpha & EGFR and p-Akt expression were found (p=0.006, 0.008 and 0.010, respectively). No proteins examined had an impact on relapse-free survival., Conclusion: The Akt pathway is frequently involved in NSCLC and overexpression of EGFR and autocrine expression of TGF-alpha may increase the potency of Akt activation.