Tae-In Park

Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers.

Introduction: Epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in the development and progression of lung cancer. We searched for mutations of EGFR pathway genes in non-small cell lung cancers (NSCLCs) and analyzed their relationship with clinicopathologic features. Methods: Mutations of EGFR, ERBB2, ERBB3, ERBB4, KRAS, NRAS, BRAF, PTEN, PIK3CA, LKB1, and AKT1 genes were determined by direct sequencing in 173 surgically resected NSCLCs—56 squamous cell carcinomas (SCCs) and 117 adenocarcinomas (ACs). Results: Of the 173 NSCLCs, a total of 65 mutations were detected in 63 (36.4%) tumors—10 (17.9%) in SCCs and 53 (45.3%) in ACs. Mutations in EGFR pathway genes were significantly more frequent in women and ACs than in women and SCCs (p = 0.02 and p < 0.001, respectively). The mutations occurred in a mutually exclusive pattern. When the genes were divided into three subgroups according to their roles in the signaling cascade, mutations in the EGFR/ERBB2 and KRAS/BRAF genes were more frequent in ACs than in SCCs (p < 0.001 and p = 0.01, respectively). In marked contrast, mutations in the PIK3CA/PTEN were more frequent in SCCs than in ACs (p = 0.002). Furthermore, mutations in the PIK3CA/PTEN genes were more frequent in smokers (p = 0.04). Discussion: Our study demonstrates that mutations in each part of the EGFR pathway were associated with different clinicopathologic features in patients with NSCLCs.

TP53 Mutations in Korean Patients with Non-small Cell Lung Cancer

Although TP53 mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, TP53 mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. TP53 mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, P<0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, P=0.01). Our study provides clinical and molecular characteristics of TP53 mutations in Korean patients with NSCLCs.

Lymphotoxin alfa and receptor-interacting protein kinase 1 gene polymorphisms may correlate with prognosis in patients with diffuse large B cell lymphoma treated with R-CHOP

PurposeDiffuse large B cell lymphoma (DLBCL) is a heterogenous disease entity due to diverse clinical outcomes to treatment. Most anticancer agents, regardless of their distinct mechanisms of action, ultimately kill cancer cells by inducing apoptosis. Accordingly, the present study analyzed the impact of polymorphisms of apoptosis-related genes on outcome in DLBCL patient treated with R-CHOP.Patients and methodsNinety patients with DLBCL treated with R-CHOP were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and 22 polymorphisms of 18 apoptosis-related genes were assessed using a polymerase chain reaction–restriction fragment length polymorphism assay.ResultsAll the evaluable patients were responsive to R-CHOP. The multivariate analysis showed that the AA genotype of lymphotoxin alpha (LTA) C804A (rs1041981) and GG genotype of RIPK1 G83A (rs2272990) were significantly correlated with a worse time to progression (TTP) compared with the combined C/A and C/C genotype and the combined G/A and A/A genotype (hazard ratio [HR]xa0=xa07.92; 95% confidence interval [CI]xa0=xa01.42–44.18; Pxa0=xa00.018 and HRxa0=xa020.02; 95% CIxa0=xa01.59–251.52; P valuexa0=xa00.018, respectively), whereas no association was observed between the other polymorphisms and TTP.ConclusionThe polymorphisms of LTA (rs1041981) and RIPK1 (rs2272990) may correlate with TTP in patients with DLBCL treated with R-CHOP.

Expression and Mutational Analysis of c-kit in Ovarian Surface Epithelial Tumors

Coexpression of Kit ligand and c-kit has been reported in some gynecologic tumors. To determine whether imatinib mesylate is useful in ovarian epithelial tumors, we performed immunohistochemical and mutational analysis. The cases consisted of 33 cases, which included 13 serous cystadenocarcinomas, 1 borderline serous tumor, 8 mucinous cystadenocarcinomas, 6 borderline mucinous tumors and 5 clear cell carcinomas. Five cases of serous cystadenoma and 5 cases of mucinous cystadenoma were also included. In the immunohistochemical study, 3 cases (3/6, 50%) of borderline mucinous cystic tumor and two cases (2/8, 25%) of mucinous cystadenocarcinoma show positive staining for KIT protein. Only one case (1/13, 7.7%) of serous cystadenocarcinoma had positive staining. On mutational analysis, no mutation was identified at exon 11. However, two cases of borderline mucinous tumors and one case of mucinous cystadenocarcinoma had mutations at exon 17. In these cases, the immunohistochemistry also shows focal positive staining at epithelial component. Although, KIT protein expression showed higher incidence in mucinous tumors than serous tumors, they lack KIT-activating mutations in exon 11. Thus, ovarian surface epithelial tumors are unlikely to respond to imatinib mesylate.

A Case of Venlafaxine-Induced Interstitial Lung Disease

A patient treated with venlafaxine for major depression developed an interstitial lung disease (ILD) with the characteristic clinical, radiological and pathological features of chronic hypersensitivity pneumonitis. A high resolution computed tomography scan demonstrated ground glass opacity, mosaic perfusion with air-trapping and traction bronchiectasis in both lungs. The pathological findings were consistent with a nonspecific interstitial pneumonia pattern. Clinical and radiological improvements were noted after the discontinuation of venlafaxine and the administration of a corticosteroid. This report provides further evidence that the anti-depressant venlafaxine can cause ILD.

Can Quantitative Volumetric Analysis Predict Tumor Recurrence in the Patients with Mucinous Adenocarcinoma of the Lung After Surgical Resection

RATIONALE AND OBJECTIVESnMucinous adenocarcinoma (MAC) is a distinct histologic variant subtype of lung adenocarcinomas. However, detailed radiologic findings and prognostic factors are still poorly understood. Thus, this study aimed to investigate the prognostic value of quantitative volumetric analysis of the computed tomography images of patients with MAC after. surgical resection.nnnMATERIALS AND METHODSnSemiautomatic segmentation from computed tomography images of 60 patients with pathologically confirmed MAC was performed and retrospectively reviewed. The main cutoff value in Hounsfield Units (HU) to predict tumor recurrence was defined by receiver-operating curve analysis. Solid volume of mass (SVM) was defined as the volume of HU greater than this cutoff, and solid ratio (Sratio) was defined as SVM divided by total volume. Each parameter was compared to clinicopathologic characteristics and maximum standardized uptake value. Disease-free survival (DFS) was assessed and was compared among patients. Univariate and multivariate Cox regression was performed to predict DFS of MAC.nnnRESULTSnThe cutoff value of HU as determined by ROC analysis was 20 HU. SVM and Sratio were positively correlated with the maximum standardized uptake and pathologic invasion size, respectively (p < 0.001). SVM and Sratio were significantly higher in the recurrence group than in the no-recurrence group (p < 0.001). Multivariate Cox proportional hazards regression analysis revealed that the SVM (Hazard Ratio 1.016; 95% Confidence Interval 1.000-1.032; pu202f=u202f0.048) and Sratio (Hazard Ratio 29.136; 95% Confidence Interval 1.419-598.191; pu202f=u202f0.029) were independent significant predictors of DFS.nnnCONCLUSIONnQuantitative volumetric parameters can predict the prognosis of patients with MAC after surgical resection.