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1.
Article | WPRIM | ID: wpr-836251

ABSTRACT

Microscopic polyangiitis (MPA) is a small vessel vasculitides mostly associated with anti-neutrophil cytoplasmic antibodies (ANCA). The kidney is the most commonly affected organ in MPA. We report the case of a 9-year-old girl with ANCA-negative MPA who initially presented with respiratory symptoms, including cough, sputum, and dyspnea. Based on her symptoms, atypical pneumonia was suspected. Also, childhood interstitial lung disease was considered based on findings seen on chest CT. Despite initial improvement of symptoms with oral corticosteroid therapy, dyspnea with initiation of corticosteroid tapering was noted. A final diagnosis of MPA was made after lung biopsy. ANCA was negative in both the initial and repeat blood tests. Oral cyclophosphamide and prednisolone treatments led to full remission. Since then, the patient has been treated with low dose prednisolone and azathioprine for maintenance. A good treatment response was achieved and her clinical symptoms, pulmonary functions, and radiologic findings have since improved. Thus, early and precise diagnosis of MPA is crucial for remission induction and prevention of symptom relapse.

2.
Cancer Research and Treatment ; : 1120-1134, 2020.
Article | WPRIM | ID: wpr-831140

ABSTRACT

Purpose@#Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD) @*Materials and Methods@#We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing. @*Results@#Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions. @*Conclusion@#Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.

3.
Cancer Research and Treatment ; : 1540-1548, 2019.
Article in English | WPRIM | ID: wpr-763207

ABSTRACT

PURPOSE: Lung cancers presenting as subsolid nodule commonly have peripheral location, making the cancer-pleura relationship noteworthy. We aimed to evaluate the effect of pleural attachment and/or indentation on visceral pleural invasion (VPI) and recurrence-free survival. MATERIALS AND METHODS: Patients who underwent curative resection of lung cancer as subsolid nodules from April 2007 to January 2016 were retrospectively evaluated. They were divided into four groups according to their relationship with the pleura. Clinical, radiographical, and pathological findings were analyzed. RESULTS: Among 404 patients with malignant subsolid nodule, 120 (29.7%) had neither pleural attachment nor indentation, 26 (6.4%) had attachment only, 117 (29.0%) had indentation only, and 141 (34.9%) had both. VPI was observed in nodules of 36 patients (8.9%), but absent in nonsolid nodules and in those without pleural attachment and/or indentation. Compared to subsolid nodules with concurrent pleural attachment and indentation, those with attachment only (odds ratio, 0.12; 95% confidence interval [CI], 0.02 to 0.98) and indentation only (odds ratio, 0.10; 95% CI, 0.03 to 0.31) revealed lower odds of VPI. On subgroup analysis, the size of the solid portion was associated with VPI among those with pleural attachment and indentation (p=0.021). Such high-risk features for VPI were associated with earlier lung cancer recurrence (adjusted hazard ratio, 3.31; 95% CI, 1.58 to 6.91). CONCLUSION: Concurrent pleural attachment and indentation are risk factors for VPI, and the odds increase with larger solid portion in subsolid nodules. Considering the risk of recurrence, early surgical resection could be encouraged in these patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Humans , Lung Neoplasms , Lung , Neoplasm Invasiveness , Pleura , Prognosis , Recurrence , Retrospective Studies , Risk Factors
4.
Cancer Research and Treatment ; : 1086-1097, 2019.
Article in English | WPRIM | ID: wpr-763171

ABSTRACT

PURPOSE: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. MATERIALS AND METHODS: We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. RESULTS: The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. CONCLUSION: Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Drug Therapy , Humans , Immunohistochemistry , Neoadjuvant Therapy , Platinum , Prognosis , Retrospective Studies
5.
Article in English | WPRIM | ID: wpr-766033

ABSTRACT

Blockade of the programmed cell death-1 (PD-1) axis has already been established as an effective treatment of non-small cell lung cancer. Immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) protein is the only available biomarker that can guide treatment with immune checkpoint inhibitors in non-small cell lung cancer. Because each PD-1/PD-L1 blockade was approved together with a specific PD-L1 IHC assay used in the clinical trials, pathologists have been challenged with performing various assays with a limited sample. To provide a more unified understanding of this, several cross-validation studies between platforms have been performed and showed consistent results. However, the interchangeability of assays may be limited in practice because of the risk of misclassification of patients for the treatment. Furthermore, several issues, including the temporal and spatial heterogeneity of PD-L1 expression in the tumor, and the potential for cytology specimens to be used as an alternative to tissue samples for PD-L1 testing, have still not been resolved. In the future, one of the main aims of immunotherapy research should be to find a novel predictive biomarker for PD-1 blockade therapy and a way to combine it with PD-L1 IHC and other tests.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Humans , Immunohistochemistry , Immunotherapy , Population Characteristics
6.
Article in English | WPRIM | ID: wpr-766014

ABSTRACT

BACKGROUND: Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression. METHODS: HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed. RESULTS: HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501). CONCLUSIONS: Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.


Subject(s)
Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Humans , Immunohistochemistry , Leukocytes , Lung , Multivariate Analysis , Neoplasm Metastasis , Prognosis
7.
Yonsei Medical Journal ; : 202-210, 2018.
Article in English | WPRIM | ID: wpr-713102

ABSTRACT

PURPOSE: Previous retrospective studies suggest that anaplastic lymphoma kinase (ALK) mutation-positive (ALK+) non-small cell lung cancer (NSCLC) patients are sensitive to pemetrexed. To determine its efficacy, we retrospectively evaluated clinical outcomes of pemetrexed-based chemotherapy in patients with ALK+ NSCLC. MATERIALS AND METHODS: We identified 126 patients with advanced, ALK+ NSCLC who received first-line cytotoxic chemotherapy. We compared response, progression-free survival (PFS), and overall survival (OS) rates according to chemotherapy regimens. Furthermore, we evaluated intracranial time to tumor progression (TTP) and proportion of ALK+ cells as prognostic factors. RESULTS: Forty-eight patients received pemetrexed-based chemotherapy, while 78 received other regimens as first-line treatment. The pemetrexed-based chemotherapy group showed superior overall response (44.7% vs. 14.3%, p < 0.001) and disease control (85.1% vs. 62.3%, p=0.008) rates. The pemetrexed-based chemotherapy group also exhibited longer PFS (6.6 months vs. 3.8 months, p < 0.001); OS rates were not significantly different. The lack of exposure to second-generation ALK inhibitors and intracranial metastasis on initial diagnosis were independent negative prognostic factors of OS. Intracranial TTP was similar between the treatment groups (32.7 months vs. 35.7 months, p=0.733). Patients who harbored a greater number of ALK+ tumor cells (≥70%) showed prolonged OS on univariate analysis (not reached vs. 44.8 months, p=0.041), but not on multivariate analysis (hazard ratio: 0.19, 95% confidence interval: 0.03–1.42; p=0.106). CONCLUSION: Pemetrexed-based regimens may prolong PFS in patients with ALK+ NSCLC as a first-line treatment, but are not associated with prolonged OS. Exposure to second-generation ALK inhibitors may improve OS rates in patients with ALK+ NSCLC.


Subject(s)
Adult , Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Disease-Free Survival , Female , Humans , Lung Neoplasms/drug therapy , Male , Middle Aged , Mutation , Pemetrexed/therapeutic use , Receptor Protein-Tyrosine Kinases/genetics , Retrospective Studies , Survival Rate , Treatment Outcome
9.
Article in English | WPRIM | ID: wpr-38101

ABSTRACT

Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics. Here, we grouped molecular biomarkers of lung cancers into three categories—mutations, gene rearrangements, and amplifications—and propose expanded guidelines on molecular testing of lung cancers.


Subject(s)
Biomarkers , Gene Rearrangement , Humans , Lung Neoplasms , Lung , Lymphoma , Pathology, Molecular , Phosphotransferases , Precision Medicine , Protein-Tyrosine Kinases , ErbB Receptors
10.
Article in English | WPRIM | ID: wpr-6990

ABSTRACT

PURPOSE: Prognostic factors in patients with pulmonary metastases (PM) from colorectal cancer (CRC) are still controversial. This study assessed oncologic outcomes and prognostic factors in patients with metachronous PM from CRC. MATERIALS AND METHODS: Between June 2003 and December 2011, 122 patients with CRC underwent curative resection of PM detected at least 4 months after CRC resection. Clinico-pathological factors selected from the prospectively maintained database were analyzed retrospectively. RESULTS: The median disease-free interval (DFI) between resection of the primary tumor and detection of PM was 22.0 months (range, 4 to 85 months). Solitary PM were detected in 77 patients (63.1%), with a median maximal tumor diameter of 12.0 mm (range, 2 to 70 mm). Of 52 patients who underwent mediastinal lymph node (LN) dissection, eight patients had LN involvement. Five-year overall survival and disease-free survival (DFS) rates after initial pulmonary metastasectomy were 66.4% and 50.9%, respectively. DFI, mediastinal LN involvement, and the number and distribution of PM were significantly prognostic factors for DFS. In multivariable analysis DFI ≥ 12 months, solitary lesion, and absence of mediastinal LN involvement were independently prognostic for DFS. Of the 122 patients, 48 patients (39.3%) developed recurrent PM a median 13.0 months after initial pulmonary metastasectomy. Recurrent DFI was independently prognostic of DFS in patients who underwent repeated pulmonary metastasectomy. CONCLUSION: There is a potential survival benefit for patients with metachronous PM from CRC who undergo pulmonary metastasectomy, even those with recurrent PM. Pulmonary metastasectomy should be considered in selected patients, particularly those with longer DFI, solitary lesions, and absence of mediastinal LN involvement.


Subject(s)
Colorectal Neoplasms , Disease-Free Survival , Humans , Lymph Nodes , Metastasectomy , Neoplasm Metastasis , Prospective Studies , Retrospective Studies , Survival Rate
11.
Article in English | WPRIM | ID: wpr-32750

ABSTRACT

BACKGROUND: Aquaporin 1 (AQP1) overexpression has been shown to be associated with uncontrolled cell replication, invasion, migration, and tumor metastasis. We aimed to evaluate AQP1 expression in lung adenocarcinomas and to examine its association with clinicopathological features and prognostic significance. We also investigated the association between AQP1 overexpression and epithelial-mesenchymal transition (EMT) markers. METHODS: We examined AQP1 expression in 505 cases of surgically resected lung adenocarcinomas acquired at the Seoul National University Bundang Hospital from 2003 to 2012. Expression of AQP1 and EMT-related markers, including Ecadherin and vimentin, were analyzed by immunohistochemistry and tissue microarray. RESULTS: AQP1 overexpression was associated with several aggressive pathological parameters, including venous invasion, lymphatic invasion, and tumor recurrence. AQP1 overexpression tended to be associated with higher histological grade, advanced pathological stage, and anaplastic lymphoma kinase (ALK) translocation; however, these differences were not statistically significant. In addition, AQP1 overexpression positively correlated with loss of E-cadherin expression and acquired expression of vimentin. Lung adenocarcinoma patients with AQP1 overexpression showed shorter progression-free survival (PFS, 46.1 months vs. 56.2 months) compared to patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter PFS (hazard ratio, 1.429; 95% confidence interval, 1.033 to 1.977; p=.031). CONCLUSIONS: AQP1 overexpression was thereby concluded to be an independent factor of poor prognosis associated with shorter PFS in lung adenocarcinoma. These results suggested that AQP1 overexpression might be considered as a prognostic biomarker of lung adenocarcinoma.


Subject(s)
Adenocarcinoma , Aquaporin 1 , Cadherins , Disease-Free Survival , Epithelial-Mesenchymal Transition , Humans , Immunohistochemistry , Lung , Lymphoma , Multivariate Analysis , Neoplasm Metastasis , Phosphotransferases , Prognosis , Recurrence , Seoul , Tissue Array Analysis , Vimentin
12.
Article in English | WPRIM | ID: wpr-186699

ABSTRACT

Thymic carcinomas are uncommon malignant tumors, and thymic adenocarcinomas are extremely rare. Here, we describe a case of primary thymic adenocarcinoma in a 59-year-old woman. Histological examination of the tumor revealed tubular morphology with expression of cytokeratin 20 and caudal-type homeobox 2 according to immunohistochemistry, suggesting enteric features. Extensive clinical and radiological studies excluded the possibility of an extrathymic primary tumor. A review of the literature revealed only two global cases of primary tubular adenocarcinomas of the thymus with enteric immunophenotype.


Subject(s)
Adenocarcinoma , Female , Genes, Homeobox , Humans , Immunohistochemistry , Keratin-20 , Middle Aged , Thymoma , Thymus Gland
13.
Article in English | WPRIM | ID: wpr-182012

ABSTRACT

BACKGROUND: Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor-type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC. METHODS: IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance. RESULTS: Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p = .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor (EGFR)-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p = .009). CONCLUSIONS: Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in EGFR-mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy.


Subject(s)
Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Cytoplasm , Disease-Free Survival , Epidermal Growth Factor , Humans , Immunohistochemistry , Lung , Membranes , Prognosis , Protein-Tyrosine Kinases , ErbB Receptors
15.
Hanyang Medical Reviews ; : 10-14, 2014.
Article in Korean | WPRIM | ID: wpr-72406

ABSTRACT

Lung cancer is characterized by accumulation of oncogene activation, inactivation of tumor suppressor genes and alteration of epigenetic changes. Fortunately, the past decade has seen remarkable development in molecular pathogenesis and management of lung cancer, especially adenocarcinoma. The discovery of the biologic and therapeutic importance of acquired genetic alterations in 2 genes that encode pharmacologically targetable tyrosine kinases involved in growth factor receptor signaling, epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has raised hope that targeted therapy will improve survival and quality of life of patients with lung cancer. Therefore, molecular testing to detect these 2 mutated genes is more important than ever and has changed the management of the patients with lung cancer and the role of pathologists. Furthermore, as most lung cancer patients present with advanced-stage disease at the time of diagnosis, it is important to detect targetable mutations using small tissue samples or cytology specimens. Here, the author summarizes the practical impact of the molecular testing of lung cancer and introduces the current knowledge of lung cancer pathology.


Subject(s)
Adenocarcinoma , Diagnosis , Epigenomics , Genes, Tumor Suppressor , Hope , Humans , Lung Neoplasms , Lung , Lymphoma , Molecular Diagnostic Techniques , Oncogenes , Pathology , Phosphotransferases , Quality of Life , ErbB Receptors , Tyrosine
17.
Article in English | WPRIM | ID: wpr-128038

ABSTRACT

Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor. However, the prevalence of the ALK fusion is low, so accurate patient identification is crucial for successful treatment using ALK inhibitors. Furthermore, most patients with lung cancer present with advanced-stage disease at the time of diagnosis, so it is important for pathologists to detect ALK-rearranged patients while effectively maximizing small biopsy or cytology specimens. In this review, we propose a guideline recommendation for ALK testing approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.


Subject(s)
Biopsy , Diagnosis , Gene Rearrangement , Humans , Lung Neoplasms , Lung , Lymphoma , Pathology , Phosphotransferases , Prevalence , Protein-Tyrosine Kinases
18.
Article in English | WPRIM | ID: wpr-74265

ABSTRACT

BACKGROUND: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. METHODS: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. RESULTS: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. CONCLUSION: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.


Subject(s)
1-Methyl-3-isobutylxanthine , Adenocarcinoma , Blotting, Western , Cell Line , Cell Transformation, Neoplastic , Chromogranin A , Cisplatin , Drug Resistance, Neoplasm , Epidermal Growth Factor , Etoposide , Humans , Lung , Lung Neoplasms , Parents , Piperidines , Poly(ADP-ribose) Polymerases , Protein-Tyrosine Kinases , Quinazolines , ErbB Receptors , Small Cell Lung Carcinoma , Synaptophysin , Erlotinib Hydrochloride
19.
Article in English | WPRIM | ID: wpr-65410

ABSTRACT

BACKGROUND: Epithelial-mesenchymal transition (EMT) is an important step in the invasion and progression of cancer and in the development of chemoresistance by cancer cells. METHODS: To address the clinical significance of the EMT pathway in lung adenocarcinoma and the association of the pathway with histological subtype, we examined 193 surgically resected lung adenocarcinoma samples for the expression of representative EMT-related proteins (E-cadherin, beta-catenin, and vimentin) by immunohistochemistry. Histological subtypes were classified according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The results for EMT-related protein expression were analyzed for correlation with clinicopathological features and with survival. RESULTS: The loss of E-cadherin expression and aberrant beta-catenin expression were significantly associated with larger tumor size, pleural invasion, lymphatic/vascular invasion, and advanced pathological stage (p<0.05). The alteration of the E-cadherin/beta-catenin complex was least frequently observed in the lepidic-predominant group, but these associations were not statistically significant. In the multivariate analysis, altered E-cadherin/beta-catenin complex expression was found to be an independent poor prognostic factor (p=0.017; hazard ratio, 1.926; 95% confidence interval, 1.119 to 3.314). CONCLUSIONS: The alteration of the expression of the E-cadherin/beta-catenin complex was associated with aggressive tumor behavior in lung adenocarcinoma.


Subject(s)
Adenocarcinoma , beta Catenin , Cadherins , Epithelial-Mesenchymal Transition , Immunohistochemistry , Lung , Lung Neoplasms , Multivariate Analysis , Proteins
20.
Article in English | WPRIM | ID: wpr-65409

ABSTRACT

BACKGROUND: The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (EGFR) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate EGFR mutational status as determined by each method with the clinical response to EGFR tyrosine kinase inhibitors (TKIs). METHODS: Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the EGFR gene (exons 18-21). RESULTS: Mutations in the EGFR gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing. A total of 44 mutations (72%) were found by at least one of the three methods, and the concordances among the results were relatively high (82-85%; kappa coefficient, 0.713 to 0.736). There were 15 discordant cases (25%) among the three different methods. CONCLUSIONS: All three EGFR mutation tests had good concordance rates (over 82%) for FFPE samples. These results suggest that if the DNA quality and enrichment of tumor cells are assured, then DS, PNA clamping, and pyrosequencing are appropriate methods for the detection of EGFR mutations.


Subject(s)
Constriction , DNA , Genes, erbB-1 , Humans , Lung , Lung Neoplasms , Peptide Nucleic Acids , Polymerase Chain Reaction , Protein-Tyrosine Kinases , ErbB Receptors , Tyrosine
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