• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3927-3932
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• 2014

Background: Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. Patients and Methods: EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. Results: EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5ng/ml seemed to be higher than patients with a concentration over 5ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. Conclusions: The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

• 한국동물위생학회지
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• 제41권1호
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• pp.57-61
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• 2018

Canine peripheral nerve sheath tumors (PNSTs) are spindle cell tumors that arise from Schwann cells, perineural cells, fibroblasts or all of them. Based on the morphology and biologic behavior, PNSTs are divided into benign PNST (BPNST) and malignant PNST (MPNST) forms. The aim of this study is to diagnose the two cases of neoplastic tissue samples with features of PNSTs by the histopathology and immunohistochemistry. The study was performed using two specimens from small animal clinic. The first case, A was a mass, 3~4 cm in diameter, extruded from vaginal mucosa of 10-year-old spayed female mixed-breed dog. And the second case, B was a subcutaneous mass, 1.5 cm in diameter, which is originated from right hind leg of 9-year-old castrated male mixed-breed dog. Two cases were stained with hematoxylin and eosin (H&E) for histopathological examination. And also immunohistochemistry (IHC) was performed by the avidin-biotin peroxidase complex (ABC) method with antibodies specific for the following proteins: S-100 protein, smooth muscle actin (SMA) and epidermal growth factor receptor (EGFR). In results, Antoni B schwannoma pattern characterized by pleomorphic, round and fusiform polygonal cells was seen in A. In B, Antoni A pattern, densely packed spindle cells arranged in interlacing bundles was seen in addition to Antoni B pattern. In IHC, cytoplasms of neoplastic cells were diffusely labeled for S-100 expression in A and B. For SMA, both A and B show negative expression. And for EGFR, A shows negative expression but B shows partially positive expression in areas of Antoni B schwannoma pattern. The histopathologic features of two cases coupled with the S-100 immunoreactivity led to a diagnosis of PNST. For SMA, both A and B show negative expression. The diagnosis of A will be a BPNST with the negative result and B will be a MPNST with the positive result for EGFR.

• Radiation Oncology Journal
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• 제28권2호
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• pp.57-63
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• 2010

목 적: 방사선 치료를 받은 코인두암 환자의 치료 전 조직을 면역조직화학염색하여 생체분자적 예후인자를 찾고자 하였다. 대상 및 방법: 1998년부터 2006년까지 방사선 치료를 받은 코인두암환자는 68명이었다. 이중 38명의 환자에서 면역조직화학염색을 위한 파라핀 블록을 찾을 수 있었다. 전체 환자 중 31명은 미분화암종이었고, 7명은 편평세포암종이었다. 전체 환자의 84%가 2002 American Joint Committee on Cancer Stage III or IV 환자였다. 전체 환자의 파라핀 블록을 이용하여 Met, COX-2, epidermal growth factor receptor (EGFR), nm23-H1에 대해 면역조직화학염색을 시행하였다. 결 과: 전체 환자의 중앙 추적 기간은 30개월이었고 생존 환자의 중앙 추적 기간은 39개월이었다. 높은(${\geq}50%$) Met 발현을 보인 환자들의 5년 생존율은 48%, 낮은 Met 발현을 보인 환자들의 5년 생존율은 84%로 이는 통계적으로 유의한 차이를 보였다(p=0.02). Met 발현 정도는 다변량 분석에서도 유의한 인자로 분석되었다(p=0.01). Met 발현은 종양의 병기, 성별, 나이, 항암제나 방사선 치료에 대한 반응 정도와 상관관계를 보이지 않았다. Met 발현 정도는 COX-2 발현과 중등도의 상관관계를 보였으나(Pearson coefficient 0.496, p<0.01), COX-2 발현은 전체생존율에 영향을 미치지 않았다. 본 연구에서는 nm23-H1이나 EGFR의 발현은 예후인자가 아닌 것으로 분석되었다. 결 론: 방사선치료를 받은 코인두암에서, 높은(${\geq}\;50%$) Met 발현은 전체생존율에 영향을 미치는 독립적인 예후인자일 가능성이 있다.

• 대한치과교정학회지
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• 제28권5호
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• pp.775-782
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• 1998

동소 mRNA 보합결합법을 이용하여 백서의 실험적 치아 이동시 치은 상피에 있어서 견인측과 압박측의 표피성장인자 수용체의 발현을 관찰하여 다음과 같은 결과를 얻었다. 1. 대조군은 구강 상피의 기저세포층, 극세포층, 과립세포층, 각화층의 전층에 걸쳐 미약한 염색상을 보였으며 압박측, 견인측의 차이는 없었다. 2. 장치의 장착 시간 경과에 따라 반응의 정도가 증가하는 양상으로 나타났으며, 그 분포도 하부의 기저세포층에서 상부의 각화층으로 확산되었다. 전반적으로 반응정도에 있어 압박측과 견인측의 차이는 없었으나, 단지 장치 장착후 7일의 견인측 각화층에서만 압박측보다 반응의 정도가 약하게 나타났다. 3. 장치를 제거하면 시간이 경과함에 따라 표피성장인자의 발현 정도가 감소하여 제거후 7일에는 전층에 걸펴 경미한 양성반응을 보였으며 압박측과 견인측간의 차이는 없었다. 이상의 결과에서 미루어 볼 때 치아의 이동시에 EGFR의 증가는 치아 이동시에 가해지는 물리적 stress를 포함한 외부 환경의 변화로부터 치은 상피를 포함한 치주조직의 항상성을 유지하기 위한 반응으로 여겨진다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8069-8073
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• 2014

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC, and to determine whether these two markers correlate with conventional parameters of prognosis. Materials and Methods: Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal. The intensity of EGFR staining was scored on a scale of 0-3+: 0 no staining; 1+ when a weak membrane staining was observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense dark brown staining delineated the membrane. To determine the relationship between EGFR expression and p53, we performed double staining in the same HCC specimens. Results: By immunohistochemical staining, p53 protein was detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity of p53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked to histological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFR intensity (p=0.014). Conclusions: Our results suggest that overexpression of p53 and EGFR plays an important role in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuable predictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5177-5182
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• 2012

Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Conclusion: Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR-TKImonotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.

• 대한임상검사과학회지
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• 제55권1호
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• pp.16-28
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• 2023

폐암은 크게 소세포성 폐암과 비소세포성 폐암으로 구분되며 비소세포성폐암이 차지하는 비율은 약 70%~80%이다. 비소세포성폐암 중 폐선암은 전체 폐암의 약 40%를 차지한다. 최근 유전자 프로파일링 기술이 발전하면서 종양의 발생 및 성장에 중요한 종양 유전자와 종양 억제 유전자의 변이에 대한 연구가 활발히 진행되어 폐암을 유발하는 특정 유전자들이 발견되면서 생존율에 큰 영향을 미치게 되었으며 특히 폐선암은 차세대 염기서열 분석법(next generation sequencing, NGS)을 이용한 동반진단을 통해 표적 치료로 생존을 높이는 데 도움을 얻을 수 있다. 본 연구는 한국인에서 폐선암을 유발하는 유전자 변이 검출을 위해 비소세포성폐암 환자의 파라핀 포매조직(formalin-fixed paraffin-embedded)으로 hematoxylin and eosin 염색을 시행하여 폐선암을 구분하였으며 정확한 폐선암 조직을 분류하기 위해 면역조직화학(immunohistochemistry, IHC)염색을 시행하였다. 그 결과를 바탕으로 NGS를 이용하여 유전자 변이의 종류와 패턴을 분석하였고 폐암을 유발하는 가장 대표적인 원인인 흡연과의 관계를 확인하였다. NGS 결과 단일염기서열변이(single nucleotide variation, SNV), 복제수변이 (copy number variation, CNV), 유전자 재배열을 확인하였으며 폐선암에서 SNV는 TP53 (44.6%), EGFR (35.7%), KRAS (10.7%), PIK3CA (6.2%), CDKN2A (4.4%) 순으로 발생하였고 CNV의 경우 EGFR (14%)이 가장 빈번하게 발생하였다. 또한 ALK, ROS1, RET 과 같은 유전자 재배열을 확인하였다. NGS의 신뢰도를 확인을 위하여 기존에 사용되고 있는 유전자 검사방법인 PCR-EGFR, IHC-ALK (D5F3), FISH-ROS1 검사를 추가적으로 시행하여 NGS 결과와 일치도를 확인하였다. 이 연구는 폐선암 환자에 대한 NGS가 여러 유전자의 돌연변이를 동시에 확인하여 치료 전략에 더욱 긍정적인 이익을 줄 수 있음을 보여준다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.3023-3027
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• 2015

Purpose: To investigate the effects of epidermal growth factor receptor (EGFR), cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on local control (LC) and overall survival (OS) in patients with locally advanced head and neck cancer (LAHNC) who were administered radiotherapy (RT). Materials and Methods: Twenty-six patients who were admitted to Uludag University Medical Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV) were included in this study. Gene expression was evaluated in tumor tissues and peripheral blood. RNA isolation was performed on paraffinized tumor tissues and peripheral blood samples obtained before RT (BR). The densities of the obtained RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR, CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green method and data were analyzed with the ${\Delta}{\Delta}Ct$ method. The same process was repeated for peripheral blood samples taken after RT (AR). Results: The female/male ratio was 3:23 and the mean age was 56.5 years (38-75years). After radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be correlated according to Pearson correlation analysis(p=0.049). This result indicates a possibility of remaining positive for CK19 and CK20 in the peripheral blood even after RT in patients with CK19, CK20, and EGFR positive tumors before RT. There was a statistically significant correlation between survinin levels measured BR and AR (p=0.028). Conclusions: In this study, we found that patients with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain less benefit from radiotherapy. A wider patient population and advanced protein analyses are necessary in order to increase the reliability of our findings.

• BMB Reports
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• 제40권4호
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• pp.467-474
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• 2007

Autosomal recessive polycystic kidney disease (ARPKD) is one of the important genetic disorders in pediatric practice. Mutation of the polycystic kidney and hepatic disease gene 1 (PKHD1) was identified as the cause of ARPKD. The gene encodes a 67-exon transcript for a large protein of 4074 amino acids termed fibrocystin, but its function remains unknown. The neoplastic-like in cystic epithelial proliferation and the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) axis overactivity are known as the most important characteristics of ARPKD. Since the misregulation of $Ca^{2+}$ signaling may lead to aberrant structure and function of the collecting ducts in kidney of rat with ARPKD, present study aimed to investigate the further mechanisms of abnormal proliferation of cystic cells by inhibition of PKHD1 expression. For this, a stable PKHD1-silenced HEK-293T cell line was established. Then cell proliferation rates, intracellular $Ca^{2+}$ concentration and extracellular signal-regulated kinase 1/2 (ERK1/2) activity were assessed after treatment with EGF, a calcium channel blocker and agonist, verapamil and Bay K8644. It was found that PKHD1-silenced HEK-293T cell lines were hyperproliferative to EGF stimulation. Also PKHD1-silencing lowered the intracellular $Ca^{2+}$ and caused EGF-induced ERK1/2 overactivation in the cells. An increase of intracellular $Ca^{2+}$ in PKHD1-silenced cells repressed the EGF-dependent ERK1/2 activation and the hyperproliferative response to EGF stimulation. Thus, inhibition of PKHD1 can cause EGF-induced excessive proliferation through decreasing intracellular $Ca^{2+}$ resulting in EGF-induced ERK1/2 activation. Our results suggest that the loss of fibrocystin may lead to abnormal proliferation in kidney epithelial cells and cyst formation in ARPKD by modulation of intracellular $Ca^{2+}$.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2735-2738
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• 2012

Background: Our objective was to clarify the clinical and biological characteristics of basal-like breast cancer (BLBC) and non-basal-like breast cancer (TN3BKE) in Heilongjiang. Methods: We examined, by immunohistochemistry, expression of biological markers cytokeratin (CK) 5/6 and epidermal growth factor receptor (EGFR) and B cell specific moloney murine leukemia virus integration site 1( Bmi-1) in triple-negative breast cancer (TNBC). We studied the correlation between BLBC and several factors related to tumor progression, along with its prognostic value. Results: In the 229 cases of operable TNBC, BLBC was detected in 178 (77.7%) and TN3BKE- in 51 (22.2%). There was no significant difference in clinicopathological factors between them, However, BLBC was significantly associated with Bmi-1 expression (P=0.000) and shorter disease-free survival (DFS) (P = 0.045) and overall survival (OS) (P = 0.041). Conclusions: Compared with the non-basal group, patients with BLBC have a high expression of Bmi-1 and a poor prognosis.