p40 Immunohistochemistry Is an Excellent Marker in Primary Lung Squamous Cell Carcinoma

Khairunisa Ahmad Affandi,Nur Maya Sabrina Tizen,Muaatamarulain Mustangin,Reena Rahayu Md Zin 대한병리학회 2018 Journal of Pathology and Translational Medicine Vol.52 No.5

Background: Lung cancer is the third most common cancer worldwide. With major advances in the molecular testing of lung cancers and the introduction of targeted therapies, the distinction between adenocarcinoma and squamous cell carcinoma as well as pathologic subtyping has become important. Recent studies showed that p40 is highly specific for squamous and basal cells and is superior to p63 for diagnosing lung squamous cell carcinoma. The aim of this study was to evaluate the use of p40 immunohistochemical stain in the diagnosis of non-small cell lung carcinoma and its potential to replace current p63 antibody as the best immunohistochemical squamous marker. Methods: Seventy formalin-fixed paraffin-embedded cases previously diagnosed as primary lung squamous cell carcinoma (n = 35) and lung adenocarcinoma (n = 35) from January 2008 to December 2016 were retrieved. The results of tumour cell immunoreactivity for p40 and p63 antibodies in lung squamous cell carcinoma and lung adenocarcinoma were compared. Results: p40 was expressed in 27 cases of lung squamous cell carcinoma (77.1%). All cases of lung adenocarcinoma (35/35, 100%) were negative for p40. p63 expression was positive in 30 cases of lung squamous cell carcinoma (85.7%) and 13 cases of lung adenocarcinoma (37.1%). Reactivity for both p40 and p63 in lung squamous cell carcinoma was strong and diffuse, whereas variable reactivity was observed in lung adenocarcinoma. Conclusions: p40 is an excellent marker for distinguishing lung squamous cell carcinoma from adenocarcinoma, and p40 expression is equivalent to p63 expression in lung squamous cell carcinoma.

Comprehensive Cytomorphologic Analysis of Pulmonary Adenoid Cystic Carcinoma: Comparison to Small Cell Carcinoma and Non-pulmonary Adenoid Cystic Carcinoma

김석휘,한정호,주진아,김호중 대한병리학회 2015 Journal of Pathology and Translational Medicine Vol.49 No.6

Background: Cytologic diagnosis of pulmonary adenoid cystic carcinoma (AdCC) is frequently challenging and differential diagnosis with small cell carcinoma is often difficult. Methods: Eleven cytologically diagnosed cases of pulmonary AdCC were collected and reviewed according to fifteen cytomorphologic characteristics: small cell size, cellular uniformity, coarse chromatin, hyperchromasia, distinct nucleolus, frequent nuclear molding, granular cytoplasm, organoid cluster, sheet formation, irregular border of cluster, hyaline globule, hyaline basement membrane material, individual cell necrosis or apoptotic body, and necrotic background. Twenty cases of small cell carcinoma and fifteen cases of non-pulmonary AdCC were also reviewed for the comparison. Results: Statistically significant differences were identified between pulmonary AdCC and small cell carcinoma in fourteen of the fifteen cytomorphologic criteria (differences in sheet formation were not statistically significant). Cellular uniformity, distinct nucleolus, granular cytoplasm, distinct cell border, organoid cluster, hyaline globule, and hyaline basement membrane material were characteristic features of AdCC. Frequent nuclear molding, individual cell necrosis, and necrotic background were almost exclusively identified in small cell carcinoma. Although coarse chromatin and irregular cluster border were observed in both, they favored the diagnosis of small cell carcinoma. Hyaline globules were more frequently seen in non-pulmonary AdCC cases. Conclusions: Using the fifteen cytomorphologic criteria described by this study, pulmonary AdCC could be successfully distinguished from small cell carcinoma. Such a comprehensive approach to an individual case is recommended for the cytologic diagnosis of pulmonary AdCC.

췌장에 전이된 폐 소세포암

이태훈 ( Tae Hun Lee ),정일권 ( Il Kwun Chung ),길효욱 ( Hyo Wook Gil ),박현준 ( Hyun Jun Park ),김영훈 ( Young Hoon Kim ),박상흠 ( Sang Heum Park ),김홍수 ( Hong Soo Kim ),이문호 ( Moon Ho Lee ),김선주 ( Sun Joo Kim ),조현득 ( Hy 대한소화기학회 2003 대한소화기학회지 Vol.41 No.5

The incidence of small cell carcinomas of the pancreas is approximately 1% of malignant pancreatic diseases. About 10% of metastatic small cell carcinomas of the pancreas are originated from the lung. Diagnosis of primary small cell carcinomas of the pancreas should be done after exclusion of any extraabdominal presence of small cell carcinomas. Metastasis-induced acute pancreatitis is unusual and the case manifested by primary pancreatic cancer is also unusual. We experienced a rare case of metastatic small cell carcinoma of the pancreas, which was suspected to be originated from the lung. He presented with clinical features of acute pancreatitis and was diagonsed having small cell carcinoma of the pancreas by histologic examination. The radiographic finding on his chest was normal, but small cell lung cancer was detected by more active evaluation of the lung. (Korean J Gastroenterol 2003;41:417-420)

Enhanced Sensitivity to Gefitinib after Radiation in Non-Small Cell Lung Cancer Cells

( Yun Jung Choi ),( Jin Kyung Rho ),( Dae Hyun Back ),( Hye Ryoun Kim ),( Jae Cheol Lee ),( Cheol Hyeon Kim ) 대한결핵 및 호흡기학회 2011 Tuberculosis and Respiratory Diseases Vol.71 No.4

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. Methods: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. Results: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. Conclusion: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.

소세포폐암에 병발한 혈청 Anti - Hu Antibody 양성인 가성 장폐쇄 1 예

예병덕(Byong Duk Ye),박완범(Wan Bum Park),이종열(Jong Yeul Lee),김지원(Ji Won Kim),김병관(Byeong Gwan Kim),김주성(Joo Sung Kim),정현채(Hyun Chae Jung),송인성(In Sung Song) 대한소화기학회 2001 대한소화기학회지 Vol.38 No.5

Intestinal pseudoobstruction is a clinical syndrome presenting with symptoms and signs of intestinal obstruction without the evidence of a structural obstructing lesion. Recently, case reports have revealed an association between intestinal pseudoobstruction and various malignancies, especially small cell lung carcinoma. In the paraneoplastic intestinal pseudoobstruction associated with small cell lung carcinoma, anti-neuronal nuclear antibody called anti-Hu antibody was positive in most patients. This report describes a case of 53-year-old man who complained of diffuse, intermittent colicky abdominal pain, nausea, and vomiting. He was diagnosed as having syndrome of inappropriate ADH, intestinal pseudoobstruction, and small cell lung carcinoma. The presence of anti-Hu antibody in patient's serum supports the diagnosis of paraneoplastic intestinal pseudoobstruction associated with small cell lung carcinoma. (Korean J Gastroenterol 2001;38:376-380)

P183 : MicroRNA-1290 mediated cellular mechanism promotes asiatic acid induced apoptosis is in a549 non small cell lung carcinoma cells

( Ho Jung Jung ),( Min Jung Kim ),( Hae Jeong Youn ),( Nam Kyung Roh ),( Soo Young Kim ),( Yu Ri Kim ),( Yu Na Lee ),( Jae Wook Jung ),( Yang Won Lee ),( Yong Beom Choe ),( Kyu Joong Ahn ),( In Sook A 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Asiatic acid is a putative anticancer agent in several types of cancer cells. Researches of its biological role in negative regulation of cell growth have focused on the extent of induction of apoptosis in a cell-type-specific manner. Objectives: To identify the mechanisms underlying asiatic acid-induced downregulation of BCL2. Methods: MicroRNA microarray analysis was used to investigate the effect of asiatic acid treatment of A549 cells on miRNA expression profiles. We used quantitative RT-PCR to confirm the asiatic acid-induced increase in miR-1290 level with primers specific for the mature miR-1290 sequence. We also assessed the effect of asiatic acid on the levels of BCL2 in A549 cells using western blot analysis. Results: We identified an important regulator of asiatic acid-induced cell death, microRNA (miR)-1290, which sensitizes cells to Asiatic acid-induced cytotoxicity and negatively regulates BCL2 expression. Asiatic acid significantly upregulated miR-1290, and asiatic acid-induced cell death was shown to be dependent on miR-1290 activity. Molecular assays demonstrated that BCL2 mRNA is a direct target of miR-1290-mediated RNA interference. Conclusion: The findings of the present study suggest that miR-1290 suppresses cell viability and cell cycle progression. Our results provide insight into miR-1290-mediated cellular mechanisms in asiatic acid-treated A549 non-small cell lung carcinoma cells.

miR-4487 Enhances Gefitinib-Mediated Ubiquitination and Autophagic Degradation of EGFR in Non-Small Cell Lung Cancer Cells by Targeting USP37

김미성,김소희,양세훈,김민석 대한암학회 2022 Cancer Research and Treatment Vol.54 No.2

Purpose With the identification of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) cells, EGFR–tyrosine kinase inhibitors (TKIs) are being used widely as the first-line of treatment in NSCLC. These inhibitors block auto-phosphorylation of activated EGFR by competing with ATP binding and mediate EGFR degradation independent of exogenous epidermal growth factor, which is associated with the mutation variants of EGFR. However, the precise mechanisms underlying the TKI-mediated EGFR degradation are still unclear. Materials and Methods To examine the physiological roles of miR-4487 and ubiquitin-specific peptidase 37 (USP37) in gefitinib-mediated EGFR degradation in NSCLC cells, multiple NSCLC cell lines were applied. The level of EGFR expression, apoptosis marker, and autophagic flux were determined by western blot. Expression level of miR-4487 and cell-cycle arrest was analyzed by TaqMan assay and flow cytometry respectively. Results We found that gefitinib mediates EGFR degradation under normal culture conditions, and is dependent on autophagic flux and the mutation variants of EGFR. Gefitinib reduced expression levels of USP37, which mediated EGFR degradation similar to gefitinib. Our results also showed a gefitinib-mediated increase in endogenous miR-4487 level and presented evidence for the direct targeting of USP37 by miR-4487, resulting in the sequential enhancement of ubiquitination, autophagy, and EGFR degradation. Thus, the depletion of USP37 and overexpression of miR-4487 led to an increase in gefitinib-mediated apoptotic cell death. Conclusion These data suggest that miR-4487 is a potential target for treating NSCLC, and miR-4487/USP37-regulated EGFR degradation is a determinant for developing gefitinib resistance. PurposeWith the identification of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) cells, EGFR–tyrosine kinase inhibitors (TKIs) are being used widely as the first-line of treatment in NSCLC. These inhibitors block auto-phosphorylation of activated EGFR by competing with ATP binding and mediate EGFR degradation independent of exogenous epidermal growth factor, which is associated with the mutation variants of EGFR. However, the precise mechanisms underlying the TKI-mediated EGFR degradation are still unclear.Materials and MethodsTo examine the physiological roles of miR-4487 and ubiquitin-specific peptidase 37 (USP37) in gefitinib-mediated EGFR degradation in NSCLC cells, multiple NSCLC cell lines were applied. The level of EGFR expression, apoptosis marker and autophagic flux were determined by western blot. Expression level of miR-4487 and cell cycle arrest was analyzed by TaqMan assay and flow cytometry respectively.ResultsWe found that gefitinib mediates EGFR degradation under normal culture conditions, and is dependent on autophagic flux and the mutation variants of EGFR. Gefitinib reduced expression levels of USP37, which mediated EGFR degradation similar to gefitinib. Our results also showed a gefitinib-mediated increase in endogenous miR-4487 level and presented evidence for the direct targeting of USP37 by miR-4487, resulting in the sequential enhancement of ubiquitination, autophagy, and EGFR degradation. Thus, the depletion of USP37 and overexpression of miR-4487 led to an increase in gefitinib-mediated apoptotic cell death. ConclusionThese data suggest that miR-4487 is a potential target for treating NSCLC, and miR-4487/USP37-regulated EGFR degradation is a determinant for developing gefitinib resistance.

Identification of Differentially Expressed Genes in Human Small Cell Lung Carcinoma Using Subtractive Hybridization

Ahn, Seung-Ju,Choi, Jae-Kyoung,Joo, Young Mi,Lee, Min-A,Choi, Pyung-Rak,Lee, Yeong-Mi,Kim, Myong-Shin,KIm, So-Young,Jeon, Eun-Hee,Min, Byung-In,Kim, Chong-Rak THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCIEN 2004 Journal of biomedical laboratory sciences Vol.10 No.3

Lung cancer is a leading cause of cancer death worldwide; however, despite major advances in cancer treatment during the past two decades, the prognostic outcome of lung cancer patients has improved only minimally. This is largely due to the inadequacy of the traditional screening approach of diagnosis in lung cancer, which detects only well-established overt cancers and fails to identify precursor lesions in premalignant conditions of the bronchal tree. In recent years this situation has fundamentally changed with the identification of molecular abnormalities characteristic of premalignant changes; these concern tumour suppressor genes, loss of heterozygosity at crucial sites and activation of oncogenes. Basic knowledge at the molecular level has extremely important chical implications with regard to early diagnosis, risk assessment and prevention, and therapeutic targets. In this study we used a "cap-finder" subtractive hybndization method, "long distance" polymerase chain reaction (PCR), streptavidin magnetic beads mediated subtraction, and spin column chromatography to detect differential expression genes of human small cell lung carcinoma. We have now isolated ninety two genes that expressed differentially in the human small cell lung carcinoma cells and analyzed of 12 clones with sequencing, nine cDNAs include tapasin (NGS-17) mRNA, BC200 alpha scRNA, chromosome 12q24 PAC RPC13-462E2, protein phosphatase 1 (PPPICA), translocation protein 1 (TLOCl), ribosomal protein S24 (WS24) mRNA, protein phosphatase (PPEF2), cathepsin Z, MDM2 gene and three novel genes. They may be oncogenesis-related proteins.

소세포 폐암의 갑상선전이 1예

장리라,최영식,박요한,문대성,김자경,김성은,최인수,유찬희,남성진 고신대학교 의과대학 2008 고신대학교 의과대학 학술지 Vol.23 No.3

Metastasis to the thyroid gland is usually considered uncommon. The most frequent sites of the primary tumor include the kidney, breast and lung. Its presence often indicates poor prognosis. Metastases represent the advanced stage of the tumors and fine needle aspiration cytology is and important way of diagnosis in thyroid metastasis. we experienced a case of Metastatic Small cell Lung Carcinoma to the Thyroid Gland. A 58-year-old man with Graves' disease diagnosed pulmonary nodule in the left upper lung field on his chest X-ray film. The patient's thyroid gland was diffusely swollen, and elastic to hard. A thyroid ultrasonography showed 1cm sized hypodense nodule on the left thyroid gland. The patient underwent a ultrasonography guided fine needle aspiration cytology of the mass. Cytological diagnosis was a metastatic small cell carcinoma. Then Chemotherapy was administered to the patient. The authors report this rare case of metastatic small cell lung carcinoma to the thyroid with literature review.

Identification of Differentially Expressed Genes in Human Small Cell Lung Carcinoma Using Subtractive Hybridization

Ahn Seung-Ju,Choi Jae-Kyoung,Joo Young Mi,Lee Min-A,Choi Pyung-Rak,Lee Yeong-Mi,Kim Myong-Shin,Kim So-Young,Jeon Eun-Hee,Min Byung-In,Kim Chong-Rak 대한의생명과학회 2004 Biomedical Science Letters Vol.10 No.3

Lung cancer is a leading cause of cancer death worldwide; however, despite major advances in cancer treatment during the past two decades, the prognostic outcome of lung cancer patients has improved only minimally. This is largely due to the inadequacy of the traditional screening approach of diagnosis in lung cancer, which detects only well­established overt cancers and fails to identify precursor lesions in premalignant conditions of the bronchial tree. In recent years this situation has fundamentally changed with the identification of molecular abnormalities characteristic of premalignant changes; these concern tumour suppressor genes, loss of heterozygosity at crucial sites and activation of oncogenes. Basic knowledge at the molecular level has extremely important clinical implications with regard to early diagnosis, risk assessment and prevention, and therapeutic targets. In this study we used a 'cap-finder' subtractive hybridization method, 'long distance' polymerase chain reaction (PCR), streptavidin magnetic beads mediated subtraction, and spin column chromatography to detect differential expression genes of human small cell lung carcinoma. We have now isolated ninety two genes that expressed differentially in the human small cell lung carcinoma cells and analyzed of 12 clones with sequencing, nine cDNAs include tapasin (NGS-17) mRNA, BC200 alpha scRNA, chromosome 12q24 PAC RPCI3-462E2, protein phosphatase 1 (PPPICA), translocation protein 1 (TLOC1), ribosomal protein S24 (RPS24) mRNA, protein phosphatase (PPEF2), cathepsin Z, MDM2 gene and three novel genes. They may be oncogenesis­related proteins.