Journal of Pathology and Translational Medicine

Reviews

Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group: Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee; J Pathol Transl Med. 2021;55(3):181-191. Published online May 11, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.23

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Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

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Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing
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Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
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Lung Cancer in Korea
Sehhoon Park, Chang-Min Choi, Seung-Sik Hwang, Yoon-La Choi, Hyae Young Kim, Young-Chul Kim, Young Tae Kim, Ho Yun Lee, Si Yeol Song, Myung-Ju Ahn
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Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group: Dong Hoon Shin, Hyo Sup Shim, Tae Jung Kim, Heae Surng Park, Yun La Choi, Wan Seop Kim, Lucia Kim, Sun Hee Chang, Joon Seon Song, Hyo jin Kim, Jung Ho Han, Chang Hun Lee, Geon Kook Lee, Se Jin Jang; J Pathol Transl Med. 2019;53(3):153-158. Published online February 28, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.22

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Abstract PDF

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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Improving non-small-cell lung cancer survival through molecular characterization: Perspective of a multidisciplinary expert panel
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Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
Journal of Pathology and Translational Medicine.2021; 55(3): 181. CrossRef
Current status and future perspectives of liquid biopsy in non-small cell lung cancer
Sunhee Chang, Jae Young Hur, Yoon-La Choi, Chang Hun Lee, Wan Seop Kim
Journal of Pathology and Translational Medicine.2020; 54(3): 204. CrossRef
Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center
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Original Articles

Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases: Taebum Lee, Boram Lee, Yoon-La Choi, Joungho Han, Myung-Ju Ahn, Sang-Won Um; J Pathol Transl Med. 2016;50(3):197-203. Published online April 18, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.09

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Abstract PDF

Background
Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy.
Methods
In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features.
Results
All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had ALK mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation.
Conclusions
EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

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Giuseppe Lo Russo, Martina Imbimbo, Giulia Corrao, Claudia Proto, Diego Signorelli, Milena Vitali, Monica Ganzinelli, Laura Botta, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino
Oncotarget.2017; 8(35): 59889. CrossRef
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Gaetano Rocco, Alessandro Morabito, Alessandra Leone, Paolo Muto, Francesco Fiore, Alfredo Budillon
The International Journal of Biochemistry & Cell Biology.2016; 78: 173. CrossRef
A long-term survivor of non-small-cell lung cancer harboring concomitant EGFR mutation and ALK translocation
Fumio Imamura, Takako Inoue, Madoka Kimura, Kazumi Nishino, Toru Kumagai
Respiratory Medicine Case Reports.2016; 19: 137. CrossRef

Membranous Insulin-like Growth Factor-1 Receptor (IGF1R) Expression Is Predictive of Poor Prognosis in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma: Eunhyang Park, Soo Young Park, Hyojin Kim, Ping-Li Sun, Yan Jin, Suk Ki Cho, Kwhanmien Kim, Choon-Taek Lee, Jin-Haeng Chung; J Pathol Transl Med. 2015;49(5):382-388. Published online August 4, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.10

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Abstract PDF

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.

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Tatiana Shaurova, Letian Zhang, David W. Goodrich, Pamela A. Hershberger
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Head & Neck.2019; 41(1): 198. CrossRef
Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection
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Overexpression of lncRNA EGFR‑AS1 is associated with a poor prognosis and promotes chemotherapy resistance in non‑small cell lung cancer
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Mojca Humar, Izidor Kern, Gregor Vlacic, Vedran Hadzic, Tanja Cufer
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IGF1R depletion facilitates MET-amplification as mechanism of acquired resistance to erlotinib in HCC827 NSCLC cells
Dianna Hussmann, Anne Tranberg Madsen, Kristine Raaby Jakobsen, Yonglun Luo, Boe Sandahl Sorensen, Anders Lade Nielsen
Oncotarget.2017; 8(20): 33300. CrossRef
Upregulated Neuro-oncological Ventral Antigen 1 (NOVA1) Expression Is Specific to Mature and Immature T- and NK-Cell Lymphomas
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International Journal of Molecular Sciences.2016; 17(5): 763. CrossRef

Cytologic Features of ALK-Positive Pulmonary Adenocarcinoma: Seung Yeon Ha, Jungsuk Ahn, Mee Sook Roh, Joungho Han, Jae Jun Lee, Boin Lee, Jun Yim; Korean J Pathol. 2013;47(3):252-257. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.252

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Abstract PDF

Background

The aim of this study was to determine the cytologic features of anaplastic lymphoma kinase (ALK) expressing pulmonary adenocarcinoma.

Methods

We analyzed the cytopathological findings of 15 cases of endobronchial ultrasound guided aspiration and a case of bronchial washing. These cases were selected based on the histomorphology of ALK-rearranged lung adenocarcinoma.

Results

Cytology showed mucinous (81.3%) and hemorrhagic (50%) backgrounds. The cells were arranged in tubulopapillary or tubulocribriform patterns (93.8%), and clusters (56.3%) admixed with signet ring cell features (87.5%). The tumor cells were monotonous and uniform with vesicular nuclei and a small nucleolus.

Conclusions

The characteristic findings were sheets showing a tubulopapillary or tubulocribriform appearance, with vesicular nuclei and a bland chromatin pattern (p<0.001). Scattered signet ring cells were helpful in suggesting ALK-positive adenocarcinoma (p<0.001).

Citations

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Machine learning‐based gene alteration prediction model for primary lung cancer using cytologic images
Shuhei Ishii, Manabu Takamatsu, Hironori Ninomiya, Kentaro Inamura, Takeshi Horai, Akira Iyoda, Naoko Honma, Rira Hoshi, Yuko Sugiyama, Noriko Yanagitani, Mingyon Mun, Hitoshi Abe, Tetuo Mikami, Kengo Takeuchi
Cancer Cytopathology.2022; 130(10): 812. CrossRef
Fine‐needle aspiration cytology of non‐small cell lung carcinoma: A paradigm shift
Pranab Dey, Ratan Kumar Ghosh
Diagnostic Cytopathology.2019; 47(4): 351. CrossRef
Qualitative and quantitative cytomorphological features of primary anaplastic lymphoma kinase‐positive lung cancer
Ryuko Tsukamoto, Hiroyuki Ohsaki, Sho Hosokawa, Yasunori Tokuhara, Shingo Kamoshida, Toshiko Sakuma, Tomoo Itoh, Chiho Ohbayashi
Cytopathology.2019; 30(3): 295. CrossRef
Primary signet-ring adenocarcinoma of the lung: A rare lung tumor
Varun Rajpal, Rahul Kumar Sharma, Charul Dabral, Deepak Talwar
South Asian Journal of Cancer.2019; 08(04): 257. CrossRef
Cytological features in eight patients with ALK‐rearranged lung cancer
Naoto Kuroda, Masahiko Ohara, Yukari Wada, Kaori Yasuoka, Keiko Mizuno, Kenji Yorita, Chiho Obayashi, Kengo Takeuchi
Diagnostic Cytopathology.2018; 46(6): 516. CrossRef
Cytological markers for predicting ALK‐positive pulmonary adenocarcinoma
K. Miyata, S. Morita, H. Dejima, N. Seki, N. Matsutani, M. Mieno, F. Kondo, Y. Soejima, F. Tanaka, M. Sawabe
Diagnostic Cytopathology.2017; 45(11): 963. CrossRef
ALK-rearranged adenocarcinoma with extensive mucin production can mimic mucinous adenocarcinoma: clinicopathological analysis and comprehensive histological comparison with KRAS-mutated mucinous adenocarcinoma
Yoon Jin Cha, Joungho Han, Soo Hyun Hwang, Tae Bum Lee, Hojoong Kim, Jea Ill Zo
Pathology.2016; 48(4): 325. CrossRef
Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine‐needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations
Dae Hyun Song, Boram Lee, Yooju Shin, In Ho Choi, Sang Yun Ha, Jae Jun Lee, Min Eui Hong, Yoon‐La Choi, Joungho Han, Sang‐Won Um
Diagnostic Cytopathology.2015; 43(7): 539. CrossRef
Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma
Seung Eun Lee, Boram Lee, Mineui Hong, Ji-Young Song, Kyungsoo Jung, Maruja E Lira, Mao Mao, Joungho Han, Jhingook Kim, Yoon-La Choi
Modern Pathology.2015; 28(4): 468. CrossRef

ERCC1 Predicts a Poorer Platinum-based Chemotherapy Outcome but a Better Outcome for Uracil-Tegafur in the Resected Stage I-II NSCLC.: Han Suk Ryu, Xianhua Xu, Hyojin Kim, Jong Suk Lee, Sanghoon Jheon, Jin Haeng Chung; Korean J Pathol. 2011;45(1):45-52.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.45

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Abstract PDF: BACKGROUND
The role of excision repair cross-complementation group 1 (ERCC1) has been controversial in non-small cell lung cancer (NSCLC) patients who received adjuvant chemotherapy with a platinum agent. We investigated ERCC1 expression in stage I-II NSCLC to clarify its significance for adjuvant chemotherapy.
METHODS
The ERCC1 expression profile was evaluated by immunohistochemistry and compared according to adjuvant chemotherapeutic agents in 146 patients who underwent surgical resection for stage I-II NSCLC. The patients were divided into 3 groups; adjuvant chemotherapy with a platinum based agent (18.5%, 27/146); adjuvant chemotherapy with uracil-tegafur (UFT) (40.4%, 59/146); surgery-alone (41.1%, 60/146).
RESULTS
Nuclear ERCC1 expression was detected in 71.9% (105/146) of NSCLC and was significantly associated with a shortened survival period in the group 1 patients who received the platinum based regimen after surgery. The group 2 patients who received UFT showed the longest survival period, followed by the surgery-alone group (overall survival, p=0.049; disease-free survival [DFS], p<0.001).
CONCLUSIONS
These results suggest that stage I-II NSCLC patients with ERCC1 expression experience a shorter DFS period with adjuvant chemotherapy with a platinum based regimen and may benefit from adjuvant chemotherapy with UFT, instead of platinum after surgery.

Relationship between the Endogenous Hypoxic Markers Hypoxia Inducible Factor-1alpha, Carbonic Anhydrase IX, and Epithelial Mesenchymal Transition Regulator TWIST Expression in Non-small Cell Lung Cancer.: Jung Hee Lee, Won Young Park, Seong Muk Jeong, Min Ki Lee, Young Dae Kim, Dong Hoon Shin, Chang Hun Lee; Korean J Pathol. 2010;44(5):469-476.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.469

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Abstract PDF

BACKGROUND
The epithelial mesenchymal transition (EMT) is intimately associated with tumor hypoxia. The present study was conducted to investigate the immunohistochemical relationship between hypoxic and EMT-related molecules in non-small cell lung carcinoma (NSCLC).
METHODS
Immunohistochemical staining for hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase (CA) IX, TWIST, and E-cadherin proteins was performed in 146 cases of NSCLC (80 cases of adenocarcinoma and 66 cases of squamous cell carcinoma) using tissue microarray blocks.
RESULTS
HIF-1alpha, TWIST, CA IX, and E-cadherin were expressed in 58 (40%), 90 (62%), 82 (56%), and 36 (25%) of 146 NSCLC cases, respectively. TWIST expression was positively correlated with HIF-1alpha expression (p = 0.03) and inversely correlated with E-cadherin expression (p < 0.01). TWIST and CA IX expression were not significantly interrelated, but each showed a relationship with histological tumor grade. However, the expression of these molecules had no significant effect on clinical staging or patient survival.
CONCLUSIONS
Although TWIST expression was correlated positively with HIF-1alpha expression and inversely correlated with E-cadherin, HIF-1alpha expression was not associated with E-cadherin expression. However, considering the relationship between HIF-1alpha and TWIST expression, further studies should be performed to demonstrate the role of hypoxia-induced EMT in NSCLC.

Citations

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Transcriptome analysis in gill reveals the adaptive mechanism of domesticated common carp to the high temperature in shallow rice paddies
Xiangbing Cheng, Fangcheng Li, Junjie Lu, Yuanlin Wen, Zhili Li, Jiayi Liao, Jiangwei Cao, Xumeng He, Jiamin Sun, Qigen Liu
Aquaculture.2024; 578: 740107. CrossRef
Clinicopathological and prognostic significance of Twist overexpression in NSCLC
Meng Li, Xing Zhang, Xiaoqing Xu, Jiubin Wu, Kaiwen Hu, Xiuwei Guo, Peitong Zhang
Oncotarget.2018; 9(18): 14642. CrossRef
The Role of TWIST in Ovarian Epithelial Cancers
Kyungbin Kim, Eun Young Park, Man Soo Yoon, Dong Soo Suh, Ki Hyung Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Kyung Un Choi
Korean Journal of Pathology.2014; 48(4): 283. CrossRef

Predictive Significance of KRAS and Tau for Chemoresponse in Advanced Non-Small-Cell Lung Cancer.: Jinyoung Yoo, Byoung Yong Shim, Chang Young Yoo, Seok Jin Kang, Kyo Young Lee; Korean J Pathol. 2009;43(5):435-440.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.435

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Abstract PDF

BACKGROUND
Taxane-platinum combinations are often used as first-line treatments for patients with advanced non-small cell lung cancer (NSCLC). Response to chemotherapy for these patients is still poor. The aim of our study was to investigate, for this disease, whether KRAS and Tau proteins affect responses to taxane-platinum combinations.
METHODS
Expression of KRAS and Tau was examined immunohistochemically in 71 tumor samples obtained from patients with stage IIIB or IV NSCLC prior to combination therapy. Expression was correlated with tumor responses.
RESULTS
The response rate was 55% (39 of 71). KRAS and Tau were expressed in seven (10%) and 31 (44%) patients, respectively. All seven KRAS-positive patients were non-responders (p=0.014). Among Tau-positive patients, 35% (11 of 31) responded to therapy, whereas a partial response was observed in 70% (28 of 40) of Tau-negatives (p=0.045). Two were positive for both, and they were non-responders. In patients negative for both, the response rate was 71% (25 of 35) (p=0.012).
CONCLUSIONS
Expression of KRAS and Tau are significantly correlated with poor responses to this combination therapy in advanced NSCLC patients, and may be a useful marker for chemoresistance.

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Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer
Stéphanie Papin, Paolo Paganetti
Brain Sciences.2020; 10(11): 862. CrossRef

Epidermal Growth Factor Receptor Expression of Non-small Cell Carcinoma and Its Relationship with Genomic Mutation.: Sang hee Seok, Mi Jin Kim; Korean J Pathol. 2008;42(2):94-99.

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Abstract PDF: BACKGROUND
It has recently been clarified that epidermal growth factor receptor (EGFR), which is a receptor tyrosine kinase of the erbB family, is abnormally activated in non-small cell lung carcinomas (NSCLC) and this fact is being utilized for creating targeted therapy. In this study, we aimed to identify the frequency of the EGFR expression and gene mutation in NSCLC, and to determine the correlation between them.
METHODS
Immunohistochemical staining for EGFR, C-erbB-2, cytokeratin 7, p53 and thyroid transcription factor-1, and EGFR mutation analysis were performed using paraffin-embedded archival tissue from 228 cases of NSCLC; this included 112 squamous cell carcinomas and 116 adenocarcinomas.
RESULTS
An EGFR expression and gene mutation occurred in 112 casees (53.5%) and 52 cases (22.8%), respectively. EGRF mutation was more frequent in the adenocarcinomas than in the squamous cell carcinomas, in non-smokers than in smokers, and in females than in males. EGFR mutation was significantly associated with an EGFR protein expression, and especially in adenocarcinomas.
CONCLUSION
The EGFR expression in NSCLC was associated with EGFR mutation, and especially in adenocarcinomas. More studies are needed to prove the clinical significance of the EGFR expression for creating targeted therapy to treat NSCLC.

Expressions of Cyclin E-pathway Proteins (cyclinE, cdk2, p21, p27, p57) and Their Prognostic Significance in Non-small Cell Lung Carcinomas.: Ji Han Jung, Gyeongsin Park, Myung Ah Lee, Jae Ho Byun, Chan Kwon Jung, Heejeong Lee, Kyo Young Lee, Sang In Shim, Chang Suk Kang; Korean J Pathol. 2006;40(1):24-31.

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Abstract PDF: BACKGROUND
The aberrant expression of cyclins, cdk and cdk inhibitor has been shown to be involved in oncogenic transformation. The aim of this study was to investigate the expression of the cyclin E-pathway proteins (cyclin E, cdk2, p21, p27, p57) in human non-small cell lung carcinomas (NSCLC) and also to evaluate the clinical significance of these expressions.
METHODS
A total of 203 consecutive patients with completely resected pathological stage I-III NSCLC were retrospectively reviewed. The expressions of cyclin E, cdk2, p21, p27 and, p57 was examined by performing immunohistochemistry with using the tissue microarray method.
RESULTS
In the total cases, the expression levels of cyclin E, cdk2, p21, p27 and p57 were 39.9% (81/203), 48.3% (98/203), 68.0% (138/203), 32.5% (66/203) and 2.7% (5/203), respectively. The overexpression of cyclin E and cdk2 was significantly and inversely correlated with the histologic differentiation in the adenocarcinoma (p<0.05), but not in the squamous cell carcinoma. Among the clinicopathologic factors, the stage and lymph node metastasis were associated with overall survival (p<0.05). Among these proteins, the negative expression of p21 was significantly correlated with a shortened survival rate (p<0.05).
CONCLUSIONS
These data suggest that the overexpression of cyclin E and cdk2 and the loss of p21 and p27 are associated with tumor progression in NSCLC. The aberrant expression of p21 is correlated with a poor prognosis. Therefore the immunohistochemical analysis of this protein as well as the clinical stage and, lymph node metastasis may be useful tools for evaluating the prognosis of NSCLC patients.

Expressions of CD44s Is Associated with the Expression of Cyclooxygenase-2 in Non-Small Cell Lung Cancers.: Sung Jig Lim, Hyun Jung Kim, Jung Yeon Kim, Kyeongmee Park; Korean J Pathol. 2006;40(1):17-23.

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Abstract PDF: BACKGROUND
The overexpression of Cox-2 in tumors is important for tumor invasion, angiogenesis, resistance to apoptosis and the suppression of host immunity. Moreover, a tumor's CD44 expression plays an important role in tumor invasion and metastasis. We examined the expression of COX-2 and also CD44 and its variants as well as the biological implications and relationship between Cox-2 and the CD44 variants in non-small cell lung carcinoma.
METHODS
The expressions of Cox-2 and also CD44s and its variants (CD44v3 and CD44v6) were examined by performing immunohistochemistry on 98 surgical specimens.
RESULTS
The expressions of CD44s, CD44v3 and CD44v6 were significantly more frequent in squamous cell carcinoma specimens than in the adenocarcinoma (CD44s, p=0.033; CD44v3, p=0.007; CD44v6, p=0.022). The loss of CD44s and CD44v3 were significantly correlated with poor tumor differentiation (CD44s, p=0.03; CD44v3, p=0.011). Patients with Cox-2 positive-adenocarcinoma tumors had a significantly worse cumulative survival than did those adenocarcinoma patients without the Cox-2 (p=0.048). The expression of Cox-2 was significantly associated with the CD44s expression in non-small cell lung cancer, and especially in squamous cell carcinoma.
CONCLUSIONS
These findings suggest that expression of CD44s is associated with the expression of Cox-2 in NSCLC, and especially squamous cell carcinoma.

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