Journal of Pathology and Translational Medicine

Original Articles

Differential MicroRNA Expression between EGFR T790M and L858R Mutated Lung Cancer: Ji Yeon Kim, Woo Jeong Lee, Ha Young Park, Ahrong Kim, Dong Hoon Shin, Chang Hun Lee; J Pathol Transl Med. 2018;52(5):275-282. Published online August 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.29

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Background
MicroRNAs (miRNAs) are short, non-coding RNAs that mediate post-transcriptional gene regulation. They are commonly deregulated in human malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to investigate miRNA expression in T790M-mutated NSCLC resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.
Methods
Six cases of resected NSCLC harboring the T790M mutation were examined. We performed miRNA time polymerase chain reaction (PCR) array profiling using EGFR T790M-mutated NSCLC and L858R-mutated NSCLC. Once identified, miRNAs that were differentially expressed between the two groups were validated by quantitative real-time polymerase chain reaction (qRT-PCR).
Results
miRNA PCR array profiling revealed three up-regulated miRNAs whose expression levels were altered 4.0-fold or more in the EGFR T790M mutation group than in the L858R group: miR-1 (fold change, 4.384), miR-196a (fold change, 4.138), and miR-124 (fold change, 4.132). The three differentially expressed miRNAs were validated by qRT-PCR, and they were found to be overexpressed in the T790M group relative to L858R group. In particular, expression levels of miR-1 and miR-124 were significantly higher in the T790M group (p-value of miR-1 = .004, miR-124 = .007, miR-196a = .096).
Conclusions
MiR-1, miR-124, and miR-196a are overexpressed in EGFR T790M mutated NSCLC.

Citations

Citations to this article as recorded by

Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages
Hao Ho, Sung-Liang Yu, Hsuan-Yu Chen, Shin-Sheng Yuan, Kang-Yi Su, Yi-Chiung Hsu, Chung-Ping Hsu, Cheng-Yen Chuang, Ya-Hsuan Chang, Yu-Cheng Li, Chiou-Ling Cheng, Gee-Chen Chang, Pan-Chyr Yang, Ker-Chau Li
Lung Cancer.2023; 184: 107352. CrossRef
Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
Alessandro Leonetti, Mjriam Capula, Roberta Minari, Giulia Mazzaschi, Alessandro Gregori, Btissame El Hassouni, Filippo Papini, Paola Bordi, Michela Verzè, Amir Avan, Marcello Tiseo, Elisa Giovannetti
Cells.2021; 10(6): 1520. CrossRef
Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line
Nalini Devi Verusingam, Yi-Chen Chen, Heng-Fu Lin, Chao-Yu Liu, Ming-Cheng Lee, Kai-Hsi Lu, Soon-Keng Cheong, Alan Han-Kiat Ong, Shih-Hwa Chiou, Mong-Lien Wang
Journal of the Chinese Medical Association.2021; 84(3): 248. CrossRef
Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands
Sarah Sayed Hassanein, Sherif Abdelaziz Ibrahim, Ahmed Lotfy Abdel-Mawgood
International Journal of Molecular Sciences.2021; 22(22): 12496. CrossRef
The Roles of MicroRNA in Lung Cancer
Kuan-Li Wu, Ying-Ming Tsai, Chi-Tun Lien, Po-Lin Kuo, Jen-Yu Hung
International Journal of Molecular Sciences.2019; 20(7): 1611. CrossRef

Clinicopathologic Significances of EGFR Expression at Invasive Front of Colorectal Cancer.: Yeo Ju Kang, Chan Kwon Jung, Yeong Jin Choi, Kyo Young Lee, Hyung Jin Kim, Won Kyung Kang, Seong Taek Oh; Korean J Pathol. 2010;44(1):16-21.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.16

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Abstract PDF: BACKGROUND
Epidermal growth factor receptor (EGFR) is frequently expressed in the invasive front of colorectal cancer (CRC), but its clinicopathologic significance remains unclear. We investigated the clinical value of the EGFR expression at the invasive front of CRC.
METHODS
We performed an immunohistochemical analysis in order to examine the expression and distribution of EGFR in 214 cases of CRC. The EGFR status was considered positive when > or =1% of the tumor cells had membranous staining.
RESULTS
Overall, an EGFR expression was observed in 144 (67%) cases and it had no significant relationship with the clinicopathologic parameters. However, an EGFR expression at the invasive front was correlated with lymphatic invasion, lymph node metastasis and a high level of serum carcinoembryonic antigen (p = 0.028, p = 0.043, and p = 0.045, respectively). For the budding-positive CRCs liver metastases were found in the cases with an EGFR expression at the budding, but no liver metastasis occurred in the EGFR negative cases at the budding (p = 0.030).
CONCLUSIONS
An EGFR expression at the invasive front has clinicopathologic significances in patients with CRC. An EGFR expression at tumor cell budding is a pathologic marker that suggests the high potential for liver metastasis in CRC.

Expression of Epidermal Growth Factor Receptor and Transforming Growth Factor-beta1 Type II Receptor in Oral Leukoplakia and Squamous Cell Carcinoma.: Tae Yeon Kim, Jong In Yook, Jin Kim; Korean J Pathol. 1997;31(12):1247-1255.

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Abstract PDF: Growth stimulatory/inhibitory factors and their receptors are the important mediators of control of epithelial cell proliferation and differentiation. The aim of this study was to observe the distribution of epidermal growth factor receptor (EGFR) and transforming growth factor-beta1 type II receptor (TbetaRII) during carcinogenesis of oral squamous cell carcinoma (OSCC). Formalin fixed, paraffin embedded tissue from 25 oral leukoplakias (OL) and 15 OSCC was immunostained by avidin-biotin complex method. In OSCC, the carcinomatous area and the adjacent dysplastic/ hyperplastic area were examined. In OL, the hyperplasia and the epithelial dysplasia were examined. Monoclonal anti-EGFR Ab and polyclonal anti-TbetaRII Ab were applied. EGFR was mainly expressed in the basal layer and was increased with epithelial dysplasia in OL. TbetaRII was not detected in the basal cell layer and dysplastic area in OL. In contrast, the dysplastic area adjacent to OSCC showed positivity in the entire layer including the dysplastic area. In all cases of OSCC, both EGFR and TbetaRII showed positive reactions. EGFR was increased with the progression to the malignancy, and the expression pattern of TbetaR II was altered to be positive in the basal cell layer with progression to malignancy. These results suggest that the expression of EGFR appeared to be an early event and TbetaR II may be related to malignant transformation during oral carcinogenesis. The expression pattern of EGFR and TbetaR II may contribute to predict the risk of the development of carcinoma in oral premalignant lesions.

Protein Expression and Gene Amplification of Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer: Correlation with the Response to Gefitinib Therapy.: Jinyoung Yoo, Kyungji Lee, Ji Han Jung, Byoung Yong Shim, Sung Hwan Kim, Deog Gon Cho, Myeong Im Ahn, Chi Hong Kim, Kyu Do Cho, Hoon Kyo Kim, Seok Jin Kang; Korean J Pathol. 2008;42(1):1-8.

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Abstract PDF: BACKGROUND
Gefitinib is an EGFR tyrosine kinase inhibitor that has shown dramatic effectiveness in a subset of non-small cell lung cancer (NSCLC) patients. We evaluated the response rate to gefitinib, and the significance of the EGFR and HER2/neu status as predictive markers of the tumor response.
METHODS
The EGFR and HER2/neu protein expressions, as determined by immunohistochemistry (IHC) and gene amplification via chromogenic in situ hybridization (CISH), were analyzed in biopsy specimens from 46 patients with advanced NSCLC. After their failure with the first-line treatment, all the patients had received gefitinib treatment.
RESULTS
A partial response (PR) was achieved in 8 patients (17.4%). An EGFR overexpression was detected in 80.4% (37/46) of the tumors, and this was observed exclusively in patients with a PR (100% vs 75.3%, respectively; p=0.076). EGFR gene amplification was present in 47.8% of the tumors (22/46). HER2/neu was overexpressed in 13%(6/46) and it was amplified in 17% (7/46). The overall survival was prolonged in the female patients (p=0.007), and in patients with T1 and T2 disease (p=0.039), adenocarcinoma (p=0.010), a PR (p=0.022), an EGFR IHC+ status (p=0.033), an EGFR IHC+/CISH+ status (p=0.010), or an EGFR+/HER2/neu+ status (p=0.030). On multivariate analysis, gender, T disease and EGFR IHC/CISH remained the significant predictors of survival.
CONCLUSIONS
Gefitinib showed a modest effect for the patients with chemotherapy-refractory advanced NSCLC. A combination of EGFR IHC and CISH might be important for identifying those patients who are most likely to benefit from gefitinib therapy.

In Situ mRNA Hybridization and an Immunohistochemical Study of EGFR in Uterine Cervix Cancer.: Hyang Mi Ko, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1995;29(3):343-351.

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Abstract PDF: Epidermal growth factor receptor (EGFR) is an intergral membrane protein. Overexpression or mutation of EGFR may play a role in careinogenesis. Recently, many molecular biologic techniques have been used to study expression of oncogenes. One of them, in situ mRNA hybridization, using paraffin embedded blocks, offers a unique means to allow precise localization within histological preparations, and also overcomes problems relating to translation defects and abnormal translation. In order to confirm the usefulness of epidermal growth factor receptor as a tumor marker, and to compare the expression of EGFR between in situ MRNA hybridization and an immunohistochemical study, in situ MRNA hybridization was performed along with an immunohistochemical study for EGFR in paraffin sections of 84 uterine cervix carcinomas. A positive reaction for EGFR was observed mairdy in the cytoplasm of tumor cells. The vascular muscle layer and uterine muscle tissue around the cancer nest revealed a positive reaction in immunohistochemical stain for EGFR, with a negative reaction for EGFR mRNA. In the cancer nests, the immunohistochemical positive reaction for EGFR was strong in differentiated cells and keratin pearls, but a strong positive reaction for EGFR mRNA was localized in undifferentiated cells. The overall positive of immunostaing for EGFR was 77% for uterine cervix carcinoma; 71 % for carcinoma in situ, 71 % for microinvaseve carcinoma, and 89% for invasive carcinoma. The overall positivity of EGFR from in situ MRNA hybridization was 94% of the uterine cervix carcinoma; 93% for carcinoma in situ, 93% for microinvasive carcinoma, and 96% for invasive carcinoma. From these results, EGFR is a useful tumor marker for uterine cervix carcinoma, and in situ mRNA hybridization has greater sensitivity and specificity than immunohistochemistry.

An Immunohistochemical Study for the neu and ras Oncoprotein and Epidermal Growth Factor Receptor in the Breast Carcinoma.: Jeong Ja Park, Tae In Park, Tae Joong Sohn, In Soo Suh; Korean J Pathol. 1994;28(2):126-134.

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Abstract PDF: To evaluate correlation between the expression of neu and ras oncoprotein and epidermal growth factor receptor on breast carcinoma and other known prognostic factors, immunohisto-chemical studies were performed. Positive reaction for neu, which appeared as brown granular deposits along cell surface and cytoplasm of the tumor cells, was significantly correlated with the histological grade but not with other prognostic factors such as tumor size, lymph node me-tastasis, local recurrence, and estrogen and progesteron receptor status. Also granular deposits of ras were noted in the carcinoma cells in the cytoplasm, while the epithelaial cells of the normal lobule and duct showed negative reation. But expression of ras was not significantly associated ras with other prognostic factors. The reaction for EGFR was mostly negative on epithelial cells of both the normal lobule and duct, and was not significantly associated with other prognostic factors. The results suggested that expression of the neu oncoprotein is significantly associated with the histological grade of breast carcinoma, while the ras and the EGFR do not show significant prognostic value.

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