Journal of Pathology and Translational Medicine

Original Articles

HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient: Dang Anh Thu Phan, Vu Thien Nguyen, Thi Ngoc Ha Hua, Quoc Dat Ngo, Thi Phuong Thao Doan, Sao Trung Nguyen, Anh Tu Thai, Van Thanh Nguyen; J Pathol Transl Med. 2017;51(4):396-402. Published online June 19, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.24

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Background
Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab.
Methods
We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated.
Results
In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+.
Conclusions
HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.

Citations

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Identifying HER2 from serum‐derived exosomes in advanced gastric cancer as a promising biomarker for assessing tissue HER2 status and predicting the efficacy of trastuzumab‐based therapy
Qian Li, Minzhi Lv, Lihua Lv, Nida Cao, Aiguang Zhao, Jiayan Chen, Xi Tang, Rongkui Luo, Shan Yu, Yan Zhou, Yuehong Cui, Wei Guo, Tianshu Liu
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Rafid A. Abood, Saad Alomar, Sawsan S. Alharoon
Journal of Public Health in Africa.2023; 14(9): 4. CrossRef
Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
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Cancers.2022; 14(15): 3750. CrossRef
Cell differentiation trajectory predicts patient potential immunotherapy response and prognosis in gastric cancer
Renshen Xiang, Yuping Rong, Yuhang Ge, Wei Song, Jun Ren, Tao Fu
Aging.2021; 13(4): 5928. CrossRef
Identification of stem cell-related subtypes and risk scoring for gastric cancer based on stem genomic profiling
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Stem Cell Research & Therapy.2021;[Epub] CrossRef
Oncogenic signaling pathways associated with immune evasion and resistance to immune checkpoint inhibitors in cancer
Yoshie Kobayashi, Seung-Oe Lim, Hirohito Yamaguchi
Seminars in Cancer Biology.2020; 65: 51. CrossRef
Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer
Yu-Chang Chuang, Hsin-Yi Wu, Yu-Ling Lin, Shey-Cherng Tzou, Cheng-Hsun Chuang, Ting-Yan Jian, Pin-Rong Chen, Yuan-Ching Chang, Chi-Hsin Lin, Tse-Hung Huang, Chao-Ching Wang, Yi-Lin Chan, Kuang-Wen Liao
Biological Procedures Online.2018;[Epub] CrossRef

EGFR Gene Amplification and Protein Expression in Invasive Ductal Carcinoma of the Breast: Won Hwangbo, Jeong Hyeon Lee, Sangjeong Ahn, Seojin Kim, Kyong Hwa Park, Chul Hwan Kim, Insun Kim; Korean J Pathol. 2013;47(2):107-115. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.107

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Abstract PDF

Background

The epidermal growth factor receptor (EGFR) is a surrogate marker for basal-like breast cancer. A recent study suggested that EGFR may be used as a target for breast cancer treatment.

Methods

A total of 706 invasive ductal carcinomas (IDC) of the breast were immunophenotyped, and 82 cases with EGFR protein expression were studied for EGFR gene amplification.

Results

EGFR protein was expressed in 121 of 706 IDCs (17.1%); 5.9% were of luminal type, 25.3% of epidermal growth factor receptor 2 (HER-2) type, and 79.3% of basal-like tumors. EGFR gene amplification and high polysomy (fluorescent in situ hybridization [FISH]-positive) were found in 18 of 82 cases (22.0%); 41.2% of the HER-2⁺, EGFR⁺, cytokeratin 5/6^- (CK5/6^-) group, 11.2% of the HER-2^-, EGFR⁺, CK5/6^- group, and 19.1% of the HER-2^-, EGFR⁺, CK5/6⁺ group. FISH-positive cases were detected in 8.3% of the EGFR protein 1⁺ expression cases, 15.9% of 2⁺ expression cases, and 38.5% of 3⁺ expression cases. In group 2, the tumors had a high Ki-67 labeling (>60%), but the patients showed better disease-free survival than those with tumors that co-expressed HER-2 or CK5/6.

Conclusions

EGFR-directed therapy can be considered in breast cancer patients with EGFR protein overexpression and gene amplification, and its therapeutic implication should be determined in HER-2 type breast cancer patients.

Citations

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Identification of a cross-talk between EGFR and Wnt/beta-catenin signaling pathways in HepG2 liver cancer cells
Gurjinder Singh, Md Mehedi Hossain, Aadil Qadir Bhat, Mir Owais Ayaz, Nasima Bano, Rafiqa Eachkoti, Mohd Jamal Dar
Cellular Signalling.2021; 79: 109885. CrossRef
Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer
Shailendra K. Gautam, Ranjana K. Kanchan, Jawed A. Siddiqui, Shailendra K. Maurya, Sanchita Rauth, Naveenkumar Perumal, Pranita Atri, Ramakanth C. Venkata, Kavita Mallya, Sameer Mirza, Moorthy P. Ponnusamy, Vimla Band, Sidharth Mahapatra, Maneesh Jain, Su
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Evaluation of lapatinib cytotoxicity and genotoxicity on MDA-MB-231 breast cancer cell line
Mona A.M. Abo-Zeid, Mahmoud T. Abo-Elfadl, Amira M. Gamal-Eldeen
Environmental Toxicology and Pharmacology.2019; 71: 103207. CrossRef
Improved characterization of the relationship between long intergenic non‐coding RNA Linc00152 and the occurrence and development of malignancies
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Relationship between EGFR expression and subcellular localization with cancer development and clinical outcome
Ge Yan, Mohamed E.M. Saeed, Sebastian Foersch, Jose Schneider, Wilfried Roth, Thomas Efferth
Oncotarget.2019; 10(20): 1918. CrossRef
A novel matrine derivative WM622 inhibits hepatocellular carcinoma by inhibiting PI3K/AKT signaling pathways
Xiao Sun, Xiao-bin Zhuo, Yi-ping Hu, Xuan Zheng, Qing-jie Zhao
Molecular and Cellular Biochemistry.2018; 449(1-2): 47. CrossRef
lncRNA LINC00152 knockdown had effects to suppress biological activity of lung cancer via EGFR/PI3K/AKT pathway
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Copy Number Profiling of MammaPrint™ Genes Reveals Association with the Prognosis of Breast Cancer Patients
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Evaluation of serum epidermal growth factor receptor (EGFR) in correlation to circulating tumor cells in patients with metastatic breast cancer
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EGFR Is Regulated by TFAP2C in Luminal Breast Cancer and Is a Target for Vandetanib
James P. De Andrade, Jung M. Park, Vivian W. Gu, George W. Woodfield, Mikhail V. Kulak, Allison W. Lorenzen, Vincent T. Wu, Sarah E. Van Dorin, Philip M. Spanheimer, Ronald J. Weigel
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Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer
H J Lee, A N Seo, E J Kim, M H Jang, Y J Kim, J H Kim, S-W Kim, H S Ryu, I A Park, S-A Im, G Gong, K H Jung, H J Kim, S Y Park
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Epidermal growth factor receptor protein overexpression and gene amplification are associated with aggressive biological behaviors of esophageal squamous cell carcinoma
GANG LIN, XIAO-JIANG SUN, QIAN-BO HAN, ZHUN WANG, YA-PING XU, JIA-LEI GU, WEI WU, GU ZHANG, JIN-LIN HU, WEN-YONG SUN, WEI-MIN MAO
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Immunohistochemical Classification of Primary and Secondary Glioblastomas
Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park
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A Comparison of Tumor Biology in Primary Ductal CarcinomaIn SituRecurring as Invasive Carcinoma versus a NewIn Situ
Wenjing Zhou, Christine Johansson, Karin Jirström, Anita Ringberg, Carl Blomqvist, Rose-Marie Amini, Marie-Louise Fjallskog, Fredrik Wärnberg
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Expression of c-Met Is Different along the Location and Associated with Lymph Node Metastasis of Head and Neck Carcinoma: Ji-Young Choe, Ji Yun Yun, Soo-Jeong Nam, Ji Eun Kim; Korean J Pathol. 2012;46(6):515-522. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.515

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Abstract PDF

Background

Activation of the c-Met pathway is involved in cancer progression and the prognosis. We aimed to identify any association of c-Met protein expression with a number of clinicopathologic variables including infection of human papillomavirus and Epstein-Barr virus (EBV) in head and neck carcinomas (HNCa).

Methods

Eighty-two cases were enrolled in this study. Expression of c-Met and p16 was investigated immunohistochemically. EBV was detected by in situ hybridization and amplification of the c-Met gene by fluorescence in situ hybridization.

Results

The c-Met protein was expressed in 41.5% (34/82), and gene amplification was found in 1.4% (1/71). High expression of c-Met was associated with the primary location of the tumor; the hypopharynx showed the highest expression, followed by the oral cavity, larynx, and nasal cavity. Squamous cell carcinoma expressed c-Met more frequently than undifferentiated carcinoma. Also, p16 immunoreactivity or EBV infection was associated with the tumor location and well-differentiated histologic type, but were not linked to c-Met expression. The patients with positive c-Met expression showed frequent lymph node metastasis.

Conclusions

Activation of the c-Met pathway might be involved in a subset of HNCa. Cases showing positive c-Met expression should be carefully monitored because of the high probability of lymph node metastasis.

Citations

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Case Report

HER2-Positive Breast Carcinomas with Co-amplification or Gain of Chromosome 17 Centromere Locus: Report of Three Cases and an Impact on HER2 Testing.: Hyeong Chan Shin, Young Kyung Bae, Aeri Kim, Seok Ju Park; Korean J Pathol. 2011;45(6):665-669.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.665

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Abstract PDF: Recently we experienced three cases of human epidermal growth factor receptor 2 (HER2)-amplified invasive breast carcinomas associated with co-amplification or gain of chromosome 17 centromere (CEP17) in silver-enhanced in situ hybridization (SISH) analysis. These cases revealed 2+ or 3+ staining for HER2 immunohistochemistry and >6 HER2 copies per cell on SISH analyses. However, the calculated HER2/CEP17 ratios were low (<2.2) and did not fit within the HER2-positive category. We interpreted those cases as HER2-positive tumors based on the number of HER2 copies per cell. There is a potential for misinterpretation of SISH analysis in cases showing increased CEP17 copy number, based on the criterion used for HER2 positivity (HER2 copies >6 per cell vs HER2/CEP17 ratio>2.2). We recommend reporting raw SISH or fluorescence in situ hybridization data, including number of cells counted, average numbers of HER2 and CEP17 signals, and the calculated HER2/CEP17 ratio to prevent underreporting of HER2 amplification.

Original Articles

Detection of the c-m c Oncogene Amplification in Ovarian Carcinomas by Differential Polymerase Chain Reaction.: Geun Shin Lyu, Chan Kum Park, Chun Geun Lee, Youl Hee Cho, Youn Yeoung Hwang, Jung Dal Lee; Korean J Pathol. 1997;31(7):644-654.

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Abstract PDF: The amplification of c-myc oncogene was evaluated in 42 cases of ovarian carcinomas to correlate with clinical parameters. Using oligonucleotide primers, sequences from the c-myc exon-3 gene and from a control gene, tissue plasminogen activator (tPA), were amplified simultaneously by polymerase chain reaction (PCR). After the products of differential PCR (d-PCR) were electrophoresed, slot blot hybridization was performed, and hybridized with P32 dATP-labeled myc and tPA oligonucleotide probes and then autoradiographed. The signal intensities of the two products were quantitated by densitometry and the ratios of two products (c-myc/tPA) were measured. The ovarian carcinomas showed significantly increased amplification of c-myc oncogene Oligonucleoti compared to normal control group (p<0.05). 15 of 42 cases (35.7%) showed various degrees of the MYC gene amplification up to 27 folds in various histologic types of ovarian carcinomas. No significant differences of the MYC gene amplification according to histologic subtypes, tumor action) grades and clinical stages of ovarian carcinomas were present.

Expression of Cellular Oncogenes in Gastric Carcinoma Related with Its Histologic Subtype: Southern blot analysis and immunohistochemistry.: Jin Sook Jeong, In Hoo Kim; Korean J Pathol. 1992;26(6):543-551.

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Abstract PDF: To search biologic characteristics of gastric carcinoma, one of the most common cancer in Korea, the author examined the alterations in DNA level and the expression of Ha-ras gene and c-myc gene in 20 primary tumors. Amplification of c-Ha-ras DNA was detected in 4(40%) of 10 patients who showed histologic subtype of relatively differentiated adenocarcinoma, but rearrangement of c-Ha-ras DNA was absent. Neither augumentation nor deletion of the c-myc DNA was observed. Higher expression of the ras p21 in tumor cells was noted in more differentiated tumor cells rather than poorly differentiated cases. One mucinous carcinoma, two signet ring cell carcinomas and one papillary carcinoma did not disclose expression of p21. The expressions of c-myc oncogene product were variable and were not correspond to the expressions of ras p21. A tendency that poorly differentiated tumor cells had higher expression of c-myc oncogene was suggested.

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