Human epidermal growth factor receptor 2 (HER-2) status evaluation in advanced gastric cancer using immunohistochemistry versus silver in situ hybridization
Abstract:Accurate identification of human epidermal growth factor receptor 2 (HER-2) status in advanced gastric cancer patients is of utmost importance in terms of treatment planning. This study aimed to examine the HER-2 status in advanced gastric cancer patients using both immunohistochemistry (IHC) and silver in situ hybridization (SISH) techniques and to investigate concordance and diagnostic accuracy. In addition, associations between clinical parameters and HER 2 status were examined. A total of 313 patients diag… Show more
“…[6][7][8][9][10] The status of HER2 expression in gastric lesions is currently evaluated by immunohistochemistry (IHC), silver in situ hybridization (SISH), and fluorescence in situ hybridization (FISH). 5,11,12 It was found to be correlated with tumor grade and location on the intestine, but not with gender, age, tumor location or (tumor node metastasis) TNM stage, depth of invasion, lymph node metastases, and distant metastasis. 4,13 At present, gastroscopic biopsy is the main routine detection method to gain information about the histopathological characteristics of lesions before surgery.…”
These authors contributed equally to this workObjective: The aim of this study was to determine the role of contrast-enhanced computed tomography (CE-CT) parameters in predicting the expression status of HER2 in gastric adenocarcinoma (GAC) patients before radical gastrectomy. Materials and Methods: A total of 460 GAC patients who underwent non-contrast CT (NC-CT) and CE-CT examinations before radical resection were enrolled in this retrospective study. The radiologists reviewed their CT scans and recorded parameters, including CT attenuate value (CAV) and corrected CAV (cCAV). The pathologist identified the postoperative HER2 expression status, and HER2 expression status was evaluated by immunohistochemical staining (IHC). The association between CE-CT parameters and HER2 expression status was analyzed. Results: Among the 460 patients, 84 patients had HER2 over-expression status, at a prevalence of 18.3%. The CAVs were significantly different between the 2 different HER2 expression groups in the non-contrast and arterial phases (non-contrast phase: p = 0.005; arterial phase: p < 0.001). Besides, there was a significant difference in the cCAVs between the 2 groups in the arterial phase (arterial phase: p = 0.003). Univariate and multivariate logistic regression analyses identified that the maximum diameter of tumor, differentiation degree, CAV in non-contrast, arterial, and portal phases, and cCAV in the arterial phase were predictive factors of HER2 expression status. Conclusion: Our analyses showed that the CE-CT parameters were significantly different between different HER2 expression groups. CE-CT parameters could serve as simple, objective predictive factors of HER2 expression status of GAC patients.
“…[6][7][8][9][10] The status of HER2 expression in gastric lesions is currently evaluated by immunohistochemistry (IHC), silver in situ hybridization (SISH), and fluorescence in situ hybridization (FISH). 5,11,12 It was found to be correlated with tumor grade and location on the intestine, but not with gender, age, tumor location or (tumor node metastasis) TNM stage, depth of invasion, lymph node metastases, and distant metastasis. 4,13 At present, gastroscopic biopsy is the main routine detection method to gain information about the histopathological characteristics of lesions before surgery.…”
These authors contributed equally to this workObjective: The aim of this study was to determine the role of contrast-enhanced computed tomography (CE-CT) parameters in predicting the expression status of HER2 in gastric adenocarcinoma (GAC) patients before radical gastrectomy. Materials and Methods: A total of 460 GAC patients who underwent non-contrast CT (NC-CT) and CE-CT examinations before radical resection were enrolled in this retrospective study. The radiologists reviewed their CT scans and recorded parameters, including CT attenuate value (CAV) and corrected CAV (cCAV). The pathologist identified the postoperative HER2 expression status, and HER2 expression status was evaluated by immunohistochemical staining (IHC). The association between CE-CT parameters and HER2 expression status was analyzed. Results: Among the 460 patients, 84 patients had HER2 over-expression status, at a prevalence of 18.3%. The CAVs were significantly different between the 2 different HER2 expression groups in the non-contrast and arterial phases (non-contrast phase: p = 0.005; arterial phase: p < 0.001). Besides, there was a significant difference in the cCAVs between the 2 groups in the arterial phase (arterial phase: p = 0.003). Univariate and multivariate logistic regression analyses identified that the maximum diameter of tumor, differentiation degree, CAV in non-contrast, arterial, and portal phases, and cCAV in the arterial phase were predictive factors of HER2 expression status. Conclusion: Our analyses showed that the CE-CT parameters were significantly different between different HER2 expression groups. CE-CT parameters could serve as simple, objective predictive factors of HER2 expression status of GAC patients.
“…Human epidermal growth factor receptor 2 (HER-2), a member of the HER-2 family, is associated with an increased risk of recurrence and poor outcomes of certain malignancies, including breast and gastric cancer ( 13 ). HER-2 has been identified to be involved in cancer initiation and progression, and the dysregulation of HER-2 serves as an independent prognostic factor in gastric cancer ( 14 ). Thus, HER-2 is a common therapeutic target for gastric cancer.…”
Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR-204-5p in gastric cancer. The mRNA expression levels of miR-204-5p in gastric cancer were determined by reverse transcription-quantitative PCR. Cell proliferation was determined using Cell Counting Kit-8 and colony formation assays. Flow cytometry analysis was performed to detect the cell apoptosis rate. Wound healing and Transwell assays were carried out to determine the cell migration and invasion rates, respectively. A putative binding site of miR-204-5p in the 3′ untranslated region of human epidermal growth factor receptor 2 (HER-2) was predicted using a bioinformatics algorithm and confirmed using a dual-luciferase reporter assay. miR-204-5p levels were downregulated in gastric cancer cells. Overexpression of miR-204-5p significantly inhibited cell proliferation and decreased cell colony formation. Additionally, miR-204-5p decreased the migration and invasion rates of gastric cancer cells. Furthermore, an increased apoptotic rate was detected following overexpression of miR-204-5p, along with increased expression levels of Bax and decreased expression levels of Bcl-2. HER-2 was a direct target of miR-204-5p, and inhibition of HER-2 acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis, which was reversed by the inhibition of miR-204-5p expression. These results suggested that miR-204-5p could exert its anti-tumor function by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis via regulation of HER-2, which may be a potential therapeutic target for gastric cancer.
“…ERBB2, an oncogenic agent located in chromosome 17 (17q12–q21), encodes a 185-kDa transmembrane tyrosine kinase receptor (p185) [ 10 ]. ERBB2 has been identified to be implicated in cancerous initiation and progression, and its overexpression or amplification served as an independent prognostic factor in GC [ 11 ]. Furthermore, Tornillo et al revealed that ERBB2 overexpression activated the mammalian target of rapamycin (mTOR)/p70S6K signaling [ 12 ].…”
BackgroundIn recent years, the incidence of gastric cancer (GC) has been increasing worldwide. Emerging evidence shows that microRNAs (miRs) may be involved in the pathogenesis of GC. Thus, this study explored the mediatory role of miR-495 in GC chemosensitivity, and investigated the mechanism by which it affects the biological behaviors of GC cells via the mTOR signaling pathway.Material/MethodsAfter GC and paracancerous tissue collection, the positive rate of ERBB2 and mTOR was evaluated by immunohistochemistry. Subsequently, the expression of miR-495, ERBB2, and mTOR was determined by RT-qPCR and Western blot analysis. Next, the targeting relationship between miR-495 and ERBB2 was confirmed by dual-luciferase reporter gene assay. In addition, chemosensitivity and proliferation were detected by MTT assay and apoptosis was assessed by flow cytometry.ResultsWe found higher positive rates of ERBB2 and mTOR and decreased expression of miR-495 in GC tissues and showed that ERBB2 is the target gene of miR-495. Furthermore, we determined that overexpression of miR-495 and silencing of ERBB2 enhanced GC cell chemosensitivity and apoptosis, but inhibited GC cell proliferation. We also found that the effect of miR-495 inhibition was lost when ERBB2 was suppressed.ConclusionsThe key findings of our study demonstrate that the miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2. The study provides reliable evidence supporting the use of miR-495 as a novel potential target in the chemotherapy of GC.
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