• Title, Summary, Keyword: HER-2

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Correlation between HER2 Overexpression and Clinicopathological Characteristics in Gastric Cancer Patients Who Have Undergone Curative Resection

  • Son, Ho Sung;Shin, Yeon Myung;Park, Kwang Kuk;Seo, Kyung Won;Yoon, Ki Young;Jang, Hee Kyung;Lee, Sang-Ho;Yang, Song I;Kim, Jeong Hoon
    • Journal of Gastric Cancer
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    • v.14 no.3
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    • pp.180-186
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    • 2014
  • Purpose: At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab ($Herceptin^{(R)}$; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection. Materials and Methods: A total of 139 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between October 2011 and March 2012 were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Results: The HER2+ rate was 15.1%. HER2 overexpression was associated with histological grade (P=0.044) and Lauren classification (P=0.036). There was no significant difference in the 2-year overall survival between HER2+ and HER2- patients (P=0.396). Multivariate analysis showed that HER2 was not an independent prognostic factor. Conclusions: HER2 overexpression in tumors was associated with histological grade and Lauren classification in gastric cancer patients with curative resection. However, HER2 was not an independent prognostic factor for gastric cancer in our study.

Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status

  • Payandeh, Mehrdad;Shahriari-Ahmadi, Ali;Sadeghi, Masoud;Sadeghi, Edris
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1015-1018
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    • 2016
  • Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ${\geq}10%$ positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also $Ki-67{\geq}20%$ as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ${\geq}20%$ in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-$67{\geq}20%$ had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.

Small Molecules Targeting for ESX-Sur2 Proteins' Interaction

  • Kwon, Young-Joo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • pp.77-86
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    • 2008
  • It's been known that overexpression of the oncoprotein Her2 (eu/ErbB2), transmembrane receptor protein, occurs in human breast cancer. Her2-positive breast cancer patients who have Her2 overexpression show less therapeutic efficacy with enhanced metathesis and increased resistance to chemotherapy. So far, a humanized monoclonal antibody against Her2 protein called Herceptin is the only drug approved by Food and Drug Administration for treatment of Her2-overexpressing breast tumors. However, antibody therapy of Herceptin may not be ideal method for therapeutic intervention of Her2 protein expression. The therapeutic intervention of Her2 protein expression may be more efficiently achieved by inhibiting the expression of Her2 gene rather than by down-regulating the Her2 protein already overexpressed. Here, we found that the interaction of two proteins of ESX (an epithelial-restricted transcription factor) and DRIP130/CRSP130/Sur2 (a Ras-linked subunit of human mediator complexes) mediates the expression of Her2 gene. The association of ESX with Sur2 is mediated by a small hydrophobic face of 8-amino acid helix in ESX, suggesting that the ESX-Sur2 interaction can be a new novel target for Her2-positive cancer. The process to develop potent ESX-Sur2 interaction inhibitors targeting for Her2-positive cancer therapeutics will be discussed.

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Development of a Quantitative ELISA for Anti HER-2 Antibodies using Human HER-2 Recombinant Proteins (인간 HER-2 재조합 단백질을 사용한 항 HER-2 항체 단백질의 ELISA 정량 방법 개발)

  • Jung, Sun-Ki;Ryu, Chang-Seon;Choung, Kyu-Jin;Song, Gyu-Yong;Kim, Sang-Kyum
    • YAKHAK HOEJI
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    • v.55 no.1
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    • pp.16-21
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    • 2011
  • HER-2 (Human Epidermal Growth Factor Receptor-2) is a protein giving higher aggressiveness in human breast cancers. Trastuzumab is a monoclonal antibody that targets HER-2 and is known to extend survival across all stages of HER2-positive breast cancer. In this study, we attempted to development of a quantitative ELISA (Enzyme-Linked ImmunoSorbent Assay) for evaluating anti HER-2 antibodies using human HER-2 recombinant proteins to support antibody producing processes and pharmacokinetic studies. We established direct or indirect ELISA method for the trastuzumab-like protein combined human recombinant HER-2. The ELISA method will prove to be great value in quantitating anti-HER-2 antibodies levels for developing anticancer antibodies.

Human Epidermal Growth Factor Receptor 2 Expression in Unresectable Gastric Cancers: Relationship with CT Characteristics

  • Lee, Jeong Sub;Kim, Se Hyung;Im, Seock-Ah;Kim, Min A;Han, Joon Koo
    • Korean Journal of Radiology
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    • v.18 no.5
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    • pp.809-820
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    • 2017
  • Objective: To retrospectively analyze the qualitative CT features that correlate with human epidermal growth factor receptor 2 (HER2)-expression in pathologically-proven gastric cancers. Materials and Methods: A total of 181 patients with pathologically-proven unresectable gastric cancers with HER2-expression (HER2-positive [n = 32] and negative [n = 149]) were included. CT features of primary gastric and metastatic tumors were reviewed. The prevalence of each CT finding was compared in both groups. Thereafter, binary logistic regression determined the most significant differential CT features. Clinical outcomes were compared using Kaplan-Meier method. Results: HER2-postive cancers showed lower clinical T stage (21.9% vs. 8.1%; p = 0.015), hyperattenuation on portal phase (62.5% vs. 30.9%; p = 0.003), and was more frequently metastasized to the liver (62.5% vs. 32.2%; p = 0.001), than HER2-negative cancers. On binary regression analysis, hyperattenuation of the tumor (odds ratio [OR], 4.68; p < 0.001) and hepatic metastasis (OR, 4.43; p = 0.001) were significant independent factors that predict HER2-positive cancers. Median survival of HER2-positive cancers (13.7 months) was significantly longer than HER2-negative cancers (9.6 months) (p = 0.035). Conclusion: HER2-positive gastric cancers show less-advanced T stage, hyperattenuation on the portal phase, and frequently metastasize to the liver, as compared to HER2-negative cancers.

Association of High LDH and Low Glucose Levels in Pleural Space with HER2 Expression in Non-Small Cell Lung Cancer

  • Ziaian, Bijan;Saberi, Ali;Ghayyoumi, Mohammad Ali;Safaei, Akbar;Ghaderi, Abbas;Mojtahedi, Zahra
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1617-1620
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    • 2014
  • Background: Evidence shows direct link of HER2 to increased glycolysis and over production of lactate dehydrogenase (LDH). HER2 overexpression, high LDH and low glucose pleural levels are associated with poor prognosis in lung cancer. Here, their relationships were investigated. Materials and Methods: HER2 positivity was studied using immunohistochemistry in non-small cell lung cancer. Glucose and LDH levels were measured using commercial colorimetric kits. Results: Of 42 patients (29 adenocarcinoma and 13 squamous cell carcinoma), 28 (66.7%) were HER2-negative, 14 (33.3%) were HER2- positive, including 9 (21.4%) weakly stained (1+) and 5 (11.9%) moderately stained (2+) samples. The relationship between HER2 and glucose and LDH levels were tested in 20 newly diagnosed lung cancer patients who had simultaneous pleural and serum samples. Pleural and serum LDH levels were increased, and pleural glucose levels were decreased with the scale of HER2 positivity, and that the difference in glucose levels between HER2-negative group and HER2-positive patients scored at 2+ reached statistical significance (p=0.02). This latter group all had pleural glucose levels below 40 mg/dl. Conclusions: For the first time, we showed a significant association between low pleural glucose level and overexpression of HER2 in lung cancer. Further investigations are warranted to disclose the association of HER2 with low pleural glucose levels in other populations, with a larger sample size, in malignant pleural effusions caused by other types of cancer, and finally to assess employment as a screening tool for finding HER2-positive cases of lung cancer.

Possible Role of HER-2 in the Progression of Prostate Cancer from Primary Tumor to Androgen Independence

  • Murray, Nigel P;Reyes, Eduardo;Fuentealba, Cynthia;Jacob, Omar;Orellana, Nelson
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6615-6619
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    • 2015
  • Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.

Breast Cancer Subtypes Identified by the ER, PR and HER-2 Status in Thai Women

  • Chuthapisith, Suebwong;Permsapaya, Watthanasak;Warnnissorn, Malee;Akewanlop, Charuwan;Sirivatanauksorn, Vorapan;Osoth, Poramaporn Prasarttong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.459-462
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    • 2012
  • Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2 +), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, ${\chi}^2$). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, ${\chi}^2$). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, ${\chi}^2$). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.

Expression of Human Epidermal Growth Factor Receptor (Her 2/neu) and Proliferative Marker Ki-67: Association with Clinicopathological Parameters in Gallbladder Carcinoma

  • Pujani, Mukta;Makker, Isha;Makker, Annu;Goel, Madhu Mati;Jetley, Sujata
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3903-3909
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    • 2016
  • Purpose: To evaluate the expression of Her2/neu and Ki-67 in benign and malignant gallbladder lesions, and to establish correlations with clinico-pathologic parameters. Materials and Methods: A retrospective analysis was conducted on formalin fixed paraffin embedded (FFPE) benign (n=25) and malignant gallbladder (n=25) tissue samples. Hematoxylin and eosin stained slides of each case were reviewed for: type of malignancy (whether adenocarcinoma, squamous cell carcinoma, or any other type), grade (well, moderate, and poor), depth of invasion, pre-neoplastic changes in adjacent mucosal epithelium like metaplasia and dysplasia. Immunohistochemistry for Her 2 neu and Ki-67 was performed and data analysis was conducted using SPSS 17 software. Chi-square test was used to compare categorical/dichotomous variables. P value of ${\leq}0.05$ was considered significant. Results: The difference of Her 2 neu expression and Ki67 index between benign and malignant groups was found to be statistically significant. Her2/neu positivity did not have any significant correlation with various clinicopathological parameters other than liver involvement. 5 cases of gallbladder cancer showed both Her2/neu and Ki67 positivity. Ten cases were Ki67 positive but Her2/neu negative while one case was Her2/neu positive but Ki67 negative. Conclusions: The present study demonstrated overexpression of Her2/neu and Ki67 in gallbladder cancer. A trend of decreasing Her2/neu expression with increasing grade of tumor was observed. Furthermore, greater Ki67 positivity was found in cases with lymph node metastasis and distant metastasis. Future studies with a larger number of patients will be required to precisely define the correlation of Her2/neu expression and Ki67 positivity with clinicopathological parameters. The results however are encouraging and suggest evaluation of Her2/neu as a candidate for targeted therapy.

Impact of HER2 and PTEN Simultaneous Deregulation in Non-small Cell Lung Carcinoma: Correlation with Biological Behavior

  • Panagiotou, Ioannis;Georgiannos, Stavros N.;Tsiambas, Evangelos;Karameris, Andreas;Konstantinou, Marios;Lazaris, Andreas C.;Kavantzas, Nikolaos;Vilaras, George;Patsouris, Efstratios
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6311-6318
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    • 2012
  • Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.