Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival.

The prognostic role of epidermal growth factor receptor (EGFR) and HER2-neu remains controversial in patients with non-small cell lung cancer (NSCLC). We studied the association between the mRNA expression of EGFR, HER2-neu, and survival in primary tumor and matching nonmalignant tissues from 83 patients with NSCLC. Analysis was performed using a quantitative real-time PCR system (Taqman). EGFR and HER2-neu mRNA expression was detectable in all (100%) specimens analyzed. Twenty-nine (34.9%) patients had high HER2-neu expression, and 28 (33.7%) patients had high EGFR expression. A high HER2-neu and EGFR coexpression was detectable in 14 (16.9%) patients. High HER2-neu expression was associated with inferior survival (P = 0.004), whereas high EGFR expression showed a trend toward inferior survival (P = 0.176). The impact of HER2-neu and EGFR coexpression on patients' survival was additive (P = 0.003). Multivariate analysis determined high HER2-neu expression (P = 0.041), and high EGFR/HER2-neu coexpression (P = 0.030) as significant and independent unfavorable prognostic factors. These findings indicate that HER2-neu and EGFR play a crucial role in the biological behavior of NSCLCs. Testing of molecular marker coexpression (EGFR and HER2-neu) improves the estimation of prognosis and appears to define low- and high-risk groups for treatment failure in curatively resected NSCLC.     

Immuno-Histochemical Assessment of HER2NEU Expression in Gastric Adenocarcinoma in North Karnataka,India

Background and Objectives: Gastric cancer is the fourth most common cancer worldwide and ranks fifth in India.Surgical resection is curative in early stage gastric cancers. Most of the gastric cancers are diagnosed at an advancedstage necessitating multimodality treatment strategies. Based on the ToGA trial, the international regulatory agencieshave recently approved trastuzumab in locally advanced and metastatic gastric and gastroesophageal adenocarcinomasexpressing HER2. Since there are limited studies from India and no published data available from this part of NorthKarnataka, we undertook this study to evaluate the frequency of expression of HER2 in gastric and gastroesophagealadenocarcinomas and to correlate it with various clinicopathological variables. Methodology: The study was conductedin the Department of Pathology, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka from May 2012to January 2016. The samples included both endoscopic biopsies and gastrectomies. Histopathological slides from 70cases were reviewed. Immunohistochemical staining for HER2 was performed in all the cases and Hoffman’s gastriccancer scoring system was employed. The results of HER2 expression was correlated with various clinicopathologicalparameters. Results: HER2 positivity was seen in 16/70 cases (23%). 6 cases (8.5%) were equivocal and 48/70 cases(68.5%) were HER2 negative. HER2 positivity was more common in GEJ cancers and intestinal type of adenocarcinoma.However, it did not correlate with age, gender, grade and stage. Conclusion: HER2 positivity was noted in 23% of thecases. 23.4% of intestinal type and 21.7% of diffuse type were HER2 positive. HER2 positivity did not significantlydepend on age, gender, tumour type, grade and stage. Hence, HER2 remains as an independent biomarker and should betested in all patients of gastric cancer regardless of the clinicopathological findings for offering a personalized treatment.     

Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer.

PURPOSE: Recent studies have indicated that expression of chemokine receptors CXCR4 and CCR7 could be an indicator of the metastatic potential of breast cancer. Expression of CXCR4 and CCR7 along with the biomarkers HER2-neu and epidermal growth factor receptor (EGFR) was investigated in inflammatory breast cancer (IBC) to evaluate their prognostic implications. EXPERIMENTAL DESIGN: CXCR4, CCR7, and EGFR were evaluated by immunohistochemical staining (IHC) of paraffin-embedded tissue sections. HER2-neu amplification was assessed by FISH and/or IHC. All patients received chemotherapy, surgery, and radiation. RESULTS: Forty-four cases diagnosed with IBC from 1994 to 2002 were included in the study. In all, 18 (40.9%) patients had positive CXCR4, 10 (22.7%) had positive CCR7, 21 (47.7%) had positive HER2-neu, and EGFR was positive in 12 of 40 patients (30%). The 5-year overall survival (OS) was 24.8% for CXCR4-positive disease versus 42.3% for CXCR4-negative patients (P = 0.53) and 20.0% for CCR7-positive disease versus 41.9% for CCR7-negative patients (P = 0.24). EGFR-positive disease had significantly worse OS compared with EGFR-negative disease (P = 0.01). CONCLUSIONS: These data demonstrate the expression of growth factor and chemokine receptors in IBC. The expression of these receptors is associated with increased risk of recurrence and death, and thus, they may represent potential therapeutic targets in IBC.     

Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

Objective: Human epidermal growth factor receptor 2 (erbb2/HER2) overexpression, has now been implicatedin advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-EastIndia and to assess the impact of various demographic and clinical parameters on HER2 positivity. Methods: A total of68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examinationfrom September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational(epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved,standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters.Results: The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantlyhigher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patientswith well differentiated histology and was more common in patients with stage II and III diseases, but neither of theassociations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours(56% versus 44%, P=0.002). Conclusion: HER2 overexpression was evident in 56% of the North-East Indian patientswith locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlatedsignificantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expressionis recommended to provide a therapeutic advantage in Indian patients.     

Prognostic Value of PD-L1 Immunohistochemical Marker in Gastric Carcinoma and Its Correlation with HER2 Status

Objective: Programmed death-ligand 1 (PD-L1) and human epidermal growth factor receptor 2 (HER2) are currently considered as prognostic markers and therapeutic targets in many human cancers. This study aims to evaluate immunohistochemical (IHC) expression of PD-L1 in gastric cancer (GC) and explore its prognostic role in terms of association with HER2 expression, different clinico-pathological variables, in particular density and cluster designation (CD)8 positivity in tumor infiltrating lymphocytes (TILs) and with patients’ disease-free and overall survival (DFS, OS). Methods: This retrospective cohort study included 111 diagnosed primary GC patients who underwent surgical resection at the Gastrointestinal Surgery Center (GISC), Faculty of Medicine, Mansoura University, Egypt. After demographic, clinicopathological and survival data collection, histopathological evaluation was done for GC typing, staging and assessment of the histopathological prognostic parameters. IHC was performed for PD-L1, HER2 and CD8. PDL-1 was scored using the Combined Positive Score (CPS). Results: PD-L1 was expressed in 43.2% of GCs at a CPS cut-off value ≥ 1. PDL-1 positivity was significantly associated with high TILs and CD8+ TILs (p=0.008, 0.016 respectively), indicating its contribution to tumor microenvironment along with the TILs. Multivariate analysis spotted PD-L1 positivity as an independent prognostic predictor for shorter OS in GC (p=0.013), with a tendency toward shorter DFS. Only 9.9% GCs were HER2 positive (score +3) with no significant association with PD-L1. Conclusion: PDL-1 is a promising prognostic and therapeutic target in GC that may direct the selection of patients for immunotherapy and checkpoint-blockade (pembrolizumab) therapy.     

CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer.

PURPOSE: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metastasis. We therefore studied the differential expression of CCR7 and CXCR4, along with that of the biomarker HER2-neu, to evaluate whether these biomarkers could predict axillary lymph node metastasis in breast cancer. EXPERIMENTAL DESIGN: Biomarker expression levels were evaluated using paraffin-embedded tissue sections of lymph node-negative (n = 99) and lymph node-positive (n = 98) T1 breast cancer by immunohistochemical staining. RESULTS: Lymph node-positive tumors showed higher rates of high cytoplasmic CCR7 staining (21.5% versus 8.5%, P = 0.013) and HER2-neu overexpression (21.5% versus 9.3%, P = 0.019) than did lymph node-negative tumors. Similarly, high cytoplasmic CXCR4 expression occurred more commonly in lymph node-positive tumors (11.2% versus 5.1%, P = 0.113). In contrast, predominantly nuclear CXCR4 staining was more likely to be found in lymph node-negative tumors (54.5% versus 37.8%, P = 0.018). Furthermore, cytoplasmic CXCR4 coexpressed with HER2-neu was the only factor associated with involvement of four or more lymph nodes (16.7% versus 1.2%, P = 0.04) among lymph node-positive tumors. When all three biomarkers (CCR7, CXCR4, HER2-neu) were utilized together, 50.0% of lymph node-positive tumors highly expressed one of these biomarkers compared with 18.8% of the lymph node-negative tumors (P < 0.0001). CONCLUSIONS: Our results suggest that the chemokine receptor CCR7 is a novel biomarker that can predict lymph node metastases in breast cancer. Utilization of additional markers, such as CXCR4 and HER2-neu, further improves the prediction of the presence and extent of lymph node involvement.     

Correlation between HER2 Expression and Clinicopathological Features of Breast Cancer: A Cross- Sectional Study in Vietnam

Background: HER2 is the target of the therapeutic agents which are used to treat HER2-positive breast cancer. Reports have shown that the HER2 oncogene expression and its association with clinicopathological factors remain unclear in breast cancer (BC) patients.  This study aimed to determine the correlation between HER2 expression and clinicalpathological characteristics of breast cancer in Vietnamese women. Methods: Between June 2016 and August 2018, paraffin-embedded specimens from 237 patients with primary invasive breast carcinoma in Hue University Hospital and Hue Center Hospital, Hue city, Vietnam were examined for pathological features. The gene expression of HER2, ER, PR and Ki-67 were determined by immunohistochemistry (IHC). The gene amplification of Her2 was assessed by using Dual color in situ hybridization (DISH). Results: The most frequent histological type was invasive carcinoma of no special type (NST) with 77.35%, the highest percentage of patients with Grade II was detected (59.36%), tumor size > 2 cm accounted for 71.31% of cases, Lymph node metastases were available in 57.86% cases. Most patients were diagnosed at stage II (59.18%). The majority of patients were classified as moderate Nottingham prognostic index (54.9%). Estrogen receptor and Progesterone receptor were positive in 53.16% and 50.63%, respectively. 76.37% of cases were in high expression group of Ki-67 (≥14%). HER2 IHC 2+, 3+ were accounted for 28.69% and HER2 gene amplification was detected in 31% cases. HER2 gene amplification and/or overexpression was significantly associated with cell proliferation index Ki67. Furthermore, HER2 gene expression tended to be more frequently found in tumors with large tumor size, high grade, high stage and high Nottingham prognostic index and confirmed their prognostic independent role. Conclusions: Our data indicated that HER2 gene expression was significantly correlated with cell proliferation index Ki67, but not significantly associated with another clinicopathological factors in breast cancer of Vietnamese women.     

Targeted therapies in gastroesophageal cancer

Gastroesophageal cancers comprising gastric cancer (GC), and cancers of the distal oesophagus and gastroesophageal junction (GEJ) are a global health threat. In Western populations the incidence of GC is declining which has been attributed to effective strategies of eradicating Helicobacter pylori infection. To the contrary, GEJ cancers are on the rise, with obesity and reflux disease being viewed as major risk factors. During the past decade perioperative chemotherapy, pre- or postoperative radio-chemotherapy, and, in Asian populations, adjuvant chemotherapy have been shown to improve the outcome of patients with advanced GC and GEJ cancers suited for surgery. Less progress has been made in the treatment of metastatic disease. The introduction of trastuzumab in combination with platinum/fluoropyrimidine-based chemotherapy for patients with HER2-positive disease has marked a turning point. Recently, several novel agents targeting growth factor receptors, angiogenic pathways, adhesion molecules and mediators of intracellular signal transduction have been clinically explored. Here we summarise the current status and future developments of molecularly targeted therapies in GC and GEJ cancer.     

The multigene classifiers 95GC/42GC/155GC for precision medicine in ER-positive HER2-negative early breast cancer

In clinical decision-making, to decide the indication for adjuvant chemotherapy for estrogen receptor-positive (ER+), human epidermal growth factor receptor-2-negative (HER2−), and node-negative (n0) breast cancer patients, the accurate estimation of recurrence risk is essential. Unfortunately, conventional prognostic factors, such as tumor size, histological grade and ER, progesterone receptor (PR), and HER2 status as well as Ki67 index, are not sufficiently accurate for such estimation. Therefore, several multigene assays (MGAs) based on the mRNA expression analysis of multiple genes in tumor tissue have been developed to better predict patient prognosis. These assays include Oncotype DX, MammaPrint, PAM50, GGI, EndoPredict, and BCI. We developed Curebest™ 95-Gene Classifier Breast (95GC) classifier, which is unique in that mRNA expression data of all 20 000 human genes are secondarily obtainable, as the 95GC assay is performed using Affymetrix microarray. This can capture mRNA expression of not only 95 genes but also every gene at once, and such gene expression data can be utilized by the other MGAs that we have developed, such as the 155GC, which is used for the prognostic prediction of ER+/HER2− breast cancer patients treated with neoadjuvant chemotherapy. We also developed the 42GC for predicting late recurrence in ER+/HER2− breast cancer patients. In this mini-review, our recent attempt at the development of various MGAs, which is expected to facilitate the implementation of precision medicine in ER+/HER2− breast cancer patients, is presented with a special emphasis on 95GC.     

Flotillin-2在胃癌组织中的表达及其临床意义

[摘要] 目的：检测脂筏标记蛋白-2(Flotillin-2,Flot-2)在胃癌组织中的表达水平,分析Flot-2 的表达与胃癌临床病理特征及预后的关系。方法：选取南昌大学第二附属医院胃肠外科于2009 年1 月至2010 年4 月行手术切除的胃癌组织112 例及与其配对的癌旁组织,采用免疫组织化学法检测肿瘤组织中Flot-2 的表达水平,采用Spearman 检验Flot-2 表达与胃癌临床病理特征及预后的关系,采用Kaplan-Meier 法及Log-Rank 检验分析其生存数据。结果：Flot-2 阳性表达呈黄色颗粒,主要在细胞质中表达,胃癌组织中的表达量明显高于癌旁组织（53.57% vs 46.43%,P<0.05）。Flot-2 表达与患者的性别、年龄、肿瘤位置、分化程度无显著关联（P>0.05）,与肿瘤大小、浸润深度、淋巴结转移、远处转移及AJCC分期均显著关联（均P<0.01）。Flot-2 低表达组患者的5 年总体生存率明显高于高表达组（P<0.01）。Cox 回归分析显示,远处转移、AJCC分期和Flot-2 蛋白表达水平为胃癌患者预后的独立危险因素。结论：胃癌组织中高表达Flot-2,其与患者不良预后密切相关,是胃癌预后的独立危险因素,有望成为胃癌治疗的潜在新靶点。     

新疆地区不同民族胃癌患者HER2蛋白表达与临床病理学特征的关系

目的：利用新疆地区有利条件探究胃癌患者HER2/neu表达与民族及临床病理特征的关系。方法：随机选取2010年-2012年新疆维吾尔自治区人民医院收治的120例原发胃癌患者（胃食管交界处肿瘤33例,胃体部肿瘤35例,胃窦部肿瘤52例）,应用免疫组织化学（ immunohistochemistry,IHC）法检测胃癌患者的HER2/neu表达情况,应用新版《胃癌HER2检测指南》评分标准进行评分。数据分析采用SPSS 17.0统计软件。结果：120例胃癌组织中20例（16.7％）HER2/neu（﹢﹢﹢）,胃食管交界处肿瘤阳性率明显高于胃体/胃窦肿瘤（33.3％ vs 10.3％,P＝0.005）。肠型胃癌阳性率显著高于弥漫性/混合型胃癌（26.7％ vs 6.7％,P＝0.001）。汉族与少数民族（维族、哈族）之间HER2/neu蛋白阳性率（15.7％ vs 17.4％,P＝0.407）无明显差异。结论：肠型胃癌与胃食管交界处肿瘤是曲妥珠单抗联合化疗的主要适宜人群。     

Clinicopathological factors associated with HER2 status in gastric cancer: results from a prospective multicenter observational cohort study in a Japanese population (JFMC44-1101)

Background

Human epidermal growth factor (HER) 2 positivity and its association with clinicopathological factors remain unclear in Japanese gastric cancer (GC) patients. We performed a prospective, multicenter, observational cohort study to evaluate HER2 protein expression and gene amplification in Japanese metastatic and recurrent GC patients, and explored its correlations with clinicopathological features.

Methods

HER2 protein expression and gene amplification were centrally assessed in formalin-fixed, paraffin-embedded GC tissue by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Patient information was collected, and associations between clinicopathological factors and HER2 positivity (IHC score 3+ and/or FISH positive) and low HER2 expression (IHC score 0/FISH positive or IHC score 1+/FISH positive) were examined.

Results

From September 2011 to June 2012, 1461 patients were registered across 157 sites, and the HER2 status of 1427 patients was evaluated. The rate of HER2 positivity was 21.2 %, whereas the rate of high HER2 expression (IHC score 2+/FISH positive or IHC score 3+) was 15.6 % and that of low HER2 expression was 7.0 %. Multiple logistic regression analysis identified intestinal type, absence of peritoneal metastasis, and hepatic metastasis as significant independent factors related to HER2 positivity. The intestinal type was confirmed to be the GC subtype predominantly associated with lower HER2 expression. Sampling conditions including number of biopsy samples, formalin concentration, and formalin-fixation time did not significantly affect HER2 positivity.

Conclusions

HER2 expression in Japanese patients was comparable to that in other populations examined. Intestinal type was an independent factor related to HER2 positivity and low HER2 expression.

     

Type 2 diabetes mellitus and prognosis in early stage breast cancer women

It has been suggested that type 2 diabetes mellitus may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The aim of this study was to determine the impact of diabetes on disease-free survival (DFS) following mastectomy for breast cancer patients. The cases included in this retrospective study were selected from breast cancer women who had undergone mastectomy and completed adjuvant chemotherapy from 1998 to 2010. Patients were classified into two groups: diabetic and non-diabetic. Patients' age, sex, menopausal status, body mass index (BMI), histopathological features, tumor size, lymph node involvement, hormone receptor and HER2-neu status, and treatment types were recorded. There were 483 breast cancer patients included in the study. Postmenopausal patients' rate (53.7% vs. 36.8%, P = 0.016) and mean BMI levels were statistically higher (32.2 vs. 27.9, P = 0.007) in diabetic patients. There was no statistical difference for histological subgroup, grade, ER and PR positivity, HER2-neu overexpression rate, and tumor size between the diabetic and non-diabetic group. Lymph node involvements were statistically higher in diabetic patients compared with non-diabetic patients (P = 0.013). Median disease-free survival is 81 months (95% CI, 61.6-100.4) in non-diabetic patients and 36 months (95% CI, 13.6-58.4) in diabetic patients (P < 0.001). The odds ratio of recurrence was significantly increased in those with HER2-neu overexpression and lymph node involvement and decreased with PR-positive tumors. Our results suggest that diabetes is an independent prognostic factor for breast cancer.     

Simultaneous detection of expression and gene mutations of HER2/neu in Chinese patients with gastric cancer

HER2/neu is one of the few identified oncogenes in tumorigenesis. Attention has been focused on the potential effect of HER2/neu mutations in the tyrosine kinase domain on carcinoma-targeted therapy. However, data concerning HER2/neu mutations in Chinese patients with gastric cancer (GC) are limited. This study aimed to detect the expression and somatic mutations of HER2/neu in Chinese patients with GC. Immunohistochemical staining for HER2/neu was performed on 72 formalin-fixed, paraffin-embedded specimens of GC (40 intestinal and 32 diffuse type). The correlation between the overexpression of HER2/neu and clinicopathological parameters was statistically analyzed. Somatic mutations in the tyrosine kinase domain of HER2/neu in the 72 patients were detected by direct sequencing. In the GC group, overexpression of HER2/neu was detected in 13 of the 72 GC patients and in 4 of the 72 adjacent tissues in the non-tumorous group (18.1 vs. 5.6%, P<0.05). Furthermore, the intestinal type of GC exhibited a higher rate of HER2/neu overexpression than the diffuse type (29.7 vs. 5.7%, P<0.05). The rate of HER2/neu overexpression in stage III-IV (TNM stage) GC cases was significantly higher than that in stage I-II (28.2 vs. 6.6%, P<0.05). HER2/neu overexpression correlated with a significantly less favorable patient survival (P=0.046). No somatic mutations in the tyrosine kinase domain of HER2/neu were detected in tumor tissues or the corresponding non-tumorous ones in the specimens obtained from the 72 Chinese GC patients. Results suggest that overexpression of HER2/neu is a frequent molecular event strongly associated with a poor patient prognosis, whereas the incidence of somatic mutations of the HER2/neu kinase domain is more likely a low-frequency event in Chinese GC patients.     

Factors Associated with HER2 Overexpression in Breast Cancer : Experience in an Asian Developing County

Introduction: The HER2 gene is amplified in up to 30% of human breast cancers, leading to overexpressionof the HER2 protein on the cell surface. Overexpression of HER2 is associated with a more aggressive cancerand hence a poorer overall survival. Objective: To evaluate the association between clinico-pathological featuresand HER2 overexpression in breast cancer. Methods: This is a retrospective study conducted in the Departmentof Surgery, University Malaya Medical Centre. The association between HER2 overexpression, determined byimmunohistochemistry, and other clinicopathological factors was evaluated in 996 patients with newly diagnosedbreast cancer treated from 2005 to 2007 using univariate and multivariate logistic regression. Results: HER2overexpression occurred in 30.3% of patients. On bivariate analysis, HER2 overexpression was inversely relatedto ER expression (p<0.01) and PR expression (p<0.01). This overexpression was associated with a higher tumourgrade, lymphovascular positivity and infiltrating ductal carcinoma subtype. On multivariate analysis, HER2overexpression was significantly associated with higher tumour grade (p=0.018, CI 1.25-11.04), PR negativity(p=0.002, CI 0.30-0.77) and lymphovascular positivity (p=0.042, CI 1.01-2.12). Conclusions: HER2 overexpressionwas observed in 30.3% of Malaysian female breast cancer patients. This group of patients represents a moreaggressive subtype of breast cancer with higher tumour grade, PR negativity and lymphovascular positivity. Nosignificant relationship was established between HER2 overexpression and age, race, lymph node, ER, pathologysubtype and stage of disease from this study.     

Porphyrin modified trastuzumab improves efficacy of HER2 targeted photodynamic therapy of gastric cancer

Gastric cancer (GC) is the 3rd deadliest cancer worldwide, due to limited treatment options and late diagnosis. Human epidermal growth factor receptor‐2 (HER2) is overexpressed in ～20% of GC cases and anti‐HER2 antibody trastuzumab in combination with conventional chemotherapy, is recognized as standard therapy for HER2‐positive metastatic GC. This strategy improves GC patients' survival by 2–3 months, however its optimal results in breast cancer indicate that GC survival may be improved. A new photoimmunoconjugate was developed by conjugating a porphyrin with trastuzumab (Trast:Porph) for targeted photodynamic therapy in HER2‐positive GC. Using mass spectrometry analysis, the lysine residues in the trastuzumab structure most prone for porphyrin conjugation were mapped. The in vitro data demonstrates that Trast:Porph specifically binds to HER2‐positive cells, accumulates intracellularly, co‐localizes with lysosomal marker LAMP1, and induces massive HER2‐positive cell death upon cellular irradiation. The high selectivity and cytotoxicity of Trast:Porph based photoimmunotherapy is confirmed in vivo in comparison with trastuzumab alone, using nude mice xenografted with a HER2‐positive GC cell line. In the setting of human disease, these data suggest that repetitive cycles of Trast:Porph photoimmunotherapy may be used as an improved treatment strategy in HER2‐positive GC patients.     

HER2-neu表达与胃癌预后关系的Meta分析

目的探讨肿瘤组织中HER2-neu表达与胃癌预后的相关性。方法计算机检索相关文献,运用Meta分析方法对纳入文献进行综合定量分析。计算合并相对危险比（HR）和95%可信区间（95% CI）。结果入选文献20篇,包括患者总数为4 398例。有单因素分析结果的文献16篇,一致性检验Q值为27.48（P=0.025）,合并HR为1.57（95%CI 1.30～1.90）;合并多因素分析结果的文献5篇,一致性检验Q值为4.03（P=0.401）,合并HR为1.30（95%CI 1.09～1.52）。结论HER2-neu是胃癌预后不良的一个生物标志物。     

The trichotomy of HER2 expression confers new insights into the understanding and managing for breast cancer stratified by HER2 status

Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that plays a carcinogenic role in breast cancer (BC) through gene amplification, mutation, or overexpression. Traditional methods of HER2 detection were divided into positive (immunohistochemistry (IHC) 3+/fluorescence in situ hybridization (FISH) amplification) and negative (IHC 2+/FISH−, IHC 1+, IHC 0) according to the dichotomy method. Anti-HER2-targeted therapies, such as trastuzumab and pertuzumab, have significantly improved the prognosis of HER2-positive patients. However, up to 75% to 85% of patients remain HER2-negative. In recent years, with the rapid development of molecular biology, gene detection technology, targeted therapy, and immunotherapy, researchers have actively explored the clinicopathological characteristics, molecular biological characteristics, treatment methods, and HER2 detection methods of HER2-low/zero breast cancer. With the clinical efficacy of new anti-HER2 targeted drugs, accurate classification of breast cancer is very important for the treatment choice. Therefore, the following review summarizes the necessity of developing HER2 detection methods, and the clinicopathological and drug treatment characteristics of patients with HER2-low/zero, to light the dawn of the treatment of breast cancer patients with HER2-low/zero expression.