HER2 expression status in diverse cancers: review of results from 37,992 patients

Yan, Min; Schwaederlé, Maria; Arguello, David; Millis, Sherri Z.; Gatalica, Zoran; Kurzrock, Razelle

doi:10.1007/s10555-015-9552-6

Cited by 371 publications

(291 citation statements)

References 47 publications

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“…Elevated CEP17 count (polysomy) has been linked with adverse clinicopathologic features and HER2 overexpression, although there are numerous discrepancies in the literature (37). HER2 overexpression and/or amplification are recurrently reported in numerous tumor types, and have been shown to have significant therapeutic implications in patients with cancer (33). A meta-analysis of 5,976 patients demonstrated that HER2/neu overexpression was associated with mortality and recurrence in patients with PCa (52).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have used immunohistochemical analysis to evaluate HER2 protein expression in primary prostate specimens, demonstrating expression rates ranging from 0-100% (29)(30)(31). Therefore, the exact prevalence of HER2 gene amplifications in primary PCa remains unknown, likely owing to the wide range of antibodies and methods used in these studies (32,33).…”

Section: Her2 Gene Amplification In Patients With Prostate Cancermentioning

confidence: 99%

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HER2 gene amplification in patients with prostate cancer: Evaluating a CISH-based method

et al. 2016

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Abstract. Prostate cancer (PCa) is one of the most widespread malignancies in the world. The role of the human epidermal growth factor receptor 2 (HER2) in the pathogenesis and progression of human PCa remains poorly understood. In contradiction with breast cancer, studies on HER2 overexpression and gene amplification in PCa have produced varying results, although the HER2 oncogene has been implicated in the biology of numerous tumor types, and serves as a prognostic marker and therapeutic target in breast cancer. Technical challenges are considered the main reasons for data discrepancies. Amplification of the HER2 gene has previously been reported in PCa, in which it was associated with tumor progression. The present study aimed to evaluate the prevalence and clinical significance of HER2 amplification in PCa. A total of 32 biopsy samples obtained from human prostate adenocarcinomas were evaluated by chromogenic in situ hybridization (CISH) to determine the frequency of patients with HER2 gene amplifications. High copy numbers of HER2 were detected in 19 of the prostate tumors analyzed. The results of the present study suggested that, in patients without amplification of HER2, high levels of prostate-specific antigen or a high Gleason score were not significantly correlated with a high pathologic stage. Furthermore, amplification levels of the HER2 gene were directly associated with pathologic stage in patients with PCa. Therefore, the potential use of HER2 as a prognostic factor or therapeutic target for PCa warrants further study. IntroductionProstate cancer (PCa), a common non-skin, sex-limited cancer, is the second cause of cancer-associated mortality (after lung cancer) in the USA (1,2) and the second most prevalent cancer among Iranian men (3). Worldwide, PCa is the second most commonly diagnosed cancer and, according to the International Agency for Research on Cancer's GLOBOCAN 2012 (4) database, it is the fifth leading cause of cancer-associated mortality in men. The incidence of PCa is increasing worldwide, although there is a marked variation in its incidence among different regions (5). The clinical configuration of PCa has noticeably altered over the past few years. As a localized disease, it is easily treated by radical radiation therapy or a prostatectomy; however, if the tumor becomes malignant, it transforms into a life-threatening disease (6).The progression and application of novel high-resolution technologies has enhanced the detection of genomic alterations, enabling elucidation of the complex nature and heterogeneity of PCa (7). The differentiation of PCa tumors is typically based on the serum expression levels of prostate-specific antigen (PSA), although, in certain cases, PSA levels do not accurately reflect tumor burden (8). Previous studies have identified a number of genetic, epigenetic and environmental risk factors for PCa (9-11). Among them, genetic aberrations and chromosomal changes have been suggested to serve a significant role in the development and progression of PCa (12)

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Section: Discussionmentioning

confidence: 99%

Section: Her2 Gene Amplification In Patients With Prostate Cancermentioning

confidence: 99%

HER2 gene amplification in patients with prostate cancer: Evaluating a CISH-based method

et al. 2016

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“…A recent study has evaluated gene amplification and expression status by FISH and IHC in a large cohort of more than 37,000 tumors, in which UC was the most frequently HER2 expressing tumor type of all tested solid tumors [4]. Among 475 examined UC samples, 12.4% strongly expressed HER2 (IHC 3+) and IHC correlated in >90% with positive FISH.…”

Section: Discussionmentioning

confidence: 99%

Complete and Durable Remission of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Urothelial Carcinoma Following Third-Line Treatment with Trastuzumab and Gemcitabine

Wezel

Erben²,

Gaiser³

et al. 2016

Urol Int

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Urothelial carcinoma (UC) is one of the most common cancers and survival rates are low in metastatic disease with currently established first-line platinum-based chemotherapies. Unlike in many other cancers, no clinically established molecular targeted therapies exist for the treatment of this malignancy. Here we present a case of complete tumor remission following third-line treatment with trastuzumab and gemcitabine in a patient with human epidermal growth factor receptor 2 (HER2)-positive UC after progression under cisplatin and vinflunine chemotherapies. This case shows the potential significance of anti-HER2 therapy in selected patients with molecularly characterized UC. Clinical trials so far show inconclusive outcomes of anti-HER2 therapies in UC, indicating further need for both basic research and clinical studies for the identification of resistance factors and improved patient selection.

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“…Among the array of responsible genes, one of the most flagrant genetic aberrations was ascribed to HER-2 in GBC [10]. Yan et al [12] reported that HER-2 overexpression was detected predominantly in malignancies of epithelial origin. Furthermore, the availability of FDA-approved agents targeting HER-2-positive malignancies, such as trastuzumab and pertuzumab (humanized monoclonal antibodies) and lapatinib and afatinib (dual EGFR/HER2 inhibitors), makes it a marker of choice for testing in GBC.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of HER-2 and p53 Expression in Gallbladder Carcinoma in North Indian Patients

et al. 2016

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Background/Objective: Proto-oncogenes (HER-2) and tumor suppressor genes (p53) are commonly deregulated in gallbladder cancer (GBC). Available literature discloses skewed data from endemic Asian countries, especially north India. This study evaluates the prognostic significance of HER-2 and p53 in GBC patients from two major hospitals. Methods: Sixty resectable tumor and control specimens were prospectively collected from December 2012 to January 2016. Immunohistochemical staining was done using monoclonal antibodies to semiquantitatively evaluate HER-2 and p53 protein expression. The criterion for HER-2 positivity was set at >30% tumor cells showing complete, membranous staining while p53 positivity was established at <50% tumor cells showing complete nuclear staining. Clinicopathological correlations were drawn with major clinical outcomes. Results: It was observed that 36.67% (22/60) tumor cases and 5% (3/60) control cases showed strong HER-2 overexpression significantly correlating with sex, T-stage, nodal spread and distant metastasis (p < 0.05), while 33.3% (20/60) positivity was observed for p53 in tumor cases and 1.7% (1/60) in control cases. Multivariate analysis showed HER-2 (p = 0.04; hazard ratio: 2.36; 95% confidence interval: 1.04-5.33) and p53 (p = 0.03; hazard ratio: 5.63; 95% confidence interval: 1.21-26.26) expression to be independent prognostic factors. Conclusion: Our study thus suggests the plausible role of HER-2 and p53 expression in worse prognosis of GBC in a north Indian population.

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HER2 expression status in diverse cancers: review of results from 37,992 patients

Cited by 371 publications

References 47 publications

HER2 gene amplification in patients with prostate cancer: Evaluating a CISH-based method

HER2 gene amplification in patients with prostate cancer: Evaluating a CISH-based method

Complete and Durable Remission of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Urothelial Carcinoma Following Third-Line Treatment with Trastuzumab and Gemcitabine

Prognostic Significance of HER-2 and p53 Expression in Gallbladder Carcinoma in North Indian Patients

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