scholarly journals Somatic mutation profiling and HER2 status in KRAS-positive Chinese colorectal cancer patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhouhuan Dong ◽  
Linghong Kong ◽  
Zhiyi Wan ◽  
Fengwei Zhu ◽  
Mei Zhong ◽  
...  
Keyword(s):  
Predictive Value ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Her2 Status ◽  
Molecular Features ◽  
Epidermal Growth ◽  
Colorectal Cancer Patients ◽  
Next Generation Sequencing Ngs ◽  
Mutation Profiling

AbstractKRAS is an independent negative predictor for anti-epidermal growth factor receptor (anti-EGFR) treatment in colorectal cancers (CRCs). However, 30% to 50% of CRC patients are KRAS-positive and do not benefit from anti-EGFR therapy. In this study, we investigated the mutational features and clinical significance of KRAS-positive Chinese CRC patients. A total of 139 Chinese CRC patients who received clinical KRAS testing (Sanger sequencing) were examined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Fifty KRAS-positive specimens were further detected by next-generation sequencing (NGS). The most prevalent mutation in KRAS was G12D (46%), followed by G12V (20%), and G13D (18%). In addition to KRAS, 72 unique alterations in another 12 genes were also detected. The most common mutated genes were TP53 (62%), APC (46%), and PIK3CA (22%). The proportion of HER2 amplifications in KRAS-positive CRC patients was 4.4%, which was lower than that in KRAS -negative CRC patients (14.3%). No relationship was found between HER2 amplification and KRAS status (p = 0.052). However, the odds ratio is very low (0.279). In addition, these gene mutations were not significantly associated with age, sex, tumor size, lymph node metastasis, mismatch repair–deficient, or tumor differentiation. However, TP53 mutations were more prevalent in colon cancer with KRAS mutations than in rectal cancer (75.0% vs 28.6%, respectively, p = 0.004). The negative predictive value of the IHC analysis for predicting HER2 amplification reached to 98.39%, while the positive predictive value reached only 50%. Overall, the mutation profiling of Chinese CRC patients with KRAS mutations is different from that of Western CRC patients. Our results will help us to understand the molecular features of Chinese CRC patients.

Human Epidermal Growth Factor Receptor 2 Assessment in a Case-Control Study: Comparison of Fluorescence In Situ Hybridization and Quantitative Reverse Transcription Polymerase Chain Reaction Performed by Central Laboratories

2010 ◽  
Vol 28 (28) ◽  
pp. 4300-4306 ◽  
Author(s):  
Frederick L. Baehner ◽  
Ninah Achacoso ◽  
Tara Maddala ◽  
Steve Shak ◽  
Charles P. Quesenberry ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Oncotype Dx ◽  
Her2 Status ◽  
Rt Pcr ◽  
Her2 Positive ◽  
Polysomy 17 ◽  
Epidermal Growth ◽  
Polymerase Chain ◽  
Control Study

Purpose The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate ≥ 95% concordance to another approved laboratory or methodology. Here, we compare central laboratory HER2 assessed by fluorescence in situ hybridization (FISH) and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using Oncotype DX in lymph node–negative, chemotherapy-untreated patients from a large Kaiser Permanente case-control study. Patients and Methods Breast cancer specimens from the Kaiser–Genomic Health study were examined. Central FISH assessment of HER2 amplification and polysomy 17 was conducted by PhenoPath Laboratories (ratios > 2.2, 1.8 to 2.2, and < 1.8 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). HER2 expression by RT-PCR was conducted using Oncotype DX by Genomic Health (normalized expression units ≥ 11.5, 10.7 to < 11.5, and < 10.7 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). Concordance analyses followed ASCO/CAP guidelines. Results HER2 concordance by central FISH and central RT-PCR was 97% (95% CI, 96% to 99%). Twelve percent (67 of 568 patients) and 11% (60 of 568 patients) of patients were HER2 positive by RT-PCR and FISH, respectively. HER2-positive patients had increased odds of dying from breast cancer compared with HER2-negative patients. Polysomy 17 was demonstrated in 12.5% of all patients and 33% of FISH-positive patients. Nineteen of 20 FISH-positive patients with polysomy 17 were also RT-PCR HER2 positive. Although not statistically significantly different, HER2-positive/polysomy 17 patients tended to have the worst prognosis, followed by HER2-positive/eusomic, HER2-negative/polysomy 17, and HER2-negative/eusomic patients. Conclusion There is a high degree of concordance between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status, and the assay warrants additional study in a trastuzumab-treated population.

scholarly journals Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1503-1512
Author(s):  
Mirjana Miladinović ◽  
Ljiljana Vučković ◽  
Aleksandra Klisic
Keyword(s):  
Lung Adenocarcinoma ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Amplification ◽  
Standardized Protocol ◽  
Molecular Therapies ◽  
Targeted Molecular Therapies ◽  
Epidermal Growth

Abstract Background Discordant results exist about the role of human epidermal growth factor receptor 2 (HER2) overexpression and/or HER2 amplification in lung adenocarcinoma. We aimed to compare the performance of HercepTest and PATHWAY anti-HER2 (4B5) by correlating immunohistochemistry (IHC) results with silver in situ hybridization (SISH) in adenocarcinoma lung specimens. Methods A total of 148 surgically resected adenocarcinoma lung specimens were included. Results HER2 overexpression was found in 7.4% patients for HercepTest Dako and in 2.7% patients for 4B5 antibody. The overall coincidence between these two types of antibodies equals 93.9%. The incidence of HER2 amplification in lung adenocarcinoma was 17.6%, of which in 2.7% of the cases high-grade amplification was present. HER2 amplification was present in 90.9% of patients with overexpression of HER2, obtained by using HercepTest Dako and 75% patients using 4B5 antibody. A significant correlation between overexpression of HER2 receptors obtained by HercepTest Dako and 4B5 antibody and HER2 amplification was shown. Conclusion The research of the efficiency of targeted molecular therapies with an HER2 antibody may serve as a basis for the introduction of routine HER2 status determination in lung adenocarcinoma, dictating the need for the standardized protocol for HER2 status determination in such pathology.

scholarly journals Utility of Alternate, Noncentromeric Chromosome 17 Reference Probe for Human Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization Testing in Breast Cancer Cases

2018 ◽  
Vol 142 (5) ◽  
pp. 626-633 ◽  
Author(s):  
Trupti Pai ◽  
Tanuja Shet ◽  
Asawari Patil ◽  
Omshree Shetty ◽  
Angad Singh ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Chromosome 17 ◽  
Her2 Status ◽  
Breast Cancers ◽  
Reference Probe ◽  
Epidermal Growth

Context PathVysion—a US Food and Drug Administration–approved dual-probe human epidermal growth factor receptor (HER2) fluorescence in situ hybridization (FISH) assay—provides the HER2:CEP17 ratio, a centromeric enumeration probe ratio for determining HER2 status in breast cancers. However, pericentromeric amplifications might then skew the HER2:CEP17 ratio, underestimating the HER2 status, which calls into question the use of CEP17 as the reference probe. Objective To analyze the utility of a noncentromeric chromosome 17 reference locus (D17S122) to assess HER2 gene status in cases showing “nonclassical” FISH patterns with the CEP17 probe. Design The HER2 status of breast cancers accessioned in the years 2015–2017, displaying “nonclassical” or “equivocal” results by the PathVysion (Abbott Molecular Inc, Des Plaines, Illinois) HER2 DNA Probe Kit were reflex tested using an alternate FISH probe (ZytoLight SPEC/D17S122, ZytoVision, Bremerhaven, Germany) and interpreted with American Society of Clinical Oncology/College of American Pathologists 2013 guidelines. Results Of 37 cases, 17 were FISH equivocal. With the alternate D17S122 probe, 13 (76.4%) were reclassified as amplified, 3 (17.6%) as nonamplified, and a single case retained an equivocal result. Of the 17 cases with a chromosome 17 polysomy pattern, disomy, polysomy, and monosomy patterns were seen with 14 cases, 2 cases, and 1 case, respectively. Within the 17 cases with polysomy pattern, 3 (17.6%) demonstrated an unusual colocalization pattern of HER2 and CEP17, which was not observed with the alternate probe. Conclusions The denominator-stable alternate probe is a useful adjunct in the diagnostic armamentarium to analyze HER2 status in cases with FISH equivocal and complex patterns.

scholarly journals Quantitative Impact of the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Practice Guideline Update on Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Breast Cancer: A Systematic Analysis

2020 ◽  
Author(s):  
Christina H. Wei ◽  
Lino Garcia ◽  
Joyce Murata-Collins ◽  
Daniel Schmolze ◽  
Sophia Apple
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Fluorescence In Situ Hybridization ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Epidermal Growth ◽  
American Society ◽  
Quantitative Impact

Context.— The global impact of the new 2018 American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) practice guideline update on the overall HER2 status designation, compared with the prior 2013 iteration, is unknown. Objectives.— To report the quantitative impact of the new guideline on HER2 status distribution. Design.— The analysis comprised a retrospective cohort of patients from the author's institution, combined with other peer-reviewed publications that assessed the impact of the 2018 guideline in relation to the 2013 guideline. Results.— Our study revealed that the new guideline led to an average 9% reclassification rate for the overall HER2 status, with a net gain in overall HER2 negative designation. This is largely due to reclassification of the equivocal (Group 4) groups. Unexpectedly, infrequent but consistent discordance between Group 1/5 and fluorescence in situ hybridization results are observed across studies (1.8%; 73 of 3965 cases where fluorescence in situ hybridization and immunohistochemistry are both reported). Conclusions.— Early clinical recognition of these resultant changes, including emerging issues of tumor heterogeneity, and potential discordance between immunohistochemistry to fluorescence in situ hybridization, is important for accurate clinical assessment of individual HER2 test results.

scholarly journals Impact of the 2018 ASCO/CAP HER2 Guideline Focused Update

2019 ◽  
Vol 152 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Adlin M Gordian-Arroyo ◽  
Debra L Zynger ◽  
Gary H Tozbikian
Keyword(s):  
Invasive Carcinoma ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Her2 Positive ◽  
Positive Rate ◽  
Epidermal Growth ◽  
American Society ◽  
The Impact ◽  
Positive Breast Cancer

ABSTRACT Objectives The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) guideline focused update revises the HER2 scoring criteria. We evaluated the impact on HER2 rates in breast carcinoma diagnosed at our center. Methods In a retrospective series of breast core biopsies with invasive carcinoma diagnosed between 2014 and 2017 (n = 1,350), HER2 status was classified according to 2013 and 2018 ASCO/CAP guidelines and changes in HER2 status identified. Results The 2018 guidelines reclassified the HER2 status of 6% of patients. Most changed from HER2 equivocal status (equivocal by immunohistochemistry and fluorescence in situ hybridization under the 2013 guidelines) to HER2-negative status (2018 guidelines). The HER2-positive rate decreased by 0.4%. Conclusions The 2018 guidelines decrease the rate of HER2 equivocal and positive breast cancer and reduce repeat HER2 testing on excision specimens. Approximately 0.4% of patients will become newly ineligible for anti-HER2 therapy.

EGFR Overexpression and Sequence Analysis of KRAS, BRAF, and EGFR Mutation Hot Spots in Canine Intestinal Adenocarcinoma

2021 ◽  
pp. 030098582110097
Author(s):  
Seung-Hee Cho ◽  
Byung-Joon Seung ◽  
Soo-Hyeon Kim ◽  
Min-Kyung Bae ◽  
Ha-Young Lim ◽  
...  
Keyword(s):  
Hot Spots ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Mrna Levels ◽  
Mutation Status ◽  
In Situ Carcinoma ◽  
Egfr Expression ◽  
Rna In Situ Hybridization ◽  
Epidermal Growth

Epidermal growth factor receptor (EGFR) is overexpressed in many human colorectal cancers and anti-EGFR agents are employed as immunotherapies. However, KRAS, EGFR, and BRAF gene mutations can influence the activity of the anti-EGFR agents. We evaluated EGFR expression at protein and mRNA levels in canine intestinal adenocarcinomas using immunohistochemistry (IHC) and RNA in situ hybridization (RNA-ISH). We also investigated the mutation status of EGFR, KRAS, and BRAF to aid the development of anti-EGFR agents for canine intestinal adenocarcinoma. EGFR expression was highest in adenocarcinoma, followed by intramucosal neoplasia (adenoma and in situ carcinoma), and nonneoplastic canine intestinal tissue, at both protein ( P = .000) and mRNA ( P = .005) levels. The EGFR, KRAS, and BRAF genes showed wild-type sequences at the mutation hot spots in all 13 specimens. Thus, EGFR might serve as a promising diagnostic marker in canine intestinal adenocarcinoma, and further studies would be needed to develop EGFR-targeted anticancer therapies.

Not All Cases of Mammary Paget’s Disease are Cytokeratin-7 Positive: A Challenging Diagnosis!

2021 ◽  
pp. 106689692110029
Author(s):  
Kerschen Anja ◽  
Dano Hélène ◽  
Van Eeckhout Pascal ◽  
Marot Liliane ◽  
Van Bockstal Mieke
Keyword(s):  
Present Report ◽  
Paget’S Disease ◽  
Growth Factor Receptor ◽  
Punch Biopsy ◽  
Paget's Disease ◽  
Cytokeratin 7 ◽  
In Situ Carcinoma ◽  
Epidermal Growth ◽  
Mammary Paget’S Disease

Mammary Paget’s disease accounts for 1% to 3% of all breast tumors and manifests as a chronic eczematous lesion of the areolar skin. It can occur without any underlying neoplasia or can be present in association with an underlying invasive and/or in situ carcinoma of the breast. The present report describes a challenging nipple punch biopsy showing an infiltration of the lower third to two-thirds of the epidermis by large, ovoid, neoplastic cells. The morphology was consistent with mammary Paget's disease, although immunohistochemistry for cytokeratin-7 (CK7) was repeatedly negative. This resulted in an initial misdiagnosis and, subsequently, a delay in the patient's follow-up. Additional immunohistochemistry for GATA binding protein 3 (GATA3) and human epidermal growth factor receptor 2 (HER2), as well as a second opinion of a breast pathologist, resulted in the diagnosis of mammary Paget's disease. The aim of this article is to raise awareness among pathologists and prevent them from misdiagnosing CK7-negative Paget disease of the breast.

scholarly journals The Prognostic Impact of HER2 Genetic and Protein Expression in Pancreatic Carcinoma—HER2 Protein and Gene in Pancreatic Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 653
Author(s):  
Song-Hee Han ◽  
Ki Hyun Ryu ◽  
Ah-Young Kwon
Keyword(s):  
Protein Expression ◽  
Genetic Heterogeneity ◽  
Growth Factor Receptor ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Her2 Expression ◽  
Her2 Protein ◽  
Epidermal Growth ◽  
Her2 Heterogeneity

Pancreatic ductal adenocarcinoma (PDAC) is a lethal and clinically heterogeneous disease with a limited benefit from human epidermal growth factor receptor 2 (HER2)-targeted therapy. Recently, some studies have addressed the antitumoral effect of novel anti-HER2 drugs in HER2 low-expressing tumors. However, there have been few studies on the significance of low HER2 expression and genetic heterogeneity in PDAC. Using immunohistochemistry and dual-color silver-enhanced in situ hybridization based on the Trastuzumab for a gastric cancer scoring scheme, we evaluated HER2 protein expression, gene amplification, and genetic heterogeneity in three groups (HER2-neg, HER2-low, HER2-pos) of 55 patients. Among the 55 cases, 41.8% (23/55) showed HER2 expression of any intensity. HER2 amplification independent of HER2 expression was 25.5% (14/55). Patients in both these groups had a shorter overall survival than did patients in the HER2-neg group. HER2 genetic heterogeneity was identified in 37 (70.9%) of the 55 cases, mainly in HER2-neg and HER2-low groups. HER2 genetic heterogeneity significantly correlated with worse survival in the HER2-low and HER2-neg groups of PDAC. These findings support the hypothesis that low-level HER2 expression and heterogeneity have significant clinical implications in PDAC. HER2 heterogeneity might indicate the best strategies of combination therapies to prevent the development of subdominant clones with resistance potential.

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