Pathologic Diagnostics of HER2 Positivity in Gastroesophageal Adenocarcinoma

Koopman, Timco; Louwen, Maarten; Hage, Maria Cristina Ferrarini Nunes Soares; Smits, Maria M.; Imholz, Alex L.T.

doi:10.1309/ajcpcx69hgddgycq

Cited by 19 publications

(21 citation statements)

References 29 publications

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“…Anti-HER2 therapy is an established part of breast-and gastroesophageal cancer treatment. [14][15][16][17][18][19][20][21][22] Trastuzumab was shown to reduce ovarian CCC cell lines in vitro, 36 but no clinical data of anti-HER2 therapy in endometrial or ovarian CCC are available. In other endometrial carcinoma subtypes, clinical activity of trastuzumab has been described in several case reports.…”

Section: Discussionmentioning

confidence: 99%

“…A possible target for therapy is the human epidermal growth factor receptor 2 (HER2/ErbB2), well known from its clinical significance in HER2-positive breastand gastroesophageal cancer. [14][15][16][17][18][19][20][21][22] In endometrial and ovarian cancer, HER2-positivity varies considerably: 17-80% in endometrial and 8-66% in ovarian carcinoma. [23][24][25] Specific data on CCC are scarce, with 14-67% HER2-positivity reported in small patient cohorts (often n < 10).…”

Section: Introductionmentioning

confidence: 99%

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HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in‐situ hybridisation

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in‐situ hybridisation

et al. 2018

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“…Trastuzumab provides modest overall survival benefit for patients with HER2-positive advanced GEA in the firstline setting in combination with active cytotoxics. 48 The ToGA trial 3 used the HercepTest antibody, and many studies 30, [49][50][51][52][53] have used 4B5 or CB11. There is generally moderate to good concordance between various antibodies, [54][55][56][57][58] although several articles note stronger staining for 4B5 than for other antibodies.…”

Section: Strong Recommendationmentioning

confidence: 99%

HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology

Bartley

Washington

Colasacco

et al. 2017

JCO

317

275

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Context ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. Objectives To establish an evidence-based guideline for HER2 testing in patients with GEA, formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making. Design The College of American Pathologists (CAP), American Society for Clinical Pathology (ASCP), and the American Society of Clinical Oncology (ASCO) convened an Expert Panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA. Results The Panel is proposing 11 recommendations with strong agreement from the open comment participants. Recommendations The Panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and an HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance. Conclusion This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results.

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“…To date, a number of studies have tested the diagnostic value of IHC in detecting HER-2 positivity in gastric cancer in reference to more sophisticated molecular methods [7,9,[16][17][18][19][20][21][22][23]. Most comprehensive data on the concordance between IHC and SISH methods comes from a recent meta-analysis, which included a total of 12,679 cases from 45 individual studies [7].…”

Section: Discussionmentioning

confidence: 99%

Human epidermal growth factor receptor 2 (HER-2) status evaluation in advanced gastric cancer using immunohistochemistry versus silver in situ hybridization

Kepil

Batur

Wetherilt

et al. 2016

Bosn J of Basic Med Sci

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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 diagnosed with locally advanced (Stage III: T3-4, N+) recurrent or metastatic adenocarcinoma of the stomach or esophagogastric junction, between 2009 and 2015, were included. HER-2 status was examined using both IHC and SISH techniques and the findings were compared. Overall SISH-confirmed HER-2 positivity rate was 22%. Multivariate analysis identified only well-differentiated tumor as a significant predictor of HER-2 positivity (OR: 2.9, 95% CI: 1.4-5.9, p = 0.003). When IHC 2+ and 3+ were considered positive for HER-2 status, sensitivity, specificity, and concordance rate (κ) was 95.7%, 93.8%, and 0.84, respectively. Corresponding figures when only IHC 3+ cases were considered positive were lower: 50%, 100%, and 0.61, respectively. The present method used for the identification of HER-2 positive gastric cancer patients provides satisfactory results. However, better categorization of IHC 2+ cases has the potential to improve the diagnostic accuracy, which is particularly important when more sophisticated methods are not readily available.

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Pathologic Diagnostics of HER2 Positivity in Gastroesophageal Adenocarcinoma

Abstract: The currently used standardized HER2 scoring system is an excellent, clinically applicable method to establish HER2 status in appropriately educated and trained pathologists.

Cited by 19 publications

References 29 publications

HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in‐situ hybridisation

HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in‐situ hybridisation

HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology

Human epidermal growth factor receptor 2 (HER-2) status evaluation in advanced gastric cancer using immunohistochemistry versus silver in situ hybridization

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