Impact of Specimen Type and Specimen Number on HER2 Status in Gastroesophageal Junction and Gastric Adenocarcinoma

Huber, Aaron R; Buscaglia, Brandon; Koltz, Brooke; Henry, Jill E.; McMahon, Loralee; Guo, James; Whitney-Miller, Christa L.

doi:10.1093/ajcp/aqy166

Cited by 9 publications

(9 citation statements)

References 32 publications

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“…43 Repeat HER2 testing has also been shown to increase the rate of HER2 positivity in gastric cancer. 44 Current Criteria (Approved or Proposed) for HER2 Positivity by Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) in Different Tumor Types Breast (ASCO/CAP 2018) 23 Gastric (ASCO/CAP 2016) 36 Colorectal (HERACLES Trial) 39 Endometrial Serous (Fader et Huber et al 44 assessed the impact of specimen type on HER2 status in gastric and gastroesophageal junction adenocarcinomas, and they reported that in patients with only 1 specimen 10.5% of tumors were HER2 þ , whereas the rate increased to 18.1% and 24.1% in patients with 2 or 3 specimens tested, respectively. Discordant HER2 status has also been observed between paired primary and metastatic tumors in close to 20% of breast, gastric, and most recently endometrial carcinomas.…”

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confidence: 99%

“…Discordant HER2 status has also been observed between paired primary and metastatic tumors in close to 20% of breast, gastric, and most recently endometrial carcinomas. [44][45][46] Furthermore, the optimal HER2 testing algorithm also depends on the correlation between the test type (IHC or FISH) and therapeutic response, although specific data for endometrial carcinoma are currently limited in the literature. In breast cancer, FISH and IHC are equally predictive of clinical response; hence, the current ASCO/CAP guidelines allow for either test to be performed primarily and recommend reflexing to the other method in cases with an equivocal result.…”

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HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand

Buza

2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Endometrial serous carcinoma is an aggressive subtype of endometrial cancer with the highest rate of recurrence and mortality among all histotypes. A recent clinical trial showed prolonged progression-free survival in advanced-stage and recurrent human epidermal growth factor receptor 2 (HER2)–positive endometrial serous carcinoma when trastuzumab was added to the standard chemotherapy regimen. This targeted therapeutic approach was recently endorsed by the National Comprehensive Cancer Network clinical guidelines. There is a growing interest among clinicians to obtain HER2 testing in endometrial serous carcinoma, and pathologists need to be prepared to recognize the unique characteristics of HER2 protein expression and gene amplification in these tumors and apply specific HER2 scoring criteria. Objective.— To provide a historical overview of targeted HER2 therapy in endometrial serous carcinoma and to summarize key findings from recent studies on the specific features of HER2 protein expression and gene amplification relative to other tumor types. Endometrial carcinoma–specific HER2 testing criteria are proposed based on evidence in the existing literature. Data Sources.— Sources comprise review of the literature and personal experience of the author. Conclusions.— HER2 protein overexpression and/or gene amplification is present in approximately 25% to 30% of endometrial serous carcinomas, providing an opportunity for targeted therapy. Pathologists play a key role in tumor HER2 testing and scoring to ensure appropriate patient selection and successful clinical outcome.

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confidence: 99%

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HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand

Buza

2020

Archives of Pathology &Amp; Laboratory Medicine

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“…Discordant HER2 status between primary and metastatic tumours has been demonstrated in breast, gastric and endometrial cancers. [31][32][33] The most common scenario is HER2-positive primary tumours with discordant HER2-negative metastases, and a reverse pattern can rarely occur. The major cause of such discordance is intratumoral heterogeneity, which is considerably higher in gastric cancer and endometrial serous carcinoma than in breast cancer.…”

Section: Discussionmentioning

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Analytical validation of human epidermal growth factor receptor 2 immunohistochemistry by the use of the A0485 antibody versus the 4B5 antibody and breast versus gastric scoring guidelines in ovarian clear cell carcinoma

et al. 2021

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AimsThe aim of this study was to evaluate human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) in ovarian clear cell carcinoma (OCCC) by using two antibodies and two scoring guidelines in correlation with HER2 amplification and clinicopathological features.Methods and resultsA tissue microarray was constructed by use of a total of 71 OCCC cases for IHC (the A0485 antibody and the 4B5 antibody) and dual‐colour silver in‐situ hybridisation (DISH). Two pathologists independently scored the IHC according to the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) breast cancer guidelines (breast guidelines) and the 2016 ASCO/CAP gastro‐oesophageal adenocarcinoma guidelines (gastric guidelines). IHC concordances between A0485 and 4B5 were 87.3–93.0%. Three to 16 (4.2–22.5%) cases had an IHC score of 2+/3+ with frequent basolateral/lateral membranous staining. The 4B5 antibody yielded fewer IHC 2+ cases than the A0485 antibody (n = 2–6 versus n = 5–12). Five (7.0%) cases had HER2 amplification as determined with DISH. Cases with papillary‐predominant growth patterns were significantly more likely to have HER2 amplification (P = 0.0051). In predicting DISH results, IHC scored according to the gastric guidelines yielded 100%/100% sensitivity and 83.3–95.5%/98.2–100% specificity, and IHC scored according to the breast guidelines yielded 60–80%/33.3–66.7% sensitivity and 95.5–100%/100% specificity (including/excluding IHC 2+ cases). One case had intratumoral heterogeneity, with discordant results between primary and metastatic tumour specimens.ConclusionWe demonstrated HER2 amplification in 7% of OCCC cases, and the molecular change is significantly associated with papillary‐predominant growth patterns. In predicting HER2 amplification, a combination of 4B5 IHC and gastric guidelines provides the best sensitivity and fewer equivocal (IHC 2+) cases. Given the intratumoral heterogeneity, assessment of HER2 status on whole tissue sections and on both primary and metastatic tumour specimens is recommended.

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“…According to current literature, the frequency of HER2 overexpression/amplification in EA and GC tends to be different, ranging from 7% to 42% [64][65][66][67]. A slight greater HER2 positivity incidence has been reported in EA (24%-35%), more frequently in the subgroup of intestinal-type, in comparison to GC (9.5%-21%) [68][69][70].…”

Section: Her2 In Gastro-oesophageal Malignant Lesionsmentioning

confidence: 98%

“…About HER2 protein regulation, specific miRNAs, such as miR-125a-5p, miR-125b, miR-205, miR-331-3p and miR-146a have been proposed to straightly affect HER2 expression [61][62][63][64]. In addition, HER2 transcript suppression may represent the result of miR-125a-5p and/or miR-125b expressed in HER2-positive breast cancer cell lines infected with retroviral constructs [61][62][63].…”

Section: High-grade Dysplasia (Hgd)mentioning

confidence: 99%

HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies

Ieni

Cardia

Pizzimenti

et al. 2020

JPM

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Human epidermal growth factor receptor-2 (HER2)-expression gastro-oesophageal adenocarcinomas (GEA) gained interest as an important target for therapy with trastuzumab. In the current review, we focused the current knowledge on HER2 status in dysplastic and neoplastic gastric conditions, analyzing the methodological procedures to identify HER2 expression/amplification, as well as the proposed scoring recommendations. One of the most relevant questions to evaluate the useful impact of HER2 status on therapeutic choice in GEAs is represented by the significant heterogeneity of HER2 protein and gene expression that may affect the targeted treatment selection. Future development of biotechnology will continue to evolve in order to offer more powerful detection systems for the assessment of HER2 status. Finally, liquid biopsy as well as mutation/amplification of several additional genes may furnish an early detection of secondary HER2 resistance mechanisms in GEAs with a better monitoring of the treatment response.

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Impact of Specimen Type and Specimen Number on HER2 Status in Gastroesophageal Junction and Gastric Adenocarcinoma

Cited by 9 publications

References 32 publications

HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand

HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand

Analytical validation of human epidermal growth factor receptor 2 immunohistochemistry by the use of the A0485 antibody versus the 4B5 antibody and breast versus gastric scoring guidelines in ovarian clear cell carcinoma

HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies

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