Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-08-16

AUTHORS

Nicola Personeni, Marina Baretti, Silvia Bozzarelli, Paola Spaggiari, Luca Rubino, Maria Chiara Tronconi, Uberto Fumagalli Romario, Riccardo Rosati, Laura Giordano, Massimo Roncalli, Armando Santoro, Lorenza Rimassa

ABSTRACT

BackgroundHER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma.MethodsHER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri- or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC.ResultsEighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22–0.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13–0.83), P < 0.018], independent of clinical-pathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared.ConclusionsHER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2. More... »

PAGES

428-437

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10120-016-0625-1

DOI

http://dx.doi.org/10.1007/s10120-016-0625-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042491124

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27530622


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31 schema:description BackgroundHER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma.MethodsHER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri- or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC.ResultsEighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22–0.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13–0.83), P < 0.018], independent of clinical-pathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared.ConclusionsHER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2.
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38 schema:keywords BackgroundHER2
39 ConclusionsHER2 status
40 HER2
41 HER2 analysis
42 HER2 assessment
43 HER2 expression
44 HER2 positivity
45 HER2 protein expression
46 HER2 status
47 IHC testing
48 MethodsHER2
49 ResultsEighteen
50 adenocarcinoma
51 alpha (TOP2A) genomic status
52 amplification
53 analysis
54 anthracyclines
55 assessment
56 benefits
57 biomarkers
58 biopsy
59 block
60 breast cancer
61 cancer
62 chemotherapy
63 choice
64 clinical-pathologic features
65 diagnostic biopsy
66 disease-free survival
67 epirubicin
68 epirubicin-based chemotherapy
69 error
70 expression
71 features
72 findings
73 fluorescent
74 gastroesophageal adenocarcinoma
75 gene amplification
76 genomic status
77 heterogeneity-related issues
78 hybridization
79 immunohistochemistry
80 impact
81 implications
82 improved disease-free survival
83 independent prognostic biomarker
84 issues
85 multiple resection specimens
86 optimal choice
87 overall survival
88 pairs
89 patients
90 pitfalls
91 positivity
92 possible pitfalls
93 postoperative epirubicin-based chemotherapy
94 procedure
95 prognostic biomarker
96 prognostic impact
97 prognostic implications
98 protein expression
99 rate
100 resectable gastroesophageal adenocarcinoma
101 resection specimen
102 resection specimens
103 respect
104 risk
105 same resection specimen
106 samples
107 sections
108 situ hybridization
109 specimen
110 specimens
111 status
112 subgroup of patients
113 subgroups
114 surgical procedures
115 surgical samples
116 survival
117 testing
118 tissue sections
119 tumor blocks
120 whole tissue sections
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