Preferential HER2 expression in liver metastases and EGFR expression in peritoneal metastases in patients with advanced gastric cancer

Saito, Takuya; Nakanishi, Hayao; Mochizuki, Yoshinari; Ito, Seiji; Ito, Y.; Misawa, Kazunari; Yatabe, Yasushi; Yamamichi, Keigo; Kondo, Eisaku

doi:10.1007/s10120-014-0417-4

Cited by 27 publications

(21 citation statements)

References 29 publications

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“…Positive conversion was more frequent than negative one (10.8 % vs. 5,4 %) [19]. These results were also confirmed by other recent reports conducted on Asiatic patient cohorts [20][21][22].…”

Section: Discussionsupporting

confidence: 94%

HER2 Status in Gastric Cancer: Comparison between Primary and Distant Metastatic Disease

Amato

Perrone

Righi

et al. 2016

Pathol. Oncol. Res.

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HER2 (human epidermal growth factor receptor-2) assessment in histological samples of gastric cancer is essential to determine which patients might benefit from trastuzumab therapy. HER2 is often evaluated in primary tumor even if trastuzumab therapy is used to treat metastatic disease. However, the exact relationship in terms of HER2 status between primary and metastatic tumors has not been fully clarified. We aimed to evaluate the HER2 status concordance between primary gastric cancer and corresponding distant metastasis. HER2 status was evaluated by IHC (immunohistochemistry) and/or FISH ( fluorescence in situ hybridization) in 41 patients in primary gastric cancer and in paired metastasis. HER2 was assessed according scoring criteria applied in clinical approach. HER2 positivity was found in 14,6 % primary tumors and in 24,4%corresponding metastasis. HER2 concordance rate between primary and metastasis was 80,5 % (K-value = 0,388). Eight/41 (19,5 %)cases resulted discordant: 6 patients with metastatic HER2 positive lesions were found HER2 negative in primary cancers while 2 patient HER2 positive in primary lesion showed a negative conversion in metastasis. Our results showed a good concordance in terms of HER2 status between primary and metastatic lesions, as well as in biopsy and surgical removed specimens. However, the higher rate of HER2 positive status found in metastatic lesions underlined the importance of HER2 assessment in all samples obtained from different sites of gastric cancer disease.

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Section: Discussionsupporting

confidence: 94%

HER2 Status in Gastric Cancer: Comparison between Primary and Distant Metastatic Disease

Amato

Perrone

Righi

et al. 2016

Pathol. Oncol. Res.

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“…In contrast, other studies that queried discordance of ERBB2 within distinct regions of the PT found discrepancies in only 12% of cases (27,28), or that patients with metastatic GEA with negative ERBB2 testing from a biopsy of the PT showed ERBB2 positivity in the metastatic disease in only 5.7% of cases (29). In addition, other studies have shown 87.5% to 98.5% concordance of ERBB2 between PT and paired metastatic sites (30,31). Based upon these existing data, new 2016 guidelines for assessment of ERBB2 status in GEA recommend that testing be performed on a single site, either the PT or metastases, stating that the totality of literature does not suggest common heterogeneity of ERBB2 between sites (32).…”

Section: Introductionmentioning

confidence: 91%

Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

et al. 2018

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Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited effi cacy. A potential reason for the failure of such therapies is that genomic profi ling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, fi nding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed signifi cant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplifi cation profi les commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifi cations not detected in PT sampling. Lastly, we profi led paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profi ling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profi ling to enhance selection of therapy. SIGNIFICANCE:We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profi ling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1);[37][38][39][40][41][42][43][44][45][46][47][48]

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“…Another situation that seems to increase the incidence of HER2+ is the proximal third tumors [22, 23], but such a site accounts for only one-third of the sample of our patients. Moreover, some studies [24] suggest an association between greater expression of HER2 and the presence of hepatic metastases. Nevertheless, no patients in this situation were included in our study, as we understand that both the metastatic disease and the residual tumor following palliative resections are situations which clearly compromise the survival time and interfere with the analysis of the results, as one of the objectives of this study was to verify the incidence of HER2 expression in gastric cancer and its possible relationship with survival.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Expression of the Human Epithelial Receptor 2 (HER2) in Gastric Carcinoma

Filho

Kassab

Claro

et al. 2016

The Scientific World Journal

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Objective. To evaluate the HER2 expression on gastric adenocarcinoma from a Brazilian population and also to analyze the relations between the receptor and clinical characteristics, as well as the survival status. Materials and Methods. A retrospective analysis was conducted from January of 2008 to July of 2012, considering only gastrectomies with curative intent. Tumors were tested for HER2 status using immunohistochemistry. The relation between HER2 status and clinical aspects, surgical findings, and survival were also analyzed. Results. 222 patients with gastric carcinoma were submitted to surgery during that period, but only 121 (54,5%) were with curative intention. The immunohistochemistry revealed that 4 patients (3,3%) were HER2-positive, 6 patients (4,9%) HER2-undetermined, and 111 patients (91,7%) HER2-negative. There was no statistical concordance between HER2 status and survival or the clinical aspects. Conclusion. The HER2 overexpression rate was very low in this Brazilian population sample and cannot be considered as a prognostic factor.

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Preferential HER2 expression in liver metastases and EGFR expression in peritoneal metastases in patients with advanced gastric cancer

Cited by 27 publications

References 29 publications

HER2 Status in Gastric Cancer: Comparison between Primary and Distant Metastatic Disease

HER2 Status in Gastric Cancer: Comparison between Primary and Distant Metastatic Disease

Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

Evaluation of the Expression of the Human Epithelial Receptor 2 (HER2) in Gastric Carcinoma

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