Her2 Expression as a Prognostic Factor in Metastatic Gastric Cancer

Aguiar, Pedro Nazareth; Neto, Ricardo Artigiani; Forones, Nora Manoukian

doi:10.1590/s0004-28032016000200003

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…HER-2 overexpression or amplification has been associated with a more aggressive disease, a poor clinical prognosis. 23,24 Our study showed that elevated serum HER-2 ECD could be associated to a more aggressive clinical course. There are several explanations for the link between HER-2 ECD level and PFS.…”

Section: Discussionmentioning

confidence: 69%

Elevated serum HER‐2 predicts poor prognosis in breast cancer and is correlated to ADAM10 expression

et al. 2019

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Human epidermal growth factor receptor‐2 (HER‐2) overexpression in breast tumor tissues is associated with a poor prognosis but may benefit from treatment with trastuzumab. The extracellular domain (ECD) of HER‐2 can be measured in serum and which has been a new inspection item in clinical laboratory of several hospitals. However, whether serum HER‐2 ECD can be a marker of HER‐2 status in tumor tissues still confused clinicians. This study is a retrospective observation to explore the correlation between serum HER‐2 ECD shedding and tissue HER‐2 status in breast cancer patients. Meanwhile, we will further uncover the potential clinical significance of serum HER‐2 ECD detection. A total of 545 unselected breast cancer patients from Fudan University Shanghai Cancer Center were enrolled in this study. At primary diagnosis without any treatment, serum HER‐2 ECD was measured on ADVIA Centaur assay; meanwhile, tissue HER‐2 from core needle biopsy was tested through immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). We showed that serum HER‐2 ECD concentration was related to tissue HER‐2 status. Nevertheless, 36.9% of patients with tissue HER‐2 overexpression had low levels of HER‐2 ECD shedding (<15 ng/mL) in serum. Here, we demonstrated that HER‐2 ECD shedding was also associated with protein expression and alpha‐secretase activity of a disintegrin and metalloproteinase 10 (ADAM10) using tumor tissues and cell lines. Progression‐free survival (PFS) data from breast cancer patients in TNM phase II and III with tissue HER‐2 IHC 3+ were analyzed using Kaplan‐Meier plotter. The patients with serum HER‐2 ECD above 15 ng/mL had lower progression‐free survival than those with serum HER‐2 ECD <15 ng/mL. Thus, serum HER‐2 ECD could be a biomarker to identify the subgroup of poorer outcome among HER‐2 overexpression breast cancer patients. Inhibition of ADAM10 activity may have potential therapeutic benefit for this most aggressive tumor subgroup.

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Section: Discussionmentioning

confidence: 69%

Elevated serum HER‐2 predicts poor prognosis in breast cancer and is correlated to ADAM10 expression

et al. 2019

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“…Fornaro et al (2011) reported that intestinal-type gastric cancers show more HER-2 positivity compared to diffuse-type gastric cancers. In their study, Junior et al (2016) reported that HER-2 overexpression was a poor prognostic factor in metastatic gastric cancer patients. In their meta-analysis study, Lei et al (2017) stated that genetic and geographic factors were effective in HER-2 expression, and HER-2 positivity was associated with gender, TNM stage, distant organ metastasis, lymph node metastasis, and Lauren classification.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of HER-2 Expression in Gastric Cancer

Özmen

2021

Black Sea Journal of Health Science

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In gastric cancers we purposed to examine the relationship between age, gender, invasion depth, lymph node metastasis, lymphovascular invasion, Lauren's classification, presence of perineural invasion and the expression of Human Epidermal Growth Receptor (HER-2) by immunohistochemical (IHC) and dual-color silver-enhanced in situ hybridization (D-SISH) method. In our study, 242 gastric resection materials that were studied HER-2 by IHC and/or D-SISH method referred to our department between January 2014 and December 2017 for malignancy were included. The relationship between HER-2 expression rate and prognostic parameters was investigated. No statistical relation was found between age and gender and HER-2 positivity in either method. No statistically significant results were obtained between lymphovascular invasion, lymph node metastasis, presence of perineural invasion, depth of invasion and Lauren classification, and HER-2 positivity by immunohistochemical and D-SISH method. In our study, no statistically significant results were obtained between important prognostic parameters and HER-2 positivity with either IHC or D-SISH method. In 24.1% of the cases that were HER-2 positive by IHC, positivity was not observed with the D-SISH method. Also, 20.8% of the cases reported as immunohistochemically uncertain (equivocal) were seen as positive by the D-SISH method. Based on all these results, we would like to state that HER-2 positivity / negativity determined by IHC can be changed by the D-SISH method. In addition, although it was shown in our study that HER-2 has no prognostic significance in gastric carcinomas, it is reported in studies in the literature that the addition of Trastuzumab to chemotherapy increases survival. For this reason, we think that it would be more beneficial to apply the IHC and D SISH method together to obtain the true HER-2 result.

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“…Most cases of gastric cancer are adenocarcinomas (3,4); the main risk factors of gastric adenocarcinoma are age >60 years (3,5), male gender (5-7), low socioeconomic status, occupational exposure (high temperatures and dust, asbestos, X and gamma radiation, inhalation of hexavalent chromium, and inorganic lead compounds) (8), smoking, alcohol consumption, obesity, gastroesophageal reflux disease, Helicobacter pylori infection, high consumption of salt and nitrites, and low consumption of fresh fruit and vegetables (3,4,9). Prognostic factors include the presence of comorbidities (10, 11), smoking, alcohol consumption (12), clinical stage (13-15), and clinical and molecular characteristics of the tumors (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Gastric adenocarcinoma: 1-year overall survival, disability-adjusted life years, years of life lost, and prognostic factors—a single-institution experience

Tiengo

Fernandes²,

Curado³

2022

Front. Oncol.

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ObjectiveTo analyze factors affecting 1-year overall survival and burden of gastric adenocarcinoma in a single-institution cohort.MethodsA prospective cohort study of gastric adenocarcinoma patients from a cancer center in São Paulo, Brazil, was conducted between February 2016 and July 2019. Overall survival was analyzed at 12 months post-diagnosis using the Kaplan–Meier method. A log-rank test was applied to compare curves. Sociodemographic and clinicopathological features were assessed to detect prognostic factors using univariate and multivariable Cox regression analyses to calculate hazard ratio (HR) and its confidence intervals (CIs). Disability-adjusted life years (DALY) constituted the sum of years of life lost (YLL) plus years lived with disability (YLD). YLL represented the sum of years lost before the age of 76.6 years. YLD was calculated as the number of cases multiplied by the duration and burden of the disease. YLL per death was calculated as the mean YLL for each individual.ResultsOverall survival at 1-year follow-up was 80.8%. The multivariable model adjusted for age and sex identified cerebrovascular disease (HR 8.5, 95% CI 3.3–21.8), stage III/IV (HR 5.7, 95% CI 2.3–13.7), diabetes (HR 3.2, 95% CI 1.5–6.6), and<9 years of education (HR 2.9, 95% CI 1.5–5.8) as prognostic factors. Out of the 214 treated cases, there was 700.72 DALY during the first year, of which 90.55% corresponded to YLL and 9.45% to YLD. The average YLL per death was 15.48 and was higher among women (19.24 YLL per death).ConclusionAt a single cancer center, 1-year overall survival probability was approximately 80% in patients with gastric adenocarcinoma. Patients with a higher risk of death had cerebrovascular disease, advanced clinical staging, diabetes, and/or lower educational level. Approximately 700 years of DALY was documented, with women having the highest YLL per death. Because this study was conducted at a single cancer center, the results might not be representative of a general population. To the best of our knowledge, this study was the first to assess gastric adenocarcinoma DALY, YLL, and YLL per death in the first year of follow-up in a hospital cohort in Brazil.

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Her2 Expression as a Prognostic Factor in Metastatic Gastric Cancer

Cited by 7 publications

References 18 publications

Elevated serum HER‐2 predicts poor prognosis in breast cancer and is correlated to ADAM10 expression

Elevated serum HER‐2 predicts poor prognosis in breast cancer and is correlated to ADAM10 expression

Prognostic Significance of HER-2 Expression in Gastric Cancer

Gastric adenocarcinoma: 1-year overall survival, disability-adjusted life years, years of life lost, and prognostic factors—a single-institution experience

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