The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature.
BACKGROUND
Human epidermal growth factor receptor-2 (HER2) is regarded as an important and promising target in the treatment of HER2-positive breast cancers. However, the correlation of clinicopathological characteristics and prognostic significance of HER2 overexpression in gastric cancer patients remains unclear. Our aim was to clarify this issue.


METHODS
Embase, PubMed, and the Cochrane Library were searched for relevant articles published up to May 2016. Outcomes of interest contained sex, age, tumor size, tumor site, tumor node metastasis (TNM) stage, distant metastasis, lymph node metastasis, Lauren's classification, differentiation grade, lymphovascular invasion, neural invasion, and multivariate analysis data for overall survival.


RESULTS
A total of 41 studies of 17,494 gastric cancer patients were identified with HER2 test. HER2 positive rate was 19.07% (95% CI = 9.16, 28.98). There existed statistical significance between HER2 overexpression and patients' prognosis (RR = 1.47, 95% CI = 1.09, 1.98). Male patients (OR = 1.48, 95% CI = 1.34, 1.65), proximal tumors (OR = 1.25, 95% CI = 1.07, 1.47), intestinal-type tumors (OR = 3.37, 95% CI = 2.54, 4.47), advanced stage cancers (OR = 1.35, 95% CI = 1.10, 1.66), lymph node metastasis (OR = 1.26, 95% CI = 1.14, 1.41), well-differentiated cancers (OR = 1.79, 95% CI = 1.15, 2.76), and distant metastasis (OR = 1.91, 95% CI = 1.08, 3.38) were correlated with higher HER2 expression rates. However, no statistical differences existed in age, tumor size, lymphovascular invasion, or neural invasion. Subgroup analysis revealed that HER2 expression rates reported in articles from Asian (19.52%) countries were quantitatively higher than those from European (16.91%) areas. Results were consistent with those reports that define HER2 status according to trastuzumab for gastric cancer (ToGA) criteria.


CONCLUSIONS
This study showed that HER2 overexpression was associated with poor prognosis in gastric cancer patients. HER2 positive rates may be associated with sex, tumor site, TNM staging system, distant metastasis, lymph node metastasis, Lauren's classification, and differentiation grade in gastric cancer patients. The HER2 expression rate in Asians may be higher than that in Europeans. This study offers a convenient way for doctors to select patients for relevant HER2 detection and following treatment.
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 110001, Shenyang, Liaoning, China.
Yu-Ying
YY
Lei
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 110001, Shenyang, Liaoning, China.
Jin-Yu
JY
Huang
Department of Evidence Based Medicine, First Affiliated Hospital of China Medical University, 110001, Shenyang, Liaoning, China.
Qiong-Rui
QR
Zhao
International Education School, China Medical University, 110001, Shenyang, Liaoning, China.
Nan
N
Jiang
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 110001, Shenyang, Liaoning, China.
Hui-Mian
HM
Xu
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 110001, Shenyang, Liaoning, China.
Zhen-Ning
ZN
Wang
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 110001, Shenyang, Liaoning, China.
Hai-Qing
HQ
Li
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 110001, Shenyang, Liaoning, China.
Shi-Bo
SB
Zhang
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 110001, Shenyang, Liaoning, China. sunzheyida@163.com.
Zhe
Z
Sun
D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
Gastric cancer; HER2/neu; Meta; Prognosis