Expression and significance of Her2 and Ki-67 in gastric adenocarcinoma without distant metastasis: a cohort study
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RESEARCH ARTICLE
Expression and significance of Her2 and Ki‑67 in gastric adenocarcinoma without distant metastasis: a cohort study Zhijian Wei1†, Lei Huang1*† , Xinyue Zhang2 and Aman Xu1*
Abstract Background: The significance of human epidermal growth factor receptor 2 (Her2) and nucleus-associated antigen Ki-67 expression remains controversial in gastric adenocarcinoma (GaC). The aim of this study was to investigate the expression and clinicopathologic and prognostic significance of Her2 and Ki-67 in resected GaC without distant metastasis. Methods: Malignant tissues and clinicopathologic data were obtained from 195 patients with resected non-metastatic GaC. Immunohistochemistry staining was performed to examine the expression of Her2 and Ki-67; their association with clinicopathologic factors were investigated using logistic regression, and their association with survival was explored using Kaplan–Meier analysis and Cox proportional hazards regression. Results: Her2 was majorly expressed in cell membrane and Ki-67 in cell nucleus in non-metastatic GaC. Stronger Her2 expression was significantly associated with better tumor differentiation, neurovascular invasion, less advanced pathological tumor (pT) stage, and more advanced pathological node (pN) stage; while Ki-67 expression was not significantly associated with any investigated clinicopathologic factors. Patients with both negative Her2 and negative Ki-67 expression had poorer tumor differentiation, and more advanced pT and pathological tumor-node-metastasis (pTNM) stages; the association with pT and pTNM stages were further confirmed by multivariable analyses, especially in node-negative disease. Her2 or Ki-67 alone was not significantly associated with pTNM stage. A strongly positive (+++) Her2 expression was associated with poorer survival in multivariable analysis only (P = 0.047); while Ki-67 or combined expression was not significantly associated with prognosis. Conclusions: In non-metastatic GaC, Her2 expression and combined expression of Her2 and Ki-67 were associated with several clinicopathologic factors including tumor differentiation and stage, and only a +++ Her2 expression was associated with poorer prognosis in multivariable analysis with marginal significance in this study; while Ki-67 alone had both limited clinicopathologic and prognostic values. Keywords: Gastric adenocarcinoma, Human epidermal growth factor receptor 2 (Her2), Nucleus-associated antigen ki-67, Cohort study
*Correspondence: [email protected]; [email protected] † Zhijian Wei and Lei Huang contributed equally to this work 1 Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei 230022, Anhui, China Full list of author information is available at the end of the article
Background Gastric cancer, the majority of which is gastric adenocarcinoma (GaC), is one of the most prevalent and lethal digestive malignancies worldwide [1, 2]. Although the diagnosis and treatment modalities have improved, th
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