Prognostic Value of Her2/neu Expression in Gastrointestinal Stromal Tumors: Immunohistochemical Study

Abstract

Background:Gastrointestinal stromal tumor (GIST) is a relatively rare type of neoplasms. In Egypt, it represents 2.5% of gastrointestinal tumors and 0.3% of all malignancies. Most of the GISTs develop in the stomach.Aim:To reveal the significance of Her2/neu immunohistochemical expression in GIST and its correlation with other histopathologic parameters and tumor relapse after regular follow-up.Patients and methods:This study is a retrospective and prospective cohort. It included 32 patients with GISTs, who were resectable with no distant metastasis. Immunohistochemical staining by Her2/neu was performed after complete surgical resection of the tumors with preservation of the pseudocapsule.Results:In total, 53.1% of cases were men and 46.9% women. Tumors were classified into low-risk (25%), intermediate-risk (21.9%), and high-risk groups (53.1%). Her2/neu expression was negative in 56.3% of GISTs and positive in 43.7%. Its expression was significantly correlated with risk grade (P = .04), tumor size (P = .001), mitotic count (P = .00), and increased risk of relapse (P = .00). Furthermore, tumor relapse was significantly correlated with the tumor mitotic counts (P = .00). Using kappa agreement test, it showed that 4 mitotic counts/50 high-power fields (HPF) was the cutoff value with which the tumor might be associated more with relapse, with 83% sensitivity, 70% specificity, and P value of .003.Conclusions:Her2/neu might be used as an independent prognostic marker for tumor recurrence after complete resection of GIST, and the cutoff value of mitotic count that might predict tumor relapse is 4/50 HPF. However, more clinical studies with greater number of cases with fluorescent in situ hybridization integration are recommended.

Chromosomal instability and a deregulated cell cycle are intrinsic features of high‐risk gastrointestinal stromal tumours with a metastatic potential

“…ERBB2 is another upstream regulator observed to be upregulated in the metastatic samples and is a major driver of cell proliferation and angiogenesis. In a previous study, ERBB2 protein (Her2/neu) expression has been significantly correlated with risk grade, tumour size, mitotic count, and increased risk of relapse in primary GIST [ 61 ]. Overexpression of the upstream regulator MYC has previously been shown to reversibly induce and maintain CIN, contributing to aneuploidy, tumorigenesis, and tumour evolution [ 62 ].…”

Role of Her-2 in Gastrointestinal Tumours beyond Gastric Cancer: A Tool for Precision Medicine

“…Likewise, another trial including 94 GIST failed to show gene amplification for HER2 [90]. However, a small Egyptian study including 32 patients showed a 43.7% positivity in HER2 status [91]. Additionally, it reported that high-risk grade, tumor size, mitotic count, and increased risk of relapse were significantly correlated with HER2 positivity.…”