Human Epidermal Growth Factor Receptor 2 (HER2) Expression by Immunohistochemistry and Its Clinical Significance in Hepatocellular Carcinoma: A Single-Center Analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is a member of the tyrosine kinase receptor family. It has been identified as an oncogene and is associated with poor outcomes in multiple tumor types. In hepatocellular carcinoma (HCC), there are contradictory data regarding the HER2 expression and its role in tumor development and progression. Some studies have identified HER2 expression as an early event during tumorigenesis, which decreases with progression and metastasis. Additional data provided evidence that treatment with anti-HER2 therapy resulted in local response and reduction in the metastasis rate in HCC mice models.

METHODS: Patients with histological diagnoses of HCC between 2010 and 2020 were included. HER2 staining was performed by immunohistochemistry (IHC), and scoring was done in accordance with the gastric cancer guidelines as 0, 1+, 2+, and 3+. Clinicopathological features were accessed by medical records. This study aims to evaluate HER2 expression by IHC in HCC and to correlate this expression with some clinicopathological features such as Barcelona Clinic Liver Cancer (BCLC) staging, number of hepatic lesions, alpha-fetoprotein level, underlying liver disease, presence of liver cirrhosis, Child-Pugh score, and tumor recurrence.

RESULTS: A total of 57 specimens from 54 patients were included. Of the patients, 85% were men, and the median age at diagnosis was 71 years (interquartile range: 59-75 years). Regarding stage, 61% were at stage 0-A of BCLC. Of the patients, 57% had a solitary HCC nodule. Concerning treatment, surgery was performed in 50% of the patients. HER2 expression was identified in seven patients: five in the membrane and two in the cytoplasm. Concerning the membrane staining, HER2 expression was scored as 1+/2+ in 7.4% (n = 4 patients). Of the patients with HER2 expression, four had a BCLC stage of 0-A and a single HCC nodule; alpha-fetoprotein was <400 ng/mL in all cases. There was no correlation to clinicopathological features. In one patient with HER2 2+ expression at diagnosis, this expression was not identified at tumor progression. Median disease-free survival in HER2 with IHC scores 1+/2+ and cytoplasmatic was 38 months versus 22 months in HER2 with a score of 0 (p = 0.604).

CONCLUSIONS: HER2 expression is a rare event in HCC. It was not possible to identify any relation to clinicopathological features. However, when we relate our data to previous trials, HER2 appears to be an early event in the course of HCC.