Prognostic value of HER2 expression in cervical adenocarcinoma:  A retrospective cohort study

Human epidermal growth factor receptor 2 (HER2) is an important therapeutic target in various types of cancer, although the prognostic value and therapeutic potential of HER2 in cervical adenocarcinoma are still underexplored. The present study aimed to examine the association between HER2 expression levels and prognosis in cervical adenocarcinoma, offering new insights into targeted therapies for HER2-expressing cervical adenocarcinoma. A total of 179 patients with cervical cancer who received surgery were included, and HER2 status in surgical specimens of the included patients were assessed using two classification methods: Immunohistochemistry (IHC) alone and traditional combined IHC/fluorescence in situ hybridization (FISH). IHC alone was used to categorize patients into the HER2 zero expression (IHC 0) and HER2 expression (IHC 1+, 2+ and 3+) groups, while traditional combined IHC/FISH classified the HER2 expression as negative (IHC 0 and 1+ or IHC 2+/FISH-) or positive (IHC 3+ or IHC 2+/FISH+). Kaplan-Meier survival analysis and log-rank tests were used to assess the patients' survival prognosis. A Cox proportional hazards regression model was used to identify independent prognostic factors. The HER2 expression rate was 44.1% (79/179) according to IHC alone, while 5.0% (9/179) were classified as HER2-positive according to the traditional method. HER2 expression was significantly associated with advanced International Federation of Gynecology and Obstetrics stages, higher rates of lymph node metastasis, vascular or perineural invasion, elevated cancer antigen 125 levels and increased recurrence rate (P<0.05). Moreover, HER2 expression was significantly associated with shorter progression-free survival (PFS) time [51.02±2.75 vs. 56.01±2.22 months; hazard ratio (HR), 0.559; 95% confidence interval (CI), 0.313-0.998; P=0.049]. Additionally, programmed death-ligand 1 expression levels were significantly higher in HER2-expressing patients who died (P=0.039). When HER2 status was assessed using the traditional combined IHC/FISH method, HER2 positivity was significantly associated with poorer PFS time (36.44±7.85 vs. 55.17±1.78 months; HR, 0.125; 95% CI, 0.03033-0.5156; P=0.004). In conclusion, classification of HER2 status in patients with cervical adenocarcinoma using IHC alone may provide a promising method for predicting patient outcomes and optimizing therapeutic strategies to improve treatment efficacy.