Retrospective analysis finds uncertain HER2-low survival link in esophagogastric junction adenocarcinoma

A retrospective analysis of 74 patients with resected adenocarcinoma of the esophagogastric junction found that tumors classified as HER2-low were associated with longer overall survival in a Kaplan–Meier analysis, although the association was not statistically confirmed as an independent prognostic factor after multivariate adjustment. HER2-low expression occurred in 20 patients, or 27% of the cohort, while lymph node metastasis was the factor independently associated with overall survival.

The study included patients who had undergone curative surgical resection and whose tumor specimens were classified as HER2-non-amplified. Researchers used immunohistochemistry to divide the tumors into two groups: HER2-null, defined by an immunohistochemistry score of 0, and HER2-low, defined by an immunohistochemistry score of 1+ or 2+ together with negative in situ hybridization. This analysis therefore focused specifically on HER2 expression in resected esophagogastric junction adenocarcinoma, rather than all forms of junction cancer.

HER2-low status was present in 20 of the 74 patients. In the Kaplan–Meier comparison, overall survival was longer in the HER2-low group than in the HER2-null group, with the difference reaching statistical significance at p = 0.01. No significant difference was found for disease-free survival. The results show an association between low HER2 expression and overall survival after surgery, but they do not establish that HER2-low status causes longer survival or prevents recurrence.

Multivariate analysis changed the interpretation of that association. Lymph node metastasis emerged as independently associated with overall survival, whereas the independent prognostic value of HER2-low status was not statistically confirmed. As a retrospective analysis based on a small surgical cohort, the study could identify an observed survival difference but could not fully separate the influence of HER2-low status from other factors associated with patient outcomes. The lack of a statistically confirmed independent effect also limits the strength of any prognostic claim based on HER2-low classification alone.

Among patients who received chemotherapy after recurrence, complete response was recorded in two of four HER2-low patients and none of 17 HER2-null patients. The authors described this result as hypothesis-generating because the groups contained very small numbers of patients. The observation does not demonstrate that HER2-low tumors respond better to chemotherapy after recurrence, nor does it establish a clinical benefit from changing treatment according to low HER2 expression. The principal finding is narrower: in this retrospective cohort, HER2-low tumors were associated with longer overall survival in a univariate survival analysis, but that association did not remain statistically confirmed as an independent prognostic factor.

Subject of Research: Prognostic significance of HER2-low expression in resected esophagogastric junction adenocarcinoma

Article Title: Prognostic significance of low HER2 expression in adenocarcinoma of the esophagogastric junction: a retrospective analysis

Article References: Gokon, Y., Ozawa, Y., Ichikawa, H., Taniyama, Y., Teshima, J., Okamoto, H., Sato, C., Ishida, H., Yamauchi, T., Nagano, S., Kijima, W., Itakura, Y., Fujishima, F., & Kamei, T. (2026). Prognostic significance of low HER2 expression in adenocarcinoma of the esophagogastric junction: a retrospective analysis. BMC Cancer. https://doi.org/10.1186/s12885-026-16858-7

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16858-7

Keywords: HER2-low, esophagogastric junction, adenocarcinoma, overall survival, retrospective analysis, immunohistochemistry, in situ hybridization, lymph node metastasis, Prognostic, significance, HER2, expression