According to a study, the overexpression of human epidermal growth factor 2 (HER2) in both cytology and surgical pathology specimens among patients with non-small cell lung cancer (NSCLC) can be used to identify those patients who would benefit from HER2-targeted therapies.

These data were first presented by Olabisi Afolayan-Oloye, MD, MPH, Temple University Hospital, Philadelphia, Pennsylvania, at the 2025 College of American Pathologists Meeting (CAP25) in Orlando, Florida.

As Dr Afolayan-Oloye et al, explained HER2 alterations “have been identified as oncogenic drivers and potential therapeutic targets in lung cancers.” Using immunohistochemistry (IHC), high HER2 protein expression can be identified on cytology or surgical pathology specimens. An IHC score of 3 (IHC3), which is strongly positive and indicates “the presence of HER2 gene amplification,” can be confirmed via genetic testing methods, such as florescence in situ hybridization (FISH).

Study authors performed a database search for cases of cytology and surgical pathology samples diagnosed with NSCLC that are reflexively tested for HER2 to identify those with overexpression of HER2 with IHC3. Dr Afolayan-Oloye et al commented that this score “is defined as cancer cell cluster consisting of > 5 neoplastic cells with a strong complete basolateral, or lateral membranous reactivity irrespective of the percentage of cancer cells positive.”

There were 6 cases from 6 different patients that were identified as HER2 overexpression with IHC3. Gene sequencing identified TP53 (n = 4), KRAS (n = 3), SMARCA4, KMT2A, and EGFR (n = 1 each) mutations. There were no cases identified on gene sequencing to have HER2 mutations.

Dr Afolayan-Oloye et al concluded “HER2 overexpression in cytology and surgical pathology lung specimens” among patients with NSCLC “is indicative of HER2 gene amplification and can identify patients who would benefit from HER2-targeted therapies that have been FDA approved.”

Source:

Afolayan-Oloye O, Akhtar I, and Gonzalaez MF. Overexpression of HER2 immunohistochemistry in non-small cell lung cancer is a target for therapy. Presented at CAP25 Meeting. September 13-16, 2025; Orlando, FL. Poster # 117