HER2/neu Expression in Low-Grade Serous Ovarian Carcinoma: A Pilot Two-Center Retrospective Study

Background/Objectives: Low-grade serous ovarian carcinoma (LGSOC) is known as an uncommon subtype of cancer with poor response to standard chemotherapy, so novel targets are required. The current study aims to highlight the Human Epidermal Growth Factor Receptor-2 (HER2/neu) immunohistochemical (IHC) expression in LGSOCs. Methods: The study was conducted using 33 cases of LGSOCs from the calendar years 2017–2024. IHC staining was performed using antibody anti-HER2/neu (clone 4B5). HER2/neu scoring was performed based on the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) criteria for breast carcinoma. Results: The mean age of the 33 patients was 46.5 years. International Federation of Gynecology and Obstetrics (FIGO) stage data for patients revealed a predominance of advanced disease: 82.7% (24/29) were in advanced stages. Early stages comprised 17.3% (5/29) of cases. The study did not find HER2/neu overexpression in all cases. In 3.0% of samples (1/33), HER2/neu IHC staining was scored as 1+, and in 6.1% (2/33) of all LGSOCs, ultralow phenotype was observed. Of 23 cases in the HER2-negative group, 6 patients were alive with progressive disease, 1 patient died in 5 months, and 16 were alive with no evidence of disease. Of two patients with the HER2-ultralow phenotype, one was alive with no evidence of disease at 16 months follow-up. Conclusions: The results support the idea that HER2/neu overexpression is exceptionally rare in LGSOC; nevertheless, future trials are essential to fully characterize the spectrum of HER2/neu alterations in LGSOC and to determine definitively whether the rare cases with mutations or ultralow expression could represent a small subgroup that might benefit from specific targeted agents.