The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, has been clinically applied for the treatment of a variety of tumors with EGFR overexpression. A phase II clinical study of erlotinib (NCIC IND-148) for recurrent or metastatic endometrial carcinoma (EC) resulted in an unfavorable result. However, in that study, the expression levels of EGFR were not accurately analyzed. Thus, the aim of this study was to re-examine the efficacy of erlotinib in EC cells by utilizing in vitro and in vivo models. Tissue samples obtained from patients histologically diagnosed with EC of the uterine corpus were subjected to immunohistochemistry and RT-PCR to determine the protein and mRNA expression levels of EGFR. Western blot and WST-1 assays of EGFR siRNA-transfected HEC-1A, KLE, and Ishikawa cells were used to evaluate the efficacy of erlotinib in tumor cell lines expressing different EGFR levels. Furthermore, HEC-1A and Ishikawa cells were implanted into athymic mice treated with either erlotinib or trastuzumab. At our institution, 20.9 % of endometrial cancer patients with low grade endometrioid histology have been diagnosed as stage III and IV. Immunohistochemical analysis and RT-PCR revealed the presence of significant EGFR and EGFR mRNA expression in low-grade endometrioid carcinoma in comparison with high-grade endometrioid carcinoma. In vitro study, WST-1 assay and Western blot analysis revealed that EGFR expression levels were correlated with tumor cell viability. Erlotinib reduced the proliferation of HEC-1A expressing high levels of EGFR, while trastuzumab showed similar effect in Ishikawa cells dominantly expressing human epidermal growth factor receptor type2 (HER2). In vivo erlotinib decreased tumor growth in mice xenografted with HEC-1A cells, whereas this tumor-growth inhibition was not observed in trastuzumab-treated mice xenografted with Ishikawa cell. EGF contributed to tumor proliferation in EC cell lines along with EGFR expression in vitro. Erlotinib also demonstrated anti-tumor effects in xenograft mice models. Our results suggest that erlotinib continues to have clinical usefulness in specific cases, after taking into consideration the EGFR expression levels.

Tate S, et al. J Gynecol Oncol. 2025 Mar;36:e80. https://doi.org/10.3802/jgo.2025.36.e80

Objective: Endometrial cancer (EC) is one of the most common cancers in women, and its incidence is increasing worldwide. The prognosis of recurrent and advanced cancer remains poor because treatment options are limited. Ubiquitin C-terminal hydrolase-L1 (UCHL1) is associated with the progression of several cancers including EC. In this study, we analyzed the function of UCHL1 in EC progression. Methods: UCHL1 expression in the serum of patients with EC was measured using an enzyme-linked immunosorbent assay. Changes in cell migration and invasion were analyzed in UCHL1-overexpressing or UCHL1-knockdown cells (UCHL1-OE/UCHL1-KD) using wound-healing and transwell assays. Messenger RNA expression of epithelial–mesenchymal transition (EMT)-related genes in each cell was detected using quantitative real-time polymerase chain reaction (qRT-PCR). UCHL1 and EMT marker proteins were detected with Western blotting and an immunofluorescence assay (IFA). Results: Serum UCHL1 expression was significantly elevated in patients with metastases. Wound-healing assays and transwell assays showed that UCHL1 could promote cell migration and invasion. These effects were suppressed by UCHL1 knockdown and inhibition. UCHL1 overexpression modulated the expressions of EMT-related molecules in EC cells at the mRNA and protein levels. Furthermore, IFA analysis showed that changes in EMT-related molecules were consistent with lesions of UCHL1 expression. Conclusions: This study revealed that UCHL1 could contribute to promoting cell migration and invasion. These results may be associated with EMT regulation in EC cells.