Expression patterns and clinical significance of estrogen receptor in non-small cell lung cancer

Lung cancer death remains the highest among all malignancies. Gender differences show women have an increased cancer incidence while men have worse outcomes. These observations identified that some lung carcinomas express estrogen receptors (ER). This is a promising target as antiestrogen drugs can reduce tumors and improve survival. However, there is a limited understanding of ER distribution and its clinical significance to properly design antiestrogen drug clinical trials. Thus, we comprehensively analyzed ERα and ERβ expression patterns by gender, cancer cell type, and receptor location in lung cancer.

We conducted a systematic review using the PubMed database from all-time through October 2022, using MeSH terms with the keywords "lung cancer," "estrogen receptor," and "immunohistochemistry." We identified 120 studies with 21 reports being evaluated based on our inclusion criteria.

We examined 4874 lung cancers from 5011 patients. ERβ is the predominant form of ER expressed, mainly found in the nucleus. The ERβ positivity rate is 51.5% in males versus 55.5% in females and was not statistically different. In contrast, ERα is predominately extranuclear in location, and ERα expression varies by gender. Males had a positivity rate of 31% versus 26.6% in females, which is statistically different. ERα is associated with a worse prognosis in some studies, while it had no effect in others. Overall, ERβ was associated with a better prognosis.

We characterized ER expression patterns in 4874 lung cancers. Over 50% expressed ERβ with equal rates in both sexes and was associated with a better prognosis. ERα expression was slightly higher in males (31%) than females (26.6%) and was associated with a poor prognosis. Our findings suggest estrogen signaling may be a promising drug target in lung cancer.