Based on epidemiological, clinical, and preclinical data, lung carcinogenesis can be distinctive in women, suggesting that women should be treated differently depending on the expression of various specific biomarkers. We aimed to describe the hormonal and genetic profile of lung cancer in both men and women to identify gender specificities. Primary lung-tumor tissues from surgically treated patients, (50 men, 50 women) were analyzed and compared for expression of estrogen receptors (ER) α and β, progesterone receptors (PR), epidermal growth-factor receptor (EGFR), and HER2 (for EGFR and K-Ras mutations). These data were combined with clinical and outcome data. Fewer women with lung cancer were smokers (p=0.001) and they smoked fewer cigarettes (p=0.001). We observed a higher rate of EGFR mutations (p=0.02) and ERα expression (p=0.006) in women. ERβ and EGFR were also expressed more frequently in women (p=0.29 and p=0.16). HER2 was overexpressed regardless of gender in three men and two women. K-Ras was mutated in 16% of both men and women. Interestingly, there was a positive link between EGFR expression and expression of ERα (p=0.028) and ERβ (p=0.047) in both men and women. Expression of ERα was associated with improved disease-free survival (p=0.007). Our findings provide further evidence on the specificities of lung cancer in women. The differential expression of specific biomarkers, which could be targeted by therapy, favors the development of gender-based treatment guided by biomarker expression.
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