Oestrogen receptor beta over expression in males with non-small cell lung cancer is associated with better survival

Adenocarcinoma of the lung is more frequent in females than in males and the association with smoking is less pronounced than for the other histological subtypes of lung cancer. Oestrogen induction of cell proliferation has been found in breast adenocarcinomas, and since oestrogen receptors (ER) have been demonstrated in lung tumours, a similar role of oestrogens in the development of lung cancer has been suggested. We examined the expression of ERalpha, ERbeta and progesterone in a well defined cohort of patients with NSCLC with more than 15 years of follow up, and related the results to gender and survival.

Paraffin embedded, histological material was collected from 104 patients (71 men and 33 women), operated in the period 1989-1992 for NSCLC (56 squamous cell carcinomas, 40 adenocarcinomas and 8 large cell carcinomas). ERalpha, ERbeta and progesterone were immunohistochemically analysed. Staining frequency and intensity was scored semi-quantitatively. A tumour was defined as positive when more than 10% of the tumour cells were positive with at least a weak nuclear staining. Kaplan-Meier survival curves were generated to evaluate the significance of ERalpha, ERbeta and progesterone expression for the prognosis.

ERbeta positivity was demonstrated in 69% (72 of 104) of the tumours. There was no statistically significant correlation between ERbeta positivity and age, gender, stage, or histology. After adjusting for gender, age, stage at diagnosis and histology there was no difference in survival between subjects with ERbeta positive and ERbeta negative tumours. When stratifying by gender women with ERbeta-negative tumours had a non-significant (P=0.26) decrease in mortality compared with women with ERbeta positive tumours. In contrast, men with ERbeta positive tumours had a significantly reduced mortality (P=0.035) compared to men with ERbeta negative tumours. Using multivariate regression analysis the interaction between gender and positive ERbeta staining was the only significant prognostic factor. There was no correlation between the ERalpha immunohistochemical staining and any of the clinical variables, including survival. None of the 104 patients had tumours positive for progesterone.

The presence of ERbeta in a tumour seems to be a positive prognostic factor for men with non-small cell lung cancer. The finding confirms another recent study and suggests that the relation between oestrogens and lung cancer be investigated further.