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Revisiting lung cancer diagnosis: The role of steroid receptors

Lung cancer is the most common malignancy worldwide and is associated with poor prognosis. Re-evaluating the diagnostic criteria of different lung cancer subtypes to include specific steroid receptors should improve treatment and prognosis.
Revisiting lung cancer diagnosis: The role of steroid receptors
Gender seems to be a major determinant of lung cancer impact, histology, evolution, response to therapy and prognosis. This suggests a potential relation to steroid hormones, especially in view of the hormone replacement therapies and contraception strategies followed by a large proportion of the female population.

In addition, since the lung is a primary site for distant metastases of prostate and breast carcinomas, a steroid receptor profiling could help differentiate diagnosis of primary lung tumours from metastatic foci. In this context, the EU-funded SRLUNG (Steroid receptors in non-small cell lung cancer: Diagnostic, prognostic and therapeutic implications) project set out to investigate the prognostic, diagnostic and therapeutic relevance of sex oestrogen receptors (ERs) in non-small cell lung carcinoma (NSCLC).

For this purpose, researchers used a multi-epitope immunohistochemical assay and a novel multiplex ER probe-based transcriptome meta-analysis of a large cohort of NSCLC tumours. Results showed that the wild type ERa was present in only 10 % of cases, while variant receptors prevailed in tumours.

In the lung, ERs localised in extra-nuclear cellular compartments, suggesting alternative modes of action compared to endocrine organs. Compared to normal lungs, NSCLC ERa variant expression depended on tumour histology and not on gender. In addition, NSCLC expressed ERs not encoded by the Esr1 gene, while the expression profile of other types of lung cancer such as adenocarcinoma or squamous cell carcinomas differed.

Taken together, these observations indicate that in NSCLC sex steroid receptors function in a distinct manner from endocrine-related neoplasms. This is of primary importance for the differential diagnosis of lung tumour masses of unknown origin. Furthermore, it could lead to the establishment of novel biomarkers and therapeutic targets.

Related information


Lung cancer, steroid receptors, gender, non-small cell lung carcinoma, oestrogen receptors
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