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E. Gobbini
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-060 - Non Small Cell Lung Cancer in Women: Identification of Molecular Biomarkers Towards Sex Specific Tailored Treatments (ID 1272)
09:30 - 09:30 | Author(s): E. Gobbini
- Abstract
Background:
Lung cancer is the leading cause of cancer mortality in both men and women in more developed countries, with a four-fold increase in lung cancer in women in US over the past 30 years. This was confirmed in Europe where, in the last 5 years, lung cancer mortality fell in men (−6%) and increased in women (+7%). Several studies documented sex differences in lung cancer in terms of clinical presentation, survival, pathological patterns and treatment related toxicities; younger age at diagnosis, higher frequency of adenocarcinoma histology, different metabolism of tobacco-related carcinogens, differential gene expression are commonly seen in women. Furthermore, previous studies showed in female gender the expression of functional aromatase enzyme in lung tumor tissues as well as the interaction between Estrogen Receptors (ERs) and Epidermal Growth factor Receptor (EGFR) pathways in lung cancer cells. The aim of this study is to collect a prospective series of advanced stage non small cell lung cancers (NSCLC), to identify, through the Next Generation Sequencing (NGS) technology, potential gender sex differences of selected tumor-associated genes, assessing their both mutational status and gene expression levels.
Methods:
One hundred patients, including 50 women and 50 men, with newly diagnosed stage IV NSCLC will be prospectively enrolled. Smoking history, clinical and anamnestical data will be collected for all patients. Female patients will also provide obstetrical-gynecological anamnesis, while men will provide urological one, if present. Formalin fixed, paraffin embedded diagnostic sample of each patient will be collected and sectioned to obtain: a DNA genomic library to define the mutational profile of a selected panel including 50 tumor-associated genes, a mRNA library to obtain gene expression levels of the corresponding transcripts and protein expression of estrogen receptor Beta (ERß) and DNA repair enzyme ERCC1. Immunohistochemistry reaction, for both ERCC1 and ERβ, will be scored according to the H-score method. NGS analyses will be performed by means of the Ion Torrent Personal Genome Machine (PGM, Life Technologies, Grand Island, NE). Tumor tissues will be tested with commercial library kits: Ion AmpliSeq Cancer Hotspot Panel v.2 to investigate 50 cancer-associated genes and significant gene variations will be further confirmed using Sanger Sequencing method; Ion AmpliSeq™ RNA Cancer Panel to define also gene expression of the same 50 cancer-associated genes (Life Technologies). Correlations among mutational profile, transcriptional pattern, protein levels and clinico-pathological characteristics will be assessed.
Results:
Not Applicable
Conclusion:
Lung cancer incidence in women is increasing worldwide and genetic predisposition, sex hormones or specific molecular features could all account for the clinical differences observed between females and males. Up to the current date, the clinical approach to lung cancer treatment does not rely on gender. The identification of differential status of specific biomarkers can deepen knowledge on the molecular basis of this disease, guiding clinicians towards sex-based treatments.
