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A. Aviles-Salas
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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: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-020 - ALK Rearrangements Epidemiology in Latin America (CLICaP) (ID 2957)
09:30 - 09:30 | Author(s): A. Aviles-Salas
- Abstract
Background:
Latin American countries are heterogeneous in terms of lung cancer incidence, ethnicity, and exposure to potential carcinogens. The discovery of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation as an oncogenic driver has led to the development of novel therapies with activity in vitro and in the clinic. In this study we evaluated the frequency and clinical characteristics of ALK rearrangements in six Latin-American countries.
Methods:
A total of 2799 biopsies of advanced NSCLC patients from 6 countries of Latin America (Argentina, Colombia, Costa Rica, Panama, Ecuador, and Mexico) were evaluated by the method fluorescence in situ hybridization (FISH) for detection of ALK-rearrangements. Demographic and clinicopathologic characteristics were analyzed.
Results:
The FISH analyses showed positive ALK fusion gene status in 6.55% (181/2761) of the total sample from all participating countries. ALK+ for each country was a follows: Argentina 6.08% (105/1726), Colombia 4.83% (10/207), Costa Rica 4.83% (2/49), Mexico 8.57% (64/746), and Panama 0% (0/33). Ecuador only used immunohistochemistry for ALK detection rearrangement; therefore, these samples were excluded from FISH technique analysis.
Conclusion:
The frequency of ALK rearrangement in Latin America is higher than previously reported for the Caucasian and Japanese populations. In addition, there is significant continental variability. Until now, FISH for ALK testing is not widely available in Latin America due to its high cost, time-consumption and result interpretation. There is an increased need to develop a common platform for genomic evaluation in developing countries.
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P3.04-090 - Association of Nuclear Expression of RAR Beta and YY1 with Prognosis in Advance Non-Small Cell Lung Cancer (ID 1697)
09:30 - 09:30 | Author(s): A. Aviles-Salas
- Abstract
Background:
Lung cancer is the most common cause of cancer-related death worldwide and it is responsible for approximately 1.4 million deceases per year. In Mexico, the NSCLC cause more than 6,697 deaths annually. Approximately, 85% of all lung cancer corresponds to NSCLC and unfortunately at diagnosis 60% patients have advanced unresectable disease with a very poor prognosis. The standard of care treatment for advanced disease is platinum-based doublet chemotherapy, this present an objective response rates of 19% to 37% with a 7 to 10 months of median survival. The identification of molecular alteration in NSCLC has transformed the clinical management of this disease, increasing the survival and improves the response in patients. The genetic alterations affect a common group of oncogenic signaling pathways such as retinoid receptors (RR) and yin and yang 1 (YY1) resulting in lung cancer development and progression. The nuclear RR may play a critical role in the process of lung carcinogenesis. In NSCLC, reduction in the levels of mRNA RARβ and RARα have associated with lack of response to treatment and progression. As the same manner, YY1 is a key regulator of multiple signaling pathways involved in differentiation, replication, cellular proliferation and oncogenic transformation. The role of YY1 in development of cancer depend upon the context in which it binds. It could activate a variety of oncoproteins attenuates the stability of the tumor suppressor such as p53 or mediates the activation of genes with tumor-suppressive functions. The aim of this study was to analyze the expression of RARα, RARβ and YY1 and its relationship with overall survival in patients with advanced NSCLC.
Methods:
This was an observational study, where patients with advanced NSCLC at the National Cancer Institute of Mexico City from July 2005 to December 2011 were enrolled. The expression of RARα, RARβ and YY1, was determinate with immunohistochemistry by mean digital pathology and analyzed by Image-Pro Plus.
Results:
Eighty-five patients were included for the analysis. The mean and standard deviation of the nuclei expression of RARα, RARβ and YY1 were (106.7±97), (14±13) and (13±12). Patients with a high RARβ total expression have a better ECOG 0-1 vs 2-3 performance status (92.9 vs 74.4%). Non-smokers had a high nuclei expression of YY1 (61.9 vs <40.5%) and better median OS 15.6 (4.5-26.7 months). Nuclei expression of RAR-β was associated with the nuclei expression of YY-1 (R2 = 0.28; p-Value <0.0001). Also, the higher nuclei expression of RARβ was associated with a higher OS (27.5 vs 8.7 months) in both, the univariate analysis and multivariate analysis (p=0.016; p=0.037).
Conclusion:
The nuclei expression of both RARβ and YY1, could be used as biomarkers to NSCLC prognosis, specifically YY1 predicted a better response in patient that had never smoke.
