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Tabatha Gutierrez Prieto
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P36 - Pathology - Prognosis (ID 106)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P36.07 - Pleckstrin Homology-Like (PHLDA) Domain Family Members Immunoexpression as Prognostic Marker in Lung Cancer and Mesothelioma (ID 1444)
00:00 - 00:00 | Author(s): Tabatha Gutierrez Prieto
- Abstract
Introduction
Pleckstrin Homology-like Domain, Family A is evolutionary conserved and comprises three members that are located on different chromosomes: PHLDA1 (12q21.2), PHLDA2 (11p15.4) and PHLDA3 (1q32.1). Altered expression of these genes has been described in different types of tumors. All three members, PHLDA1, 2, and 3 acts as AKT inhibitors through the depletion of membrane-bound phosphatidyl inositols. In previous studies, we consistently found PHLDA expression as a predictor of poor prognosis for breast cancer. Here we hypothesize that PHLDA protein evaluation in lung cancer and mesothelioma might define novel predictors of prognosis and therapeutic strategies for these patients. Thus, we evaluated PHLDA1, PHLDA2, and PHILDA3 expression in non-small cell lung carcinoma (NSCLC) and malignant mesothelioma (MM). Breast carcinoma (BC) samples were used as control for the IHC reactions.
Methods
Immunohistochemical analysis was performed on tissue microarrays containing 102 primary tumors (MM, N=61, NSCLC, N = 41) from patients with stage I–IIIA and were examined by image analysis using the software QuPath (Figure 1) to evaluate the expression of PHLDA1, PHLDA2, and PHLDA3. Cell phenotype data were then integrated with clinicopathologic characteristics and the status of p53 protein expression.
Results
The clinicopathological characteristics of patients with NSCLC and MM are shown in Table 1. We found significant association between high expression of PHLDA1 and PHLDA2 protein with p53 protein (p=0.03; p=0.01; respectively). In contrast, low expression of PHLDA3 protein was significant associated with MM (p=0.001), IIIB tumor stage (p=0.001) and low p53 protein expression (p=0.008). Multivariate analysis by Cox Regression controlled for gender, age, tumor groups and p53 protein expression showed significant risk of death for male patients (OR=1.66) with MM (OR=1.20) and low expression of PHLDA3 (OR=1.03).
Conclusion
PHLDA1, PHLDA2, and PHLDA3 co-expression and its relationship with p53 protein expression may better predict patient outcome and response to target therapy.
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P47 - Small Cell Lung Cancer/NET - Biology / Translational (ID 234)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P47.11 - DLL-3 and ASCL-1 Expression Emerge as Promising Therapeutic Targets in High-Grade Neuroendocrine Lung Tumors: A Preliminary Study (ID 1291)
00:00 - 00:00 | Presenting Author(s): Tabatha Gutierrez Prieto
- Abstract
Introduction
Small cell lung carcinoma (SCLC) comprise approximately 13% of the all primary lung tumors and has a very aggressive behavior, often presents metastatic at the time of diagnosis, and therapeutic surgical resection is rarely considered. DLL-3 (Delta-like protein 3) is a Notch ligand and transcriptional target of ASCL-1 (Achaete-scute homolog-1) that has crucial role in the tumorigenesis of SCLC. The correlation between DLL-3 and ASCL-1 expression in high-grade neuroendocrine lung tumors (SCLC and LCNEC) may be provide a target in immunotherapy for the patients.
Methods
Design. We analyze 28 samples that were obtained by archival formalin-fixed paraffin-embedded histological sections (SCLC, N=22; LCNEC, N=6) from patients who underwent surgical resection. Image analysis-based assessment of immunohistochemistry ASCL-1 and DLL-3 protein levels were performed and the clinicopathological features of patients were correlated. Brownish cytoplasmic staining in tumor cells were considered evidence of antigen expression and evaluated as positive (Figure 1).
Results
The clinicopathologic characteristics of patients stratified among the histological subtype are shown in Table 1. ASCL-1 immunohistochemical staining was positive for all patients (N=28), whereas in DLL-3, positive staining was observed in 21 samples (75%), however the high expression was observed in 14 samples (50%) for both. Multivariate analysis by Cox regression showed that older patients, smokers, without radiotherapy, SCLC, low ASCL-1 and DLL-3 expression, presented high risk of death (OR=3.79; p=0.05).
Conclusion
ASCL-1 and DLL-3 were highly expressed in patients diagnosed with neuroendocrine lung tumor. Despite the small sample size, this is a preliminary study, our data are similar to literature. Our results may support that DLL-3 and ASCL-1 may be provide a promise targets for immunotherapy in neuroendocrine lung tumors.
