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G. Alì
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-077 - Whole-Transcriptome Gene Expression Analysis of Pulmonary Sarcomatoid Carcinomas (ID 5477)
14:30 - 14:30 | Author(s): G. Alì
- Abstract
Background:
Pulmonary sarcomatoid carcinomas (PSCs) are rare, poorly differentiated non-small cell lung cancers (NSCLCs) containing sarcoma or sarcoma-like features, with a worse prognosis than other NSCLCs. The World Health Organization (WHO) classifies three histopathologic subtypes: subtype-1 includes pleomorphic, spindle-cell, and giant-cell carcinomas (PSCGC), subtype-2 carcinosarcoma and subtype-3 blastoma. The value of different subtypes for clinical management and their molecular characteristics are unclear. The aim of this study is to get new insights into PSCs carcinogenesis by a high-throughput sequencing of RNA (RNA-seq).
Methods:
A whole-transcriptome targeted-gene quantification analysis was retrospectively performed on RNA from formalin-fixed paraffin-embedded tissues of 13 PSCs (5 pleomorphic, 2 spindle-cell, 2 giant-cell carcinomas, 4 carcinosarcomas). RNA-seq reads were mapped to the amplicon sequences of the panel and quantified by tools based on alignment algorithms. Differentially expressed genes between subtype-1and -2 were determined using a non-parametric Mann-Whitney U-test (p-value < 0.01) with linearity correction. Moreover, within subtype-1 we compared gene expression levels between monophasic (spindle- and giant-cell) and biphasic (pleomorphic) carcinomas.
Results:
216 genes resulted down-regulated and 15 up-regulated in PSCGC compared to carcinosarcomas (Table 1). There were not significant differences between monophasic and biphasic PSCGC. Figure 1
Conclusion:
PSCs are heterogeneous tumours, barely characterized from a molecular point of view. WHO has recently classified PSCGC and carcinosarcoma as two distinct entities, and our results demonstrated that they effectively have different gene expression profiles. Deregulated genes mostly belong to pathways crucial for cancer, like p53-, MAPK- and Wnt-signaling, and future investigation should clarify their specific role in PSCs. Interestingly, we did not find statistically deregulated genes among monophasic and biphasic carcinomas of subtype-1, thus indicating their molecular similarity. Although this is a preliminary and explorative study, needing further validation, it constitutes a starting point to increase our knowledge of these rare tumours.
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P3.02a - Poster Session with Presenters Present (ID 470)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02a-010 - Evaluation of Aberrant ALK Expression in Lung Cancer by RT-PCR and Comparison with FISH and Immunohistochemistry (ID 5490)
14:30 - 14:30 | Author(s): G. Alì
- Abstract
Background:
In advanced lung cancer patients the gold standard for detecting ALK gene rearrangements is fluorescence in situ hybridization (FISH), and ALK protein expression can be also evaluated by immunohistochemistry (IHC). A single analysis performed alone may not detect all the ALK-positive cases and some patients with discordant FISH and IHC respond to tyrosine kinase inhibitors (TKIs). In this study we evaluated ALK aberrant expression in lung cancer patients by a reverse-transcription (RT)-PCR, to investigate its clinical utility and its concordance with FISH and IHC.
Methods:
ALK aberrant expression was retrospectively investigated on RNA from formalin-fixed paraffin-embedded tissue (FFPEt) of 24 advanced lung adenocarcinoma patients, previously evaluated by FISH and IHC. We used a one-step Scorpion RT-PCR that allowed in a single reaction either the mRNA reverse transcription and the cDNA amplification for ALK kinase-domain, normally not expressed, and a control gene, to assess RNA quality.
Results:
Results are reported in Table 1.Figure 1
Conclusion:
Despite the instability of mRNA from FFPEt, only 2 samples resulted inadequate for RT-PCR. RT-PCR was in disagreement with both FISH and IHC in one case, which is likely to be a RT-PCR false positive. RT-PCR did not detect ALK aberrant expression in a FISH positive case, which was negative also by IHC; unfortunately, this patient died after a cycle of pemetrexed therapy, before undergoing a second line TKI treatment. The presence of ALK rearrangements does not necessarily imply increased protein levels, because of the complex transcriptional and post-transcriptional regulations, so further analysis at RNA levels may clarify discrepancy between FISH and IHC allowing a better stratification of patients who could benefit from TKIs. Therefore, according to our results the RT-PCR evaluating ALK aberrant expression regardless of the fusion partners should be considered for introduction into routine ALK testing in lung cancer.
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-024 - Malignant Pleural Mesothelioma: Gene Expression Profiling of the Main Histological Subtypes (ID 5465)
14:30 - 14:30 | Author(s): G. Alì
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is a low-incidence, aggressive, asbestos-related tumor, whose treatment options are currently limited. MPM is a heterogeneous tumor with three main histological subtypes: epithelioid (E), sarcomatoid (S) and biphasic (B). S- and B- MPMs are rarer and have a poorer prognosis than the E-subtype. In the present study we compared the expression profile of 117 genes with a crucial role in cancer between the E- and S/B- subtypes, in order to identify histology-specific molecular markers.
Methods:
Gene expression analysis was performed by Nanostring system directly on RNA from 38 formalin-fixed and paraffin-embedded tissues of MPM patients (25 E-subtype, 13 S/B-subtypes). After data normalization, differences of gene expression levels between the two groups were evaluated by a non-parametric Mann-Whitney U-test (p-value < 0.05).
Results:
39 genes were differentially expressed. In particular, 21 genes were statistically up-regulated and 18 down-regulated in E- compared to S/B-subtypes (Table 1). Figure 1
Conclusion:
The identification of gene expression profiles specific for each histological subtype could improve the clinical approach to MPM. In this study we found genes differentially expressed between E- and S/B-subtypes. In detail, up-regulated genes in E-MPM encode for proteins involved in epithelial cell differentiation and regulation of apoptosis, whereas down-regulated genes belong to pathways related to extracellular matrix, cell adhesion and angiogenesis. Moreover, some of the deregulated genes have been already described to influence the sensitivity to chemotherapy, such as ASS1, to play an important role in the mesenchymal transition, like MMP9, and others, among which ESR2, have been proposed as potential therapeutic targets. Our results reveal genes activated or inactivated in a histotype-dependent manner as new potential biomarkers for MPM, however, further studies are needed to better understand their clinical value.
