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E. Gabrielson
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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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P3.04-050 - Detection of PIK3CA Mutations, including a Novel Mutation of V344G in Exon 4, in Metastatic NSCLC: A Retrospective Study of 139 FNA Cases (ID 957)
09:30 - 09:30 | Author(s): E. Gabrielson
- Abstract
Background:
Several molecular alterations of PIK3CA (phosphatidylinositol-4,5-biphosphate 3-kinases, catalytic subunit alpha) signaling pathways have been detected in primary non-small cell lung carcinoma (NSCLC). These include genomic amplifications of the regulatory subunit p85 and the catalytic subunit p110 alpha, as well as mutations of the helical binding domain on exon 9 and the catalytic subunit on exon 20. A mutation in the PIK3CA gene is a much rarer event than amplification in NSCLCs (approximately 2% in primary NSCLCs). The clinical significance of PIK3CA mutations in carcinoma is still not fully understood and is controversial. For example, some have suggested that PIK3CA mutations are associated with a favorable prognosis in breast cancer, while others have found PIK3CA mutations to be associated with a poor prognosis in primary lung cancers. Additionally, PIK3CA alterations have been associated with EGFR, KRAS and AKT mutations in primary NSCLC. In this study, we have collected FNA specimens of metastatic NSCLCs, investigated PIK3CA mutations, and correlated the findings with other molecular results.
Methods:
We identified 139 fine needle aspiration (FNA) cases of metastatic NSCLC with targeted next-generation sequencing (NGS) analyses of AKT, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes, as well as testing for ALK gene rearrangements by fluorescence in situ hybridization (FISH) at the Johns Hopkins Medical Institute.
Results:
LN: Lymph node; PL: Pleural fluid; PR Peritoneal fluid. (-): not detected.Age Sex Location Diagnosis PIK3CA Mutation (exon #) EGFR Mutation BRAF Mutation KRAS Mutation 63 F LN ADC R88Q (1) (-) V600E (-) 69 M LN ADC V344G(4) E709A (-) (-) G719C 53 F PL ADC V344G(4) T790M (-) (-) E746_A750del 68 M LN NSCLC E542K(9) (-) (-) (-) 58 M PL ADC E542K (9) T790M (-) (-) L747_A750delinsP S768_V769delinsIL (S768I + V769L) 55 F Pelvic Bone SqCC E545K(9) (-) (-) (-) 74 F LN ADC P539R(9) (-) (-) G12C 60 M PR ADC H1047R(20) T790M (-) (-) L858R K860I
Conclusion:
PIK3CA mutation was detected in 5.8% of metastatic NSCLCs. The majority of the mutations were located on exon 9 or exon 20; however, a rare mutation in exon 1 was seen in one case. Further, a novel mutation, to our knowledge, for NSCLC was detected (V344G) in exon 4 in two cases. Among PIK3CA mutations, 50.0%, 12.5%, and 12% were associated with EGFR, BRAF, and KRAS mutations, respectively. In contrast to primary NSCLC, we did not find any metastatic cases to contain both PIK3CA and AKT mutations. The unique role of PIK3CA mutation in metastatic NSCLC and its clinical implications need to be further investigated.
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P3.06 - Poster Session/ Screening and Early Detection (ID 220)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.06-007 - Discovery and Validation of Potential Glycoprotein Biomarkers in the Airway Fluid to Improve the Detection of Lung Cancer from Benign Lung Nodule (ID 925)
09:30 - 09:30 | Author(s): E. Gabrielson
- Abstract
Background:
Recent clinical screening trials using highly sensitive low-dose computed tomography (LDCT) demonstrated an increased detection proportion of stage I lung cancers and improved overall survival of lung cancer patients as the result of early detection. However, lung cancer screening trials also showed high repeat screening rates and false-positive rates causing unnecessary second-line invasive procedures and surgery. New strategies are still needed to improve the specificity of lung cancer screening. The airway fluid, bronchoalveolar lavage (BAL), is commonly used for the evaluation of lung nodules and diagnosis of lung cancers. Proteins in the BAL fluid may serve as potential biomarkers for cancer detection. In this study, we examined the protein profile, particularly the signature of glycoprotein in normal and lung cancer patients.
Methods:
We collected BAL fluid after cellular components were harvested for cytological examination in the cytology laboratory. Protein profile and N-glycoproteins were analyzed using the solid-phase extraction of N-glycoprotein (SPEG) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixteen BAL samples, including four cases each of benign lung disease, adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and small cell carcinoma (SCLC), were analyzed.
Results:
A total of 1013 unique peptides from 457 glycoproteins were identified and quatified. Among them, 286 proteins were identified in BAL of ADC, 363 in squamous cell carcinoma (SqCC), 298 in SCLC and 330 in benign BALs. In addition to common proteins found in all groups, we identified 113 unique proteins that were differentially expresssed in benign disease, ADC, SqCC and SCLC, respectively. The levels of Napsin A, periostin, Galectin-3-binding protein (G3-BP) and myeloperoxidase (MPO) in cancer and benign BALs were further validated using independently collected BAL specimens by ELISA assays (Table 1). Table1. Detection of Proteins in BAL from lung cancer and benign lung disease by ELISA assays.
* protein concentration was expressed as ng/mg total BAL protein. ** for benign lesions.Protein Benign* (n=7) ADC* (n=18) SqCC* (n=9) SCLC* (n=6) Sensitivity (%) Specificity (%) PPV (%) NPV (%) P value Napsin A 55±39 295±104 102±34 50±28 83.3 66.7 88.2 57.1 <0.05 Periostin 255±104 4002±218 3496±1765 1772±1119 73.68 71.43 87.5 50.0 <0.05 G3-BP 168±29 290±70 240±65 132±65 47.4 11.8% 69.2 23.1 >0.05 MPO 3227±2948 0.08±0.03 1.6±0.7 0.1±0.06 33.3 100 100 83.3 <0.05**
Conclusion:
Our study demonstrates that potential protein biomarkers in BAL fluid can be identified and quantified. They have the potential to improve the specificity of lung screening tests and to reduce unnecessary surgery in patients with benign lung nodules.
