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Hans Brunnström
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MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:Yuko Minami, Mary Beth Beasley
- Coordinates: 9/10/2019, 11:30 - 13:00, Tokyo (1982)
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MA18.05 - Diagnostic Difference Between Neuroendocrine Markers in Pulmonary Cancers: A Comprehensive Study and Review of the Literature (Now Available) (ID 171)
11:30 - 13:00 | Presenting Author(s): Hans Brunnström
- Abstract
- Presentation
Background
The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non-small cell carcinomas (NSCC) is of high clinical relevance for prognosis and treatment. Diagnosis is based on morphology and immunohistochemical staining. The current WHO classification of lung tumors emphasizes synaptophysin and chromogranin A but also recommends CD56 as NE markers. The aim of the present study was to determine the diagnostic value of the insulinoma-associated protein 1 (INSM1) gene, in comparison with the established neuroendocrine markers, in pulmonary tumors.
Method
Tissue microarrays with tumor tissue from 54 resected pulmonary NE tumors and 632 NSCC were stained for INSM1, CD56, chromogranin A and synaptophysin. In a subset, gene expression data was available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 37 additional studies with data on NE markers in lung cancers from the last 15 years, whereof six with data on INSM1.
Result
Depending on cut-off level (1%+ or 10%+ positive tumor cells), the sensitivity and specificity for INSM1 to separate NE tumors from NSCC were 72-91% and 98-99%, respectively. In comparison, the sensitivity and specificity for CD56 were 85-89% and 96-98%, for chromogranin A 56-67% and 98-99%, and for synaptophysin 85-93% and 86-92%, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity (see table). INSM1 gene expression was clearly associated with NE histology.
The solid data of our investigation and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 or synaptophysin should be the first-hand choice to confirm high-grade NE pulmonary tumors.
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-37 - Lung Cancer in Never-Smokers: A Nationwide Population Based Mapping of Targetable Alterations (ID 2735)
09:45 - 18:00 | Author(s): Hans Brunnström
- Abstract
Background
Lung cancer among never-smokers is common and increasing [1]. A smoking-independent subgroup of lung adenocarcinoma with certain molecular and clinical features exists [2-3]. In an ongoing project within the Swedish Molecular Initiative against Lung cancer (SMIL) we currently characterize lung cancer in never-smokers for etiological, diagnostic and therapeutic purposes.
Through the Swedish National Lung Cancer Registry [1], we identified all individuals who underwent surgery for lung cancer in Sweden 2005-2014 and who were registered as never-smokers (n=540). At each study site, clinical data were reviewed by a thoracic oncologist or pulmonologist through patients’ medical charts and archived tumor tissues were retrieved and reviewed by a thoracic pathologist. For subsequent studies, we extracted DNA and RNA (using the Qiagen AllPrep kit for FFPE tissue) and constructed tissue microarrays. As first preplanned analyses, we performed fusion gene mapping using an RNA based NanoString nCounter Elements assay and mutational profiling by Next Generation Sequencing (NGS) using a 26-gene exon-focused panel, as previously described [4].
Of the 540 never-smokers with surgically resected lung cancer, 69% were females and the majority of cases were adenocarcinomas. The median age at diagnosis was 69 years.
In the first 310 analyzed tumor samples, we so far detected 24 fusions involving ALK (8%), 10 involving RET (3%) and 2 involving NRG1 (<1%). In addition, MET exon 14 skipping was found in 33 samples (11%).
Furthermore, among the so far 147 cases where we have completed both the DNA and the RNA analyses, 59 tumors (40%) harbored EGFR mutations. In total, targetable alterations were revealed either by NanoString or NGS in 63% of tumors from never-smokers in our study.
SMIL is an ongoing nation-wide molecular research collaboration on lung cancer where we currently characterize one of the largest never-smoking lung tumor cohorts worldwide. From the first pre-planned analyses, we conclude that, in a population-based cohort of early stage lung cancer from never-smokers, targetable oncogenic fusions and mutations are frequent.
References
1. http://www.cancercentrum.se/vast/cancerdiagnoser/lunga-och-lungsack/kvalitetsregister
2. Staaf J, Jönsson G, Jönsson M, Karlsson A, Isaksson S, Salomonsson A,Pettersson HM, Soller M, Ewers SB, Johansson L, Jönsson P, Planck M. Relation between smoking history and gene expression profiles in lung adenocarcinomas. BMC Med Genomics. 2012 Jun 7;5:22.
3. Karlsson A, Ringnér M, Lauss M, Botling J, Micke P, Planck M, Staaf J. Genomic and transcriptional alterations in lung adenocarcinoma in relation to smoking history. Clin Cancer Res. 2014 Sep 15;20(18):4912-24.
4. Lindquist KE, Karlsson A, Levéen P, Brunnström H, Reuterswärd C, Holm K, Jönsson M, Annersten K, Rosengren F, Jirström K, Kosieradzki J, Ek L, Borg Å, Planck M, Jönsson G, Staaf J. Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer. Oncotarget. 2017 May 23;8(21):34796-34810.