![Page 1: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/1.jpg)
Molecular Diagnostic Tests in Respiratory Tract Cytology:
Experiences in Taiwan
Chih-Yi Liu MD, FIAC
Division of Pathology, Sijhih Cathay General Hospital,
New Taipei City, Taiwan
Conflict of interest: no disclosure
![Page 2: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/2.jpg)
Outlines Personalized medicine and molecular diagnostic tests
Molecular profile of lung cancer
Lung cancer statistics and molecular tests in Taiwan
Current guidelines and trends in specimen management
Cytology in precision medicine
![Page 3: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/3.jpg)
Personalized Medicine is a Multi-Faceted Approach to Patient Care
Risk Assessment: Genetic testing to reveal predisposition to disease
Prevention: Behavior/Lifestyle/Treatment intervention to prevent
disease Detection: Early detection of disease at the molecular level
Diagnosis: Accurate disease diagnosis enabling individualized
treatment strategy
![Page 4: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/4.jpg)
Personalized Medicine is a Multi-Faceted Approach to Patient Care
Treatment: Improved outcomes through targeted
treatments and reduced side effects Management: Active monitoring of treatment response and
disease progression
![Page 5: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/5.jpg)
![Page 6: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/6.jpg)
![Page 7: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/7.jpg)
Lung Cancer Statistics in Taiwan 2015
![Page 8: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/8.jpg)
Lung Cancer Statistics in Taiwan 2015
![Page 9: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/9.jpg)
Lung Cancer Statistics in Taiwan Molecular Profile
![Page 10: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/10.jpg)
Molecular Tests in Taiwan
![Page 11: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/11.jpg)
Molecular Tests in Taiwan
EGFR and ALK testing in patients with (1) Adenocarcinoma (2) Carcinoma with adenocarcinoma component (3) Non-small cell carcinoma, NOS (4) Squamous or small cell carcinoma diagnosed in
biopsy specimen in non-smoking patient
Acceptable sample types: – Primary tumor / Metastasis – Histological samples / Cytological samples – Liquid biopsy
![Page 12: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/12.jpg)
Molecular Tests in Taiwan
EGFR testing method requirement: – Validated methods with proper test performance – Sensitivity: at least 25% mutated allele frequency – Can detect L858R, exon 19 deletions and T790M
ALK testing method recommended: – Dual-labeled break-apart FISH – Specific amplified immunohistochemistry
![Page 13: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/13.jpg)
Tests for Immunotherapy
Programmed death receptor-1 (PD-1) is expressed by T-cells Programmed death ligand-1 (PD-L1) is the ligand for PD-1 : Binding of PD-1 to PD-L1 on tumor cell can diminish the function of the T-cells Drugs developed to disrupt this interaction
• Antibodies target PD-1 • Second-line therapies
Progression following platinum chemotherapy or EGFR/ALK-targeted therapy
https://pbs.twimg.com/media/CmMCAJzUsAACFDM.jpg
![Page 14: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/14.jpg)
Use Test Specimens from Minimally Invasive Procedures: Doing More With Less
Slide modified from Dr. Andre Moreira and Anjali Saqi, ascp.org/2016
![Page 15: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/15.jpg)
Substrates for Molecular Testing
Histology specimens Cytology specimens Cell blocks Prepared slides (direct or imprint smears,
cytospin, LBC smears; cell transfer and scraping)
Residual fixed sample (LBC) Fresh sample
![Page 16: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/16.jpg)
Specimen Preparation and Testing on Cytology
Slide modified from Dr. Natasha Rekhtman
![Page 17: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/17.jpg)
Specimen Preparation and Testing on Cytology
Roy-Chowdhuri S, Stewart J. Preanalytic Variables in Cytology: Lessons Learned From Next-Generation Sequencing-The MD Anderson Experience. Arch Pathol Lab Med. 2016 Jun 22.
![Page 18: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/18.jpg)
National Comprehensive Cancer Network Clinical Guideline
Important points for cytology If limited disease- Surgery If metastatic, need molecular testing Most metastatic disease will be diagnosed
by cytology Obtain sufficient material for molecular testing:
EGFR, ALK- must Other testing may be considered
ROS, KRAS, BRAF, RET, ERBB2 (HER2), PIK3CA, MET, PD-L1, MGMT
![Page 19: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/19.jpg)
![Page 20: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/20.jpg)
How to Enrich Cell Content
Cytolyt solution/Cytorich Red solution Slide enrichment - Laser capture microdissection - Direct microdissection - Cell transfer
![Page 21: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/21.jpg)
45 y/o female, nonsmoker, came to Orthopedics due to intermittent right hip pain for several months.
Imaging study revealed a pelvic mass suggesting malignancy
Example
Courtesy of Dr. Chiung-Ru Lai, TVGH, Taiwan
![Page 22: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/22.jpg)
Bone biopsy: adenoca, TTF1+ Final diagnosis: lung adeno, RUL, cT2aN2M1b with bone, brain and adrenal metastases
![Page 23: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/23.jpg)
EGFR mutation testing
Block number: S104-37042 Percentage of tumor cells in selected region for DNA extraction: 40% Amount of viable tissue submitted: 2 mm x 2 mm x 12 um
![Page 24: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/24.jpg)
FNA of bone lesion Direct smears and LBC
![Page 25: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/25.jpg)
EGFR mutation testing
No more pain killer after one-week of EGFR-TKI treatment
Cytospin from residual material of FNA LBC specimen Percentage of tumor cells in selected region for DNA extraction: 80%
![Page 26: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/26.jpg)
Challenges to the Cytopathologists
Malignancy YES/NO
SCLC vs. NSCLC
Primary vs. Metastasis
NSCLC subtype
Predictive markers
![Page 27: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/27.jpg)
Conclusions
The role of the cytopathologists/cytotechnologists in molecular testing: be the bridge between the clinical team and the molecular lab Provide the best material for molecular testing
Know your test. Know your limitations. Modulate the platform for the specimen (high analytic
sensitivity) Know your specimen Modulate the specimen for the platform (tumor
enrichment) Know your clinical team Prioritize testing to answer clinically relevant questions
![Page 28: Molecular Diagnostic Tests in Respiratory Tract Cytology ......Molecular Diagnostic Tests in Respiratory Tract Cytology: Experiences in Taiwan Chih-Yi Liu MD, FIAC Division of Pathology,](https://reader034.vdocument.in/reader034/viewer/2022052105/6040a96e2854010c177bce4c/html5/thumbnails/28.jpg)