Current Concepts in the Diagnosis of Lung Cancer
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Current Concepts in the Diagnosis of Lung Cancers
BY THEINTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER
ADELAIDE CONVENTION CENTERADELAIDE, SOUTH AUSTRALIA, AUSTRALIA
FELIPE S TEMPLO JR., MD
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PART I: ANATOMICAL PATHOLOGY NEEDS
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PHC data (1998-2003). Templo FS, Orillaza MA, Tan CD (2003)
Correct specific diagnosis in 30% (38% SCC and 23% AdenoCA)
NSCLC-NOS is 62% (22.6% SCC and 37.7% AdenoCa)
Incorrect specific diagnosis is 7.5% (10% AdenoCA and 4.7% SCC)
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LEPIDIC
ACINAR
PAPILLARY MICROPAPILLARY
SOLID WITH MUCIN
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PART II: MOLECULAR PATHOLOGY NEEDS
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Testing for research purposes only
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MUTATION TESTING
EGFR :exons 19 &21; exons 18-21KRAS :(exon 2/codon12-13(OPTIONAL)
FISHALK
NO TESTINGUNLESS REQUESTEDBY THE ONCOLOGIST
2010
SQUAMOUS CELL CANON-SQUAMOUS CELL CA*
NON-SMALL CELL LUNG CARCINOMAS
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22012
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5 unstained sections
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5 unstained slides
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KRAS MUTATION TESTING
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EML-4-ALK TESTING
Positive fortranslocation
Negative fortranslocation
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Laser microdissection
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GENERAL RECOMMENDATIONS FOR EGFR/KRAS TESTING:
Blocks (formalin-fixed, paraffin-embedded) are highly recommended for optimal testing.
Testing can be performed on primary tumor or a site of metastasis1) FFPE tissue block containing 20% to 25% tumor OR2) 3-4 precut unstained slides from paraffin block in 5 micron sections and one H&E reference slide (manual microdissection)
Use special slides for laser microdissection (7 micron) FFPE blocks from surgical resections, excisional biopsies, fine
needle aspirates (FNA) and biopsy, core needle biopsies, cell blocks (pleural effusions, ascites and FNAs) and bone marrow.
A minimum of 300-500 viable tumor cells are required.
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EXPERIENCE AT ST VINCENT’S HOSPITAL
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TISSUE COLLECTION/FIXATION
FIXATION/TISSUE PROCESSING
PATHOLOGIST’S REVIEW AND REPORT
DECISION FOR EGFR MUTATION ANALYSIS, TUMOR CONTENT REVIEWED
TUMOR MICRODISSECTION IF NEEDED
EGFR MUTATION TESTING
FINAL REPORT WITH TUMOR HISTOLOGY AND MUTATION RESULTS
24 HOURS
1-2 WORKINGDAYSEXCEPT IHC
5-7 WORKING DAYS
BIOPSY
PATHOLOGY
MOLECULARTESTING
FINALREPORT
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NEW CANDIDATE PREDICTIVE MARKERS
HER2 RAF PI3KCA–AKT–mTOR pathway C-MET Insulin-like growth factor (IGF1R) Fibroblastic growth factor receptor 1 (FGFR1) and
discoidin domain receptor family, member 2 (DDR2) Target molecules for chemotherapeutic agents
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Questions?
1. Which Patients Should Be Tested for the Presence of These Mutations to Determine Their First-line Therapy Options?
First, what is the chance of an activating mutation being present?
Second, what is the cost of testing? How should testing be performed?
Which mutations of the EGFR are clinically significant?2011 by American Society of Clinical
Oncology.
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Questions?2. Should Patients with Less than 10 Packs/Year
Smoking History and Non-squamous Histology Be Empirically Treated with Oral EGFR TKIs
in the Absence of EGFR Testing?
3. Should KRAS Testing Be Used to Deny Patients Therapy with Oral EGFR TKI Inhibitors?
4. Is There a Role for EGFR FISH Testing When Considering the Use of First-generation Oral EGFR TKIs? 2011 by American Society of Clinical Oncology.
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Questions?
5. How Common Is ALK?
6. What Are the Key Clinical Features Associated with ALK?
7. Should All Patients with NSCLC Be Tested for ALK?
2011 by American Society of Clinical Oncology
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Questions?
8. Should Patients with EGFR or KRAS Mutant Lung Cancer be Tested for ALK?
9. What Is the Diagnostic Test of Choice for ALK?
10. Are There Other Diagnostic Modalities for ALK?
2011 by American Society of Clinical Oncology
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Copyright © 2012 by the International Association for the Study of Lung Cancer
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ACKNOWLEDGEMENT1. DR. LINDY CLARKE, FRCPA The Prince Charles Hospital
Brisbane, Queensland, Australia
2. DR. PRUDENCE RUSSELL, FRCPA St. Vincent’s Hospital and Peter McCallum Cancer Centre Melbourne, Victoria, Australia
3. Ms. KAREN LATHER The Australian Lung Foundation
Adelaide, South Australia, Australia
Copyright © 2012 by the International Association for the Study of Lung Cancer