1. Current Concepts
in the Diagnosis of Lung Cancers
BY THE
INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER
ADELAIDE CONVENTION CENTER
ADELAIDE, SOUTH AUSTRALIA, AUSTRALIA
FELIPE S TEMPLO JR., MD

2. PART I: ANATOMICAL PATHOLOGY
NEEDS

22. 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)

39. LEPIDIC
ACINAR
PAPILLARY MICROPAPILLARY
SOLID WITH MUCIN

45. PART II: MOLECULAR PATHOLOGY
NEEDS

47. Testing for research purposes only

48. 2010
NON-SMALL CELL LUNG CARCINOMAS
NON-SQUAMOUS CELL CA*
SQUAMOUS CELL CA
MUTATION TESTING
EGFR :exons 19 &21;
NO TESTING
exons 18-21
UNLESS REQUESTED FISH KRAS :(exon 2/codon12-13
BY THE ONCOLOGIST ALK (OPTIONAL)

49. 22012

50. 5 unstained sections

52. 5 unstained slides

53. KRAS MUTATION TESTING

55. EML-4-ALK TESTING
Positive for
translocation
Negative for
translocation

57. Laser microdissection

58. 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
metastasis
1) FFPE tissue block containing 20% to 25% tumor OR
2) 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.

60. EXPERIENCE AT ST VINCENT’S HOSPITAL

61. TISSUE COLLECTION/FIXATION
24 HOURS BIOPSY
FIXATION/TISSUE PROCESSING
PATHOLOGIST’S REVIEW AND
1-2 REPORT PATHOLOGY
WORKING
DAYS
EXCEPT DECISION FOR EGFR MUTATION ANALYSIS,
IHC TUMOR CONTENT REVIEWED
TUMOR MICRODISSECTION IF NEEDED MOLECULAR
TESTING
5-7
WORKING EGFR MUTATION TESTING
DAYS
FINAL
FINAL REPORT WITH TUMOR HISTOLOGY REPORT
AND MUTATION RESULTS

63. 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

65. 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.

66. 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.

67. 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

68. 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

69. Copyright © 2012 by the
International Association for the Study
of Lung Cancer

70. ACKNOWLEDGEMENT
1. 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