1. LAUREN POLLI
P a th o l o g i s ts ’ A s s i s ta n t S tu d e n t
D r e x e l Un i v e r s i ty
M S P A 5 4 1 S H i s to te c h n o l o g y I I
Tu e s d a y , A p r i l 1 7 , 2 0 1 2
Non Small Cell Lung Cancer &
Treatment Breakthroughs
3. Patient History
41 year old female
History of adenocarcinoma of the lung
No other history given
Smoker? Secondhand smoke?
Chemical Exposure?
Genetic Disposition?
5. Adenocarcinoma
Malignant epithelial
tumor with glandular
differentiation or mucin
production by the tumor
cells
Robbins & Cotran
Patterns
Acinar
Papillary
Bronchioloalverolar
Solid with Mucin Formation
Males 37%, Females 47%
Significantly increased in
the last two decades
Most common type of
lung cancer in women &
non smokers
Grow more slowly but
tend to metastasize
widely & earlier
6. Differential Diagnosis
Biopsy
H & E
Small Cell
Carcinoma
IHC; Target Now?
Non-Small Cell
Carcinoma
Squamous Cell
Carcinoma
Target Now?
Adenocarcinoma
Molecular
Poorly
Differentiated
IHC
7. Gross Description
CT Guided Biopsy
Lung: Right Lower Lobe
Also received in formalin in a container are 3 white
tan tissue cores measuring 0.6 cm, 0.7 cm, 0.8 cm,
0.9 cm, and 1.4 cm in length and 0.1 cm in
diameter. The container is labeled with patient’s
name, date of birth and/or medical record
number, and designated “RLL Lung Bx”. The
specimen is submitted entirely in 3 cassettes for
permanent histologic examination. Cassettes
designated:
A1 one core
A2 two cores
A3 two cores
15. Molecular Testing
Drexel University
Molecular Diagnostic
Laboratory
Take tissue directly
from paraffin block
All assays are PCR
based
Determine sensitivity or
resistance of tumor to
therapeutic
intervention
Mutations Tested
o EGFR
o KRAS
o BRAF
16. EGFR
Epidermal Growth Factor Receptor
Test ordered when NSCLC are WT for KRAS
Adenocarcinomas
Multiple mutations with clinical ramifications
Sensitive or resistant to tyrosine kinase inhibitor therapy
Patient Results
No EGFR Mutation
17. KRAS
Proto-oncogene in the EGFR pathway
Mutations disrupt an inhibitory domain resulting
in constitutive activation of its tyrosine kinase
domain
Mutations are resistant to anti EGFR therapy
Negative results lead to BRAF testing
Patient Results
No KRAS Mutation
18. BRAF
Serine threonine kinase in EGFR pathway
Activates pathway leading cells to proliferation,
differentiation, migration/motility, adhesion,
protection from apoptosis, enhanced survival,
gene transcription
Mutation leads to constitutive activation
Patient Results
No BRAF Mutation
19. ALK Fluorescence In Situ Hybridization
3-5% of NSCLC have a
rearrangement of ALK
gene
Fusion between ALK &
another gene ALK
activation impaired
apoptosis abnormal
cell proliferation
Tumors with
rearrangement
respond to ALK kinase
inhibitors
Detects all potential
fusion rearrangements
20 known
rearrangements
NeoGenomics
http://www.neogenomics.com/alk-rearrangement-in-nsclc.htm
20. ELM4-ALK FISH
•Dual color break
apart probe to
detect gene
rearrangement
•Most Common=
1R1G1F
•Patient’s Results
• 1R1G1F 17%
• 2R1G1F 38.5%
•Quality Control -Results: Abnormal
21. Target Now
Molecular profiling to determine biomarkers of
tumors
Provides individualized therapy regimen and
information on effectiveness of therapy
Shows treatment alternatives when standard of
care has been exhausted in highly aggressive or
rare tumors
Agents Associated with Clinical Benefit
Fluorouracil