Molecular Diagnosis of Lung CancerMolecular Diagnosis of Lung Cancer A. John Iafrate, MD, PhD ... DNA mutations DNA chromosomal alterations mRNA and miRNA profiling Proteomics

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Molecular Diagnosis of Lung Cancer A. John Iafrate, MD, PhD

February 21, 2012

Hot Topics in

Pathology Series

• Director of Molecular

Pathology at Massachusetts

General Hospital

• Associate Professor in

Pathology at Harvard Medical School

• He specializes in adult

medicine especially anatomic and molecular

genetic pathology

• His research interest has

focused on the overall

genetic link to lung cancer

A. John Iafrate, MD, PhD

© 2011 College of American Pathologists. All rights reserved. 2

• The College does not permit reproduction of any substantial portion of the material in this Webinar without its written

authorization. The College hereby authorizes attendees of the

CAP Webinar to use the pdf presentation solely for educational

purposes within their own institutions. The College prohibits use of the material in the Webinar – and any unauthorized use of

the College’s name or logo – in connection with promotional

efforts by marketers of laboratory equipment, reagents,

materials, or services.

• Opinions expressed by the speaker are the speaker’s own and

do not necessarily reflect an endorsement by CAP of any

organizations, equipment, reagents, materials or services used

by participating laboratories.

Disclaimer


• Paid consultant for Pfizer

• Paid consultant for Abbott Molecular

• Paid consultant for BioReference Laboratories

Disclosure


Haber, Gray, Baselga Cell 2011

A New Paradigm in Cancer Treatment

BCR-ABL Imatinib

100% CML HER2 Trastuzumab

20-30% IDC

EGFR Erlotinib/ Gefitinib

20% Lung adenocarcinomas

ALK Crizotinib

3-5% Lung

adenocarcinoma

BRAF V600E PLX4032 50-60% Melanoma

BRAF

1799 T>A

V600E

BCR-ABL Imatinib

100% CML HER2 Tastuzumab

20-30% IDC

EGFR Erlotinib/ Gefitinib

20% Lung adenocarcinomas

ALK Crizotinib

3-5% Lung

adenocarcinoma

BRAF V600E PLX4032 60% Melanoma

BRAF

1799 T>A

V600E

Romond EH et al., Trastuzumab

plus Adjuvant Chemotherapy for

Operable HER2-Positive Breast

Cancer. NEJM 2005.

O’Brien et al., Imatinib Compared with Inter-

feron and Low-Dose Cytarabine for Newly

Diagnosed Chronic-Phase Chronic Myeloid

Leukemia, NEJM 2003

Mok et al., NEJM 2009

Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines(r)) for Non-Small Cell

Lung Cancer V.3.2012. (c) 2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines(r)

and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the

NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NATIONAL

COMPREHENSIVE CANCER NETWORK(r), NCCN(r), NCCN GUIDELINES(r), and all other NCCN Content are trademarks owned by

the National Comprehensive Cancer Network, Inc.

MGH Translational Research Laboratory

Cancer Patients

Oncology Clinical trials

Improved Clinical Use of Genotyping

Basic Research

Centers

MGH Pathology

Specimen Repository

Genotyping

• Real-time screening of

patient tumor samples for

genetic alterations.

• Employing high-throughput

genotyping technologies.

(>100 samples/week)

• Directing patient therapy

based on genetic

fingerprint.

Prospective

Enrollment

Clinical Genotyping in Guiding Therapeutic Decisions

Comprehensive Genetic Characterization of Tumors

for Personalized Cancer Care

DNA mutations

DNA chromosomal

alterations

mRNA and miRNA

profiling

Proteomics

DNA epigenetics

• Platform and clinical validation

• Archived specimen size and quality

• Informatics

• Turn-around time

• Disease group customer support

– Phased roll-out

– Lung, Colon, GBM, Breast

• Finances and billing

Challenges in Establishing a Clinical Genotyping

Program

ddNTP

ddNTP

ddNTP

loci of interest

Multiplex PCR Single Base Extension Reaction Capillary Electrophoresis

Electrophoretic Output

Increasing

molecular weight

Rela

tive

flu

ore

sce

nce

A B D C F E

SNAPSHOT Overview

SNAPSHOT Genotyping Assay

16 cancer genes – 120 described mutations

Gene Amino Acid – cDNA Residue Gene Amino Acid – cDNA Residue

AKT1 49G - E17 KRAS G12 - 34G KRAS G12 - 35G APC R1114 - 3340C KRAS G13 - 37G APC Q1338 - 4012C KRAS G13 - 38G APC R1450 - 4348C APC T1556fs* - 4666_4667insA NOTCH1 L1575 - 4724T NOTCH1 L1601 - 4802T BRAF V600 - 1798G BRAF V600 - 1799T NRAS G12 - 34G NRAS G12 - 35G CTNNB1 D32 - 94G NRAS G13 - 37G CTNNB1 D32 - 95A NRAS G13 - 38G CTNNB1 S33 - 98C NRAS Q61 - 181C CTNNB1 G34 - 101G NRAS Q61 - 182A CTNNB1 S37 - 109T NRAS Q61 - 183A CTNNB1 S37 - 110C CTNNB1 T41 - 121A PIK3CA R88 - 263G CTNNB1 T41 - 122C PIK3CA E542 - 1624G CTNNB1 S45 - 133T PIK3CA E545 - 1633G CTNNB1 S45 - 134C PIK3CA Q546 - 1636C PIK3CA Q546 - 1637A EGFR G719 - 2155G PIK3CA H1047 - 3139C EGFR T790 - 2369C PIK3CA H1047 - 3140A EGFR L858 - 2573T PIK3CA G1049 - 3145G EGFR E746_A750 - 2235_2249del EGFR E746_A750 - 2236_2250del PTEN R130 - 388C EGFR Exon 19 deletions PTEN R173 - 517C PTEN R233 - 697C FLT3 D835 - 2503G PTEN K267fs*- 800delA IDH1 R132 - 394C TP53 R175 - 524G IDH1 R132 - 395G TP53 G245 - 733G TP53 R248 - 742C JAK2 V617 - 1849G TP53 R248 - 743G TP53 R273 - 817C KIT D816 - 2447A TP53 R273 - 818G TP53 R306 - 916C

ERBB2 Exon 20 insertions

IDH1 R132 -394C

IDH1 R132 -395G

AKT1 49G – E17

7-plex Panel 1

KRAS34

EGFR2235_49F

EGFR 2573

NRAS181

PI3K1633 bCat94

bCat121

8-plex Panel 2

EGFR2235_49R

NRAS38

BRAF1799

NRAS182

PI3K263 bCat122

bCat95

TP53.742

5-plex Panel 3

NRAS35

EGFR2236_50F

EGFR2369

bcat133

PI3K1624

8-plex Panel 4 KRAS35

EGFR2236_50R

PTEN517

FLT3.2503

PI3K3139

NOTCH1.4724

NOTCH1.4802 TP53.733

SNAPSHOT V1

EGFR mutation

Glu746_Ala750del

(c.2235_2249del)

Normal

Lung cancer

SNAPSHOT v3

BRAF mutation

Val600Glu

(c.1799T>A)

Normal

Melanoma

SNAPSHOT v3

PIK3CA mutation

His1047Arg

(c.3140A>G)

Normal

Breast cancer

SNAPSHOT v3

KRAS 23%

No Mutation 42%

EGFR 15%

TP53 5%

IDH1 <1%

NRAS 1% BRAF 2%

HER2 2%

PIK3CA 4%

ALK 3%

CTNNB1 2%

AKT 1%

N=650

Mutational Profiling in Lung Adenocarcinoma

1

2

KRAS

56 isolated

(58 total)

EGFR

36 isolated

(50 total)

ALK

13

T790M

5

PIK3CA

5

TP53

1

1 1

1

1

4

2

APC

NRAS

BRAF

1

1 3

B-cat

Belinda Waltman/ Lecia Sequist

Lung Adenocarcinoma: Overlap of Mutations

Transmembrane receptor

tyrosine kinase involved in

epithelial development and

function

Mutations/genomic alterations

are common in human cancer

including in: 40% glioblastoma,

15% NSCLC

Kinase domain mutations in

lung ACA linked with non-

smoking

EGFR

Pre-treatment

3 months post-Iressa

Nakagawa K, Tamura T, Negoro S, Kudoh S, Yamamoto N, Yamamoto N, Takeda K, Swaisland H, Nakatani I, Hirose M,

Dong RP, Fukuoka M. Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine

kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid malignant tumors. Ann Oncol. 2003

Jun;14(6):922-30.

Gefitinib (Iressa)

Erlotinib

(Tarceva)

EGFR kinase domains inhibitors:

clinical response in 10% of patients

Sequist et al., J Clin Oncol. 2008 May 20;26(15):2442-9

High Response Rate to First Line Anti-EGFR Therapy

in Advanced EGFR-mutant Lung Adenocarcinoma


EGFR and Iressa Pan-Asia Study (IPASS)


EGFR and Iressa Pan-Asia Study (IPASS)

21-kDa GTPase involved in signal

transduction in MAPK pathway

Mutations are common in human

cancer including in: 90%

pancreatic ca, 50% colon ca, 30%

lung NSCLC

Mutations in KRAS are

“downstream” of EGFR; such

tumors would not respond to anti-

EGFR therapy

EGFR

KRAS Sequencing: What Drugs Not to Use

21-kDa GTPase involved in signal

transduction in MAPK pathway

Mutations are common in human

cancer including in: 90%

pancreatic ca, 50% colon ca, 30%

lung NSCLC

Mutations in KRAS are

“downstream” of EGFR; such

tumors would not respond to anti-

EGFR therapy

$204 per test, based on CPT codes

83890,83898,83894,83904x2,83912

Do the Large Benefits Justify the Large Costs of Adjuvant Breast Cancer Trastuzumab?

Bruce E. Hillner, Thomas J. Smith Journal of Clinical Oncology, Vol 25, No 6 (February 20), 2007: pp. 611-613

Trastuzumab Antibody to extracellular portion of HER2 $5,000/month

Erbitux Antibody to extracellular portion of EGFR $10,000/month

Gefitinib Small molecular tyrosine kinase inhibitor $2,000/month

EGFR

KRAS Sequencing: What Drugs Not to Use

Lung adenocarcinoma: modification of the 2004 WHO mixed

subtype to include the major histologic subtype suggests correlations

between papillary and micropapillary adenocarcinoma subtypes,

EGFR mutations and gene expression analysis. Motoi N, Szoke J, Riely

GJ, Seshan VE, Kris MG, Rusch VW, Gerald WL, Travis WD. Am J Surg

Pathol. 2008 Jun;32(6):810-27.

27/130 positives

9/27 classified with BAC features or pure BAC

Literature Bell: 4/9 BAC component

Varmus: 11/12 BAC component

EGFR Mutations –

Association with BAC

EGFR wt EGFR mutation

8

10

9

0

Non-mucinous

Mucinous

KRAS mutation

0

8

EGFR Mutations – Histology

Serine-threonine kinase immediately

downstream of KRAS in MAPK pathway

Mutations are common in human cancer

including in: 70% melanoma, 50% papillary

thyroid ca, 30% ovarian serous ca, 10% colon ca

Yousem et al. 2008 showed BRAF mutation in

5% of EGFR WT/KRAS WT lung adenocarcinomas; i.e. activating mutations

are mutually exclusive

Associated with papillary architecture

BRAF

38-kDa transcription factor

normally expressed in adult

thyroid and lung tissue and is

essential in lung development

Positive by IHC in >75% of non-

mucinous lung

adenocarcinomas

Most common focal

amplification in genome-wide

analysis

TTF1 may have a role in

pathogenesis

TTF1 (aka Nkx2.1)

Low grade adenocarcinoma of fetal

lung type

Generally associated with younger

age (4th decade) a good prognosis

Glycogen-rich glandular formations

Can occur in patients with FAP

CTNNB1 (beta-catenin)

KRAS mutation Primary

EGFR T790M Primary and acquired

MET amplification Primary and acquired

Lung cancer and EGFR TKI resistance mechanisms

KRAS mutation is associated with EGFR TKI

resistance

The T790M mutation causes

steric hindrance that prevents TKI binding

Mutations are common cause

of acquired TKI resistance

Following mutations in re-biopsy

or circulating tumor cells can

help guide therapeutic decisions

EGFR T790M mutation is associated with EGFR TKI

resistance

MET activation is associated with human cancer

Hereditary papillary renal cancer

Gastric carcinoma

Hepatocellular carcinoma

NSCLC

MET amplification mediates EGFR TKI resistance even in presence of EGFR sensitizing mutations

Day -7 Day 25

Dr. Ignatius Ou

MET-amplified NSCLC (<1% prevalence): Crizotinib

response

Crizotinib: Potent & selective ATP competitive oral inhibitor of MET

and ALK kinases and their oncogenic variants

~250 kb ~300 kb

t(2;5) ALK gene

breakpoint region

2p23 regionTelomere Centromere

3’ 5’

~250 kb ~300 kb

t(2;5) ALK gene

breakpoint region

2p23 regionTelomere Centromere

3’ 5’

ALK Rearrangements in NSCLC

Shaw et al., CCR 2009

13%

Dr. Ignatius Ou, UC Irvine

Rapid Clinical Response to Crizotinib

Tumor Responses to Crizotinib by Patient

50

20

–10

–40

–70

–100

Decre

ase o

r in

cre

ase fro

m b

aselin

e (

%)

PD

SD

PR

CR

Best Percent Change in Tumor Size

(n=105 evaluable patients) 60

40

20

– 20

– 40

– 60

– 80

–100

0

30% reduction

Camidge R et al. Poster 366 presented at the 35th ESMO, 2010

Timeline for PF2341066 and ALK in NSCLC

Identification of

PF2341066

PF2341066 Inhibits

ALK activity

PF2341066

demonstrates

cytocidal activity in

cells exhibiting ALK

fusion (Pfizer in

house)

PF2341066 activity in

cells exhibiting ALK

fusion in broad

screen (MGH-

McDermott)

Discovery of EML4-ALK

fusions in NSCLC

(CREST) Japan Science

& Technology Agency)

2007

PF2341066 FIP

May

2005 2006 2008 2009

Objective responses

demonstrated in ALK

fusion positive NSCLC

and IMT

Phase III study of

“Crizotinib” in ALK

positive NSCLC starts

2010 2011

FDA Approval of

Crizotinib in ALK

positive NSCLC

PROS

Commercial FDA-approved probes available

Not too expensive

Moderately easy to disseminate screening

Clinically validated

Poorly preserved tissues FAIL – not reported as negative (like

IHC)

CONS

Need FISH lab expertise, including pathologist involvement

(not just for cytogenetics labs or PhD-run labs)

FISH can be very tricky- genes are very close

ALK FISH Pros-Cons

ALK 29.3

EML4 42.3

Split signal

WT (non-split) signal

ALK FISH in NSCLC

Case 1

ALK 29.3

EML4 42.3

Split signal

WT (non-split) signal

ALK FISH in NSCLC

Case 1

ALK 29.3

EML4 42.3

Split signal WT (non-split) signal

ALK FISH results

Mino-Kenudson et al., CCR 2010

ALK IHC Comparison in NSCLC

Mino-Kenudson et al., CCR 2010

ALK IHC Comparison in NSCLC

PRO

Very rapid

Very cheap

Very easy to disseminate screening

CONS

Commercial antibodies sub-optimal

Poorly preserved tissues (especially biopsies) may give false

negative results due to loss of antigen- since no internal

controls there is no way to know that

ALK IHC Pros-Cons

ALK rearrangement – Histology - MGH experience -

Nishino M, Mark EG, Iafrate AJ, Mino-Kenudson M

Signet Ring Cells N %

None detected 38 32%

< 10% 43 36%

> 10% 39 32%

ROS1 rearrangements in NSCLC






ROS1 rearrangements in NSCLC: Crizotinib Response

Custom Automated Method for DNA Isolation from Tumor Archives

Genomic

TL-09-267 20 ng/panel DNA

TL-09-285 3.04ng/panel DNA

Genotype YR Location

Clinical questions/staging Inform-ative?

Answer

KRAS 35G>A, G12D 2011 RUL T3N0 vs T1aN0 x2 lesions Y T1 x 2

KRAS 182A>T, Q61L , BRAF 1798G>T, V600L 2011 RUL

KRAS 35G>T, G12V 2011 RLL T1aN0 vs T4N0 Y T1 x 2

EGFR 2582T>A, L861Q 2011 RUL

No mutation 2011 RML T1aN0 vs T4N0 Y T1 x 2

KRAS 34G>C, gly12arg 2011 RUL

KRAS 34G>T, G12C 2010 RLL T4N0 vs T1aN0 x2 lesion Y T1 x 2

BRAF 1397G>T, G466V, KRAS 37G>T, G13C 2010 RUL

KRAS 34G>T, G12C 2009a RUL T1aN0M1a vs T1aN0 x2 lesions Y T1 x 2

KRAS 35G>C, G12A 2009a LUL

KRAS 34G>T, G12C 2009b adrenal

KRAS 34G>C, G12R 2008 LLL Met vs. metachronous 2 primaries Y 2 primaries

No mutation 2010 RLL

No mutation 2008 LLL Met vs. metachronous 2 primaries Y 2 primaries

KRAS 34G>T, G12C 2010 RML

EGFR 2573T>G, L858R 2009 LLL Met vs. metachronous 2 primaries Y Metastases

EGFR 2573T>G, L858R 2011 RUL

No mutation 2007 RML Met vs. metachronous 2 primaries N -

No mutation 2010 RML

KRAS 35G>C, G12A 2011 RUL Met vs. metachronous 2 primaries Y 2 primaries

EGFR exon 19 (18bp) deletion 2011 LUL

No mutation 2009 LUL Met vs. metachronous 2 primaries Y 2 primaries

KRAS 34G>T, G12C 2010 RLL

KRAS 34G>T, G12C 2010 RML T1aN0 x2 vs T4N0 Y T1 x 2

BRAF 1799T>A, V600E 2010 RLL

TP53 742C>T, R248W; KRAS 35G>C, G12A 2010 LUL Met vs. metachronous 2 primaries Y 2 primaries

KRAS 37G>T, G13C 2010 RUL

Snapshot Genotyping to Resolve Staging Questions

Our knowledge of cancer genetics continues to grow rapidly

and clinical demand for genetic analysis is very high.

Molecular profiles are beginning to drive cancer therapy

decisions.

Clinical application of higher-throughput cancer genotyping

is a reality…waiting for next-gen sequencing.

Pre-screening of genetic subtypes can accelerate clinical trial progress.

Summary

Next in the Series of Free PHC Webinars


• The Pathologist’s Role in the Diagnosis and Treatment of Breast

Cancer in the Era of Personalized Healthcare

Wednesday, March 28, 11:00-12:00 pm Central

o Kenneth J. Bloom, MD, FCAP

Breast cancer treatment has been the poster child of personalized

medicine. Advances in molecular analysis has led to several

prognostic and predictive classifiers which are beginning to alter

therapy options for breast cancer patients, while the assessment of

hormonal and HER2 status continues to be essential in determining

eligibility for targeted therapy. This talk will provide insight into how

you can incorporate molecular pathology into your breast pathology

practice.

• Past Webinars Available Now Online at www.cap.org/institute

o Molecular Testing Selection Guidelines for Selecting Lung Cancer

Patients for EGFR and ALK Tyrosine Kinase Inhibitors

o Clinical Use of Whole Genome and Whole Exome Sequencing Today

o Validating Whole Slide Imaging Systems for Diagnostic Use in

Pathology

o The Why, What and How of Identifying Patients at Risk

o Molecular Diagnosis for Lung Cancer Patients

o Whole Genome Analysis as a Universal Diagnostic: A Pathologist’s

Perspective

o Next-Generation Sequencing for the Clinical Laboratory

• Go to www.cap.org/institute For All Upcoming Webinars!

Don’t Forget to Check Out Past Webinars!


http://www.cap.org/institute

http://www.cap.org/institute

Watch for publication in 2012…

• CAP/IASLC/AMP Molecular Testing Guidelines for

Selection of Lung Cancer Patients for EGFR and ALK

Tyrosine Kinase Inhibitors

o Archives of Pathology and Laboratory Medicine

o Journal of Thoracic Oncology

o The Journal of Molecular Diagnostics


CAP Learning – Other Molecular Oncology CME

Activities

74

© 2011 College of American Pathologists. All rights reserved. This document is confidential and may not to be reproduced or distributed without permission from CAP Learning.

Course Learning Objectives Molecular Pathology: An Introduction to DNA

Technology and Diagnostic Applications (SAM

eligible)

CME/SAM – 2.0

-Identify potential application of molecular pathology

-Describe the chemical structure and properties of DNA and RNA

-Explain the different types of genetic variations

-Identify diagnostic techniques in molecular pathology

Archives Applied: KRAS (SAM eligible)

CME/SAM – 1.0

-Identify whether anti-EGFR therapy is an appropriate treatment method for a patient

case

-Describe advantages and limitations of specific KRAS mutation testing methods

-Identify the appropriate elements to include in the report for a patient case

-Describe the current role of KRAS mutation testing for management of patients with

metastatic colorectal cancer

Archives Applied: Molecular Test Validation

(SAM eligible)

CME/SAM = 1.0

-Identify the appropriate:

-test parameters for an analytic quantitative or qualitative test

-clinical performance characteristics for test validation

-performance characteristics for a quantitative or qualitative test

-elements to include in test validation documentation

-Identify pre-validation considerations for a proposed molecular pathology test

Archives Applied: Molecular Diagnostics of Soft

Tissue Tumors (SAM eligible)

CME/SAM = 1.0

-Recognize which genetic alterations seen in soft tissue tumors are amenable to

molecular diagnostics using routine clinical genetic approaches

-Describe characteristics of chromosomal translocations in soft tissue sarcomas

Identify the advantages and limitations of conventional cytogenetic analysis for soft

tissue tumors

-Identify approaches for assessing inactivation of a tumor suppressor gene, for

example the SMARCB (INI1) in soft tissue tumors

-Identify the advantages and limitations of molecular cytogenetic analysis for soft

tissue tumors


Activities

75


Course Learning Objectives Molecular Testing for AML Cases

CME – .5

-Recognize molecular oncology knowledge and skills required of pathologists that can

mitigate problems and enhance patient care with respect to specimen handling

-Realize the effects that appropriate specimen handling and communication throughout

all stages of diagnosis have in enhancing patient care

-Reflect on your own knowledge and skills in specimen handling and patient care, and

identify what can help you and your practice be more effective in these areas of

molecular oncology

BRAF Mutation Testing in Melanoma

CME – .5

-Follow quality assurance policies and procedures to ensure adequate sample collection

and proper handling techniques for molecular oncology tests

-Use appropriate result reporting principles for incorporating molecular test results into

surgical pathology reports

Molecular Testing for Lymphoma Cases

CME - .5

-Recognize molecular oncology knowledge and skills required of pathologists that can

mitigate problems and enhance patient care with respect to specimen handling

-Realize the effects that appropriate specimen handling and communication throughout

all stages of diagnosis have in enhancing patient care

-Reflect on your own knowledge and skills in specimen handling and patient care, and

identify what can help you and your practice be more effective in these areas of

molecular oncology

Adenocarcinoma and EGFR and KRAS

Mutation Testing

CME - .5

-Recognize the indications for EGFR and KRAS molecular testing as they pertain to non-

small cell lung cancer

-Interpret molecular diagnostic test results and correlate them with the diagnosis

pertaining to non-small cell lung cancer


Activities

76


Course Learning Objectives Molecular Diagnosis of Ewing Sarcoma

CME - .5

-Review sample requirements and handling for RT-PCR, FISH, and cytogenetic analysis

as they pertain to evaluating mesenchymal neoplasms

-Describe the advantages and limitations of genetic approaches commonly used in

the classification of mesenchymal neoplasms to include conventional karyotyping,

FISH, and RT-PCR

BPFT Testing Self Study

CME /SAM – 2.5

-Explain the ASCO-CAP ER/PR Testing Guidelines and their implications for lab

procedures, test results and patient care.

-Explain the ASCO-CAP HER2 Testing Guidelines and their implications for lab

procedures, test results and patient care.

-Determine if the assay and tissue sample are appropriately matched per the

ASCO/CAP Guidelines.

-Explain the biology of fixation interactions with assay performance.

-Explain the potential use of molecular analysis in patient care decisions.

an mitigate problems and enhance patient care with respect to specimen handling

HER2 FISH Test Interpretation Accuracy

CME/SAM – 1.5

-Accurately interpret HER2 FISH tests.

-Correct for HER2 FISH interpretative errors.

-Recognize the relationship between HER2 FISH test results and patient treatment.

BPFT Reporting

CME/SAM – 1.5

-Apply the ASCO-CAP ER/PR and HER2 Guideline criteria to all reports in a

standardized manner.

-Create consistent, standardized and integrated reports.

-Remediate inconsistent data and provide a resolution in an integrated report.

-Create patient friendly reports.

-Use formatting techniques to create clear and understandable reports.


Activities

77


Course Learning Objectives ER IHC Test Interpretation Accuracy

CME/SAM – 2.0

-Plan and perform a proper ER IHC test validation.

-Accurately perform and interpret ER IHC tests, including the proper evaluation of appropriate

controls and test tissues.

-Evaluate and integrate ER staining patterns with clinical and morphologic findings.

-Identify the relationship and impact of ER IHC test results on patient treatment.

HER2 IHC Test Interpretation Accuracy

CME/SAM – 2.0

-Plan and perform a proper HER2 IHC test validation in accordance with ASCO-CAP guidelines

for HER2 testing.

-Accurately perform and interpret HER2 IHC tests, including the proper evaluation of

appropriate controls and test tissues.

-Evaluate and integrate HER2 staining patterns with clinical and morphologic findings to help

improve concordance with HER2 FISH results.

-Identify the relationship and impact of HER2 IHC test results on patient treatment.

Reminder: CAP Learning Portal Launches

78

© 2011 College of American Pathologists. All rights reserved. This document is confidential and may not to be reproduced or distributed without written permission from CAP Learning.

CAP Learning Portal

• The CAP Learning Portal landing page on the cap.org website replaces the current Education Programs page design. A user must log into cap.org in order to access further information.

• The CAP Learning Portal includes new tools to support the learning needs of pathologists such as:

o Learning Options search/catalog

o Competency Model for Pathologists

o Personal Progress Check (member only tool)

o My Learning Plan (member only tool)

o Help Center

• Benefits

Increase effectiveness to plan and manage learning Increase efficiency to target learning needs and identify premium learning solutions Increase satisfaction with learning solutions that meet specific learner needs

Increase capability to maintain professional certifications

To learn more…

79

© 2011 College of American Pathologists. All rights reserved. This document is confidential and may not to be reproduced or distributed without written permission from CAP Learning.

• For more details and to register for/access Molecular Oncology educational offerings:

1. Log in to the cap.org website

2. Click on Launch Portal

3. Click on the Learning Options tab

4. Type Molecular Oncology in the Search box

A list of available learning options displays

THANK YOU!

Thank you for attending our webinar

“Molecular Diagnosis of Lung Cancer”

by A. John Iafrate, MD, PhD.

For comments about this webinar

or suggestions for upcoming

webinars, please contact

Jill Kaufman, PhD,

Director of Personalized Health Care at

[email protected]

NOTE: There is no CME/CE credit available for

today’s free webinar. 80 © 2011 College of American Pathologists. All rights reserved.

mailto:[email protected]

Documents

Molecular Diagnosis of Lung CancerMolecular Diagnosis of Lung Cancer A. John Iafrate, MD, PhD ... DNA mutations DNA chromosomal alterations mRNA and miRNA profiling Proteomics