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Michael J. Becich, MD PhDChair and Professor, Department of Biomedical Informatics (see http://www.dbmi.pitt.edu)

UPMC Cancer Pavilion, Room 3055150 Centre Avenue

Pittsburgh, PA  15232e-mail - becich@pitt.edu

phone - 412-623-3941

National Mesothelioma Virtual Tissue Bank (NMVB) (http://www.mesotissue.org)

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Overview:

The National Mesothelioma Virtual Bank (NMVB) provides de-identified annotated mesothelioma biospecimens to the mesothelioma research community.

The NMVB database allows a user to query the biospecimen resource to identify cohorts for translational research.

We collect retrospective and prospective mesothelioma cases at three major sites New York University (NYU), University of Pennsylvania (U. Penn) and University of Pittsburgh Medical Center (UPMC).

Key to this resource is continued annotation of mesothelioma biospecimens including demographics, epidemiological, clinicopathology, follow-up and recurrence data for all biospecimens collected.

We then provide well-annotated high quality mesothelioma biospecimens and data to approved researchers via a Letter of Intent – see http://www.mesotissue.org/apply.cfm

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Expansion of Biospecimen Resource: NMVB has been funded for the next five years to

collect annotated mesothelioma biospecimens and distribute them to investigators for basic and clinical science research.

New Collaborator: Mount Sinai School of Medicine (MSSM) is brought on board to expand the specimen collection to meet the research requirements.

Two tissue microarrays have been developed and are available for investigators.

Marketing efforts are expanded to provide information regarding the resource to a larger community of researchers via mass marketing e-mails, publications and national/international conferences.

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Specimen Collection:

Tissue bank protocols are followed in the collection and storage by tissue bank technicians.

Specimen Types: Tissue Microarray with Clinical Data Annotation Fresh Frozen Tissues Blood Products: Serum, RBC, Plasma, Whole

blood, Buffy Coat, etc… Paraffin embedded blocks

NMVB Collection of Blood Samples

Plasma, 293, 25%

Serum, 290, 26%PMBC, 73, 7%

Whole Blood, 211, 19%

Buffy Coat, 111, 10%

Red Blood Cell, 143, 13%

Biospecimen

CTTK

Questionnaire & consent

RIS

TBIS

TBIS: Tissue Bank inventory System,

RIS: Registry Information System,

CTTK: Clinical Trial Tool Kit,

NMVB: National Mesothelioma Virtual Bank

NMVB Database

INSTITUTIONAL

FIREWALL

Web-Based User Interface

Tissue Banker

Cancer Registrar

Clinical Nurse Coordinator

Database Administrator

External Study Coordinator

Investigator

Patient

Mesothelioma Consenting, Tissue Banking and Clinical Data annotation workflow

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Nurse coordinator notifies Health Sciences Tissue Bank (HSTB) personnel prior to the patient’s surgery of NMVB tissue candidate and follows up by faxing a

consent to the HSTB.

E-mail notification to Post Doc and Project Coordinator on the up coming surgery.

Surgical tissue is picked up at the OR and brought to the Gross Dissection room and is triaged under the auspices of a

Pathologists’ Assistant.

The Surgical tissue is assigned a NMVB Study number.

Each portion received from the Pathologists’ Assistant (determined by amount

and size of tissue) is to be divided into three portions

Bulk Frozen Formalin Tissue

Fresh frozen OCT

Bulk frozen is kept in bitran bag and stored in -80°C.

FF OCT is stored in a heat sealed bag

@ -80°C

Taken to research histology lab for processing to formalin

fixed paraffin embedded (FFPE)

NMVB Tissue Bank Tissue Collection & Processing Protocol

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Nuncs should be labeled and aliquot as shown below and record on specimen sheet:

2 WB (whole blood – purple top before spinning)2 B (buffy coat)2 R (red blood cells)10-20 P (plasma)10-20 S (serum)

Research nurse coordinator call the tissue bank when patient is consented and pre-op, operative and post-op blood samples are drawn

Blood is tubed to Gross Dissection Room in the Department of Pathology

Tissue bank tech. receives 2-3 small purple tops and 1-2 large red tops along with a consent for the patient.

Nunc vials for the separated blood products are labeled with the NMVB Study# by

tissue bank technician

Before the purple tops are centrifuged, aliquot 2 nuncs with whole red blood.

All peripheral blood tubes are put through the centrifugation process.

Purple top yields plasma, buffy coat and red blood cell

aliquots.

Red top yields serum aliquots.

NMVB Tissue Bank Blood Products Collection & Processing Protocol

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NMVB Total Accruals:

Total Number of cases 967

Total Number of Specimens 1198

Total Number of Blocks 881

Total Accrual Analysis/Year (Cumulative):

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YearRetrospective

CasesProspective

CasesOverall NMVB

Total

2006 515 8 523

2007 574 61 635

2008 594 116 710

2009 663 173 836

2010 668 235 903

2011 (to date) 677 290 967

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Percentage of contribution / Each Site:

SiteRetrospective cases

Prospective Cases

Number of Cases Contributed

% contribution

NYU 157 85 242 25.5%

U. Penn 121 86 207 21.5%

UPMC 399 199 518 52%

Total 678 267 967 100%

523

635710

836903

967

0

100

200

300

400

500

600

700

800

900

1000

Number of cases

2006 2007 2008 2009 2010 2011 (todate)

Year

NMVB Accrual / Year

Accrual Trend

0

200

400

600

800

1000

1200

Year Increase inAccrual

112 75 126 67 63

Number of Cases 523 635 710 836 903 967

2006 2007 2008 2009 20102011 (to

date)

Number of Mesothelioma Cases for Each Age Group at Diagnosis

8 23

84

210

335

223

63

30

50

100

150

200

250

300

350

400

21-30 31-40 41-50 51-60 61-70 71-80 81-90 Greaterthan 90

Age Range

Num

ber

of C

ases

Vital Status

Alive, 179, 19%

Dead, 528, 54%

Unknown, 260, 27%

Mesothelioma Cases With Substance Exposure

Asbestos, 367, 38%

Other, 117, 12%

Non-Asbestos, 483, 50%

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NMVB Tissue Microarrays (TMAs)

Tissue Microarray (TMA) is used to examine the distribution of marker molecules in hundreds of different tissues displayed on a single slide.

UPMC TMA: 41 Mesothelioma cases. 36 cases have tissue cores from the primary lesion, 4 patients have tissue cores from a metastatic lesion and 1 patient has tissue cores from both the primary and metastatic lesions

U. Penn TMA: 4 TMA slides contain 61 mesothelioma cases. The TMA slides hold tissue core of primary, metastatic mesothelioma and control samples.

NYU TMA: 37 cases have been included in the development of TMA which included primary metastatic, mixed lesions and control sample.

TMA data excel, XML and maps files are available on the web site (www.mesotissue.org)

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Letter of Intent (LOI) Status Report

Total Number of Requests: 19

– Approved LOI 16

– Completed 15

– Specimens Request In Process: 3

– LOI request on Hold: 0

– Rejected/Closed 2

Average turnaround from initial request to getting specimens is about 6 weeks.

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http://www.mesotissue.org/

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Marketing Efforts:NMVB resource is marketed in the following major

meetings: United States and Canadian Academy of Pathology (USCAP) American Medical Informatics Association (AMIA) American Association for Cancer Research (AACR) Meso Foundation Annual Meetings (2008, 2009 & 2010) Pathology Informatics (2009 & 2011)

Publications:Amin W, Parwani AV, Schmandt L, Mohanty SK, Farhat G, Pople AK, Winters SB, Whelan NB, Schneider AM, Milnes JT, Valdivieso FA, Feldman M, Pass HI, Dhir R, Melamed J, Becich MJ. National Mesothelioma Virtual Bank: a standard based biospecimen and clinical data resource to enhance translational research. BMC Cancer. 2008 Aug 13;8(1):236.

Mohanty SK, Mistry AT, Amin W, Parwani AV, Pople AK, Schmandt L, Winters SB, Milliken E, Kim P, Whelan NB, Farhat G, Melamed J, Taioli E, Dhir R, Pass HI, Becich MJ. The development and deployment of Common Data Elements for tissue banks for translational research in cancer - an emerging standard based approach for the Mesothelioma Virtual Tissue Bank. BMC Cancer. 2008 Apr 8;8:91.

Wilson RA, Chapman WW, Defries SJ, Becich MJ, Chapman BE. Automated ancillary cancer history classification for mesothelioma patients from free-text clinical reports. J Pathol Inform. 2010 Oct 11;1:24.

Kang HP, Borromeo CD, Berman JJ, Becich MJ. The tissue microarray OWL schema: An open-source tool for sharing tissue microarray data. Journal of Pathology Informatics. 2010; 1.

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Acknowledgment:Collaborators:

Center for Disease Control and Prevention (CDC) National Institute of Occupational Safety & Health (NIOSH) University of Pittsburgh (UPMC), Pittsburgh, PA University of Pennsylvania (U. Penn), Philadelphia, PA New York University (NYU), New York City, NY Mesothelioma Foundation (Meso Fndn) Mount Sinai School of Medicine (MSSM) Insulators Union Tissue Bank (Led by James Grogan, President) University of California San Francisco (UCSF)

NOTE: We are currently exploring expanding the network in 2011 with the University of Hawaii Mesothelioma SPORE (and UCSF).

Leadership:Steven Abelda, MD (U Penn) James Luketich M.D (UPMC)David Bartlett, MD (UPMC) Jonathan Melamed MD (NYU)Michael J. Becich MD, PhD (UPMC) Harvey I. Pass MD (NYU)Michael Feldman MD (U Penn) Arjun Pennathur, MD (UPMC)Kathy Wiedemer (Meso-Fndn.) James Pingpank, MD (UPMC)Raja Flores, MD (MSSM) David Burstein, MD (MSSM)Steve Levin, MD (MSSM) Andrew Todd, PhD (MSSM)