Transcript DYSPNEA AND THE CANCER PATIENT

The Importance of Tissue Banking and Tissue
Research:
Presentation on May 5, 2004 at
“Conflicts of Interest, Privacy/Confidentiality, and Tissue
Repositories: Protections, Policies, and Practical
Strategies”
Mark E. Sobel, M.D., Ph.D.
Executive Officer,
American Society for Investigative Pathology
[email protected]
www.asip.org
Copyright © 2004, American Society for Investigative Pathology
The Era of Molecular Medicine
Molecular techniques, information
generated from the Human Genome
Project, and advances in information
technology are transforming the:
• public’s fears and expectations
• practice of medicine
Copyright © 2004, American Society for Investigative Pathology
“Eye on the Prize”
Improve the public’s health
• Conduct biomedical research to
increase knowledge and understanding
of biological processes.
• Respect subjects’ rights and personal
autonomy; minimize harm.
Copyright © 2004, American Society for Investigative Pathology
Use of Human Biological
Materials in Research
Human subject protections are applicable
not only to clinical trials but also to the use
of human biological materials in research
studies, including basic science projects.
Copyright © 2004, American Society for Investigative Pathology
Human Biological Materials
HBMs
• Tissue samples
• Blood, sputum, urine, bone marrow,
etc.
• Freshly obtained and archived
materials
Copyright © 2004, American Society for Investigative Pathology
Repositories
• Tissue banks
• Stored blood/urine samples
• Freezers containing HBMs under individual
control of principal investigators
• Histologic slide files
• Eiseman, E. and Haga, Susanne B., “Handbook
of Human Tissue Sources,” Rand, 1999.
Copyright © 2004, American Society for Investigative Pathology
Requirements of Repositories
•
•
•
•
•
•
Security of samples
IRB oversight
Record keeping for informed consent
Confidentiality
Anonymize samples
Increased workload !!
Copyright © 2004, American Society for Investigative Pathology
Challenges
• Educating researchers
• Use of previously archived HBMs that were
obtained without consent
• Re-use of HBMs
• Utility of anonymized samples
• Utility of autopsy specimens
• Assessment of risk by IRBs:
– What is genetic research?
– Is “genetic” research necessarily high risk?
• Demands on Tissue Repositories
Copyright © 2004, American Society for Investigative Pathology
Educating Researchers
•
•
•
•
Clinical research
Translational research
Basic science research
What is a Repository?
Copyright © 2004, American Society for Investigative Pathology
Anonymized Samples
• Value in basic science studies
• Disadvantages for translational/clinical
research
– Studies not optimal
– Inability to perform long-term follow-up or
prognostic studies
– Inability to request more of the same sample or
different samples that don’t duplicate the original
– Clinically useful information cannot be conveyed
(rare)
Copyright © 2004, American Society for Investigative Pathology
Classifying HBMs:
Assessment of Risk
• Unidentifiable
• Anonymous
• Anonymized
• Identifiable
• Coded (Linked)
• Identified
Copyright © 2004, American Society for Investigative Pathology
Use of HBMs in “Genetic” Research:
Assessment of Risk
• Germline
–
–
–
–
Inheritability
Implications for immediate and extended family
Implications for ethnic group
Use of “normal” tissues
• Somatic cell- less risk
– Acquired mutations
– Use of diseased tissues
– No implications for family
Copyright © 2004, American Society for Investigative Pathology
Classifying HBMs:
Assessment of Risk
• Basic Science Studies
• Source for substrates
• Biochemical studies
• Translational Research
• Clinical Research
Copyright © 2004, American Society for Investigative Pathology
HBMs in Research
David Korn, “Contribution of the Human
Tissue Archive to the Advancement of
Medical Knowledge and the Public
Health,” in “National Bioethics Advisory
Commission Report on Research Involving
Human Biological Materials: Ethical Issues
and Policy Guidance,” Volume II, January
2000.
Copyright © 2004, American Society for Investigative Pathology
HBMs in Research: Early History
• Birth of the discipline of pathology: Autopsies
performed by physicians on their deceased
patients- Renaissance Italy
• Origin of the science of pathology: systemic
study of the causes, mechanisms and natural
history of diseases- 19th century GermanyRudolph Virchow- the application of light
microscopy to the study of diseased HBMs and
the “cell theory of disease”
Copyright © 2004, American Society for Investigative Pathology
HBMs in Research
• Historical use of archived specimens
• Re-use of specimens
– Pathologists and the histological slide file
• Increased demand for tissues
– Tissue microarrays
– Gene expression arrays
Copyright © 2004, American Society for Investigative Pathology
Re-use of Archived Specimens
• DES:
– 1960s: Robert Scully at MGH
– Unusual tumor of the vagina- “clear cell
adenocarcinoma of the vagina”
– Mothers had been treated with the
nonsteroidal estrogenic hormone
diethylstilbestrol during their pregnancies
– Establishment of a national registry
– Early detection and cure rate of 90%
Copyright © 2004, American Society for Investigative Pathology
Re-use of Archived Specimens
• Hepatic Angiosarcoma
– 1940s-1950s: recognition of carcinogenic
potential of occupational and environmental
agents from suspicions of a pathologist
observing small clusters of unusual
neoplasms and thinking about shared
histories
– Plastic starting materials: vinyl chloride and
polyvinyl chloride
– Thorotrast (contrast agent)
Copyright © 2004, American Society for Investigative Pathology
Re-use of Archived Specimens
• Bronchopulmonary Neoplasia
– Oscar Auerbach, East Orange, NJ
– Histopathological changes in the lungs of
autopsied smokers compared to lung cancer
– New York Times obituary: “pathologist who
found the first evidence in human lung tissue
of a link between cancer and smoking”
Copyright © 2004, American Society for Investigative Pathology
Archived Specimens
• Uranium Mining
– Geno Saccomanno
– Archive of pulmonary pathological and
cytological specimens from underground
uranium workers
– Bronchogenic carcinoma
– Apply direct, rapid modern detection
technologies for candidate markers to
existing specimens
Copyright © 2004, American Society for Investigative Pathology
Autopsy Specimens: Brain
• Prion Diseases
• Cognitive Dementia
– Altzheimer’s disease
Copyright © 2004, American Society for Investigative Pathology
Molecular Genetic Methods
• Lymphomas:
– Sklar and Cossman- 1970s
– Knowledge of normal genetic maturation of
lymphocytes into immunocompetent cells
– Proliferative lymphoid lesions bearing
different histopathologic diagnoses
– Fixed and frozen tissue collections
Copyright © 2004, American Society for Investigative Pathology
Molecular Virology
• Viral Neoplasias
– Burkitt’s Lymphoma: childhood lymphoma
prevalent in central Africa
– 1970s- Epstein and Barr show that Burkitt’s
lymphoma cells harbor a virus
– Infectious mononucleosis
– Link between infectious mononucleosis and
Hodgkin’s lymphoma
Copyright © 2004, American Society for Investigative Pathology
Molecular Virology
• Human Papilloma Virus (HPV)
– Pap smears and collections of specimens
– Sequential patterns of progression from
normal to dysplastic to neoplastic changes in
cervical epithelial cells
– HPV difficult to culture
– New diagnostic molecular tests for
“aggressive” subtypes
Copyright © 2004, American Society for Investigative Pathology
Molecular Virology
• Influenza
– AFIP in 1990s
– Samples of autopsied lung tissue from 198
soldiers who died of the “Spanish Flu” in
1918
– Understanding lethality
– Similarity to modern strains
Copyright © 2004, American Society for Investigative Pathology
Molecular Virology
• HantaVirus
– 1993 cluster of deaths in the American
Southwest
– Suspicious clinician, astute epidemiologist,
observant Navajo elders, and specimen
archives
– CDC libraries of viruses, viral proteins and
serum specimens
– Pulmonary tissues from the autopsied
victims
Copyright © 2004, American Society for Investigative Pathology
Molecular Genetic Methods
• APC gene: adenomatous polyposis coli
– Frozen specimens of colorectal cancers
– Banked DNA specimens from patients with
familial adenomatous polyposis
– Chromosome 5q
Copyright © 2004, American Society for Investigative Pathology
Molecular Genetic Methods:
Cancer Genome Anatomy Project
• 1997- CGAP launched by NCI
• Classify tumor genes by the type of cancer cell
they come from and by degree of malignancy
• Comprehensive molecular characterization of
cancer and precancerous cells
Copyright © 2004, American Society for Investigative Pathology
Conclusion (Korn Report):
“Now more than ever before, the dramatic
growth of the biomedical knowledge base
and the applicability of powerful new
technologies to tiny samples of diseased
human tissues offer promise of major
breakthroughs in understanding – and
effectively managing- some of the most
intractable diseases of humankind. (cont’d)
Copyright © 2004, American Society for Investigative Pathology
Conclusion (Korn Report):
To achieve that promise, public policy must
continue to encourage the accumulation of
the human tissue archive and facilitate its
accessibility for medical research.”
Copyright © 2004, American Society for Investigative Pathology