Fulfilling Biospecimen Needs for Translational Research Around the World
The Biopathology Center (BPC) aims to excel in long-term acquisition and storage of cancer-related tissue specimens and associated data in support of cutting-edge research.
The BPC is primarily government-funded and partners with multiple research organizations to establish a significant infrastructure to support excellence in tissue banking, testing and distribution. Partnering investigators represent The Research Institute at Nationwide Children’s Hospital and national cooperative cancer groups and research organizations including:
The COG Biopathology Center (BPC) at The Research Institute of Nationwide Children's Hospital maintains the largest pediatric specimen bank in the nation. The BPC houses the COG Solid Tumor Tissue Bank, Pathology Center and the Acute Lymphoblastic Leukemia and the Neuroblastoma Reference Laboratories. The Biopathology Center serves as the Children's Oncology Group (COG) effector arm of the COG Pathology Discipline Committee. [more...]
The BPC began accruing specimens in 1989 and now contains tissue from more than 32,000 children with childhood cancer and other diseases. The BPC receives cancerous tissues from over 500 hospitals in the United States and Canada, as well as New Zealand, the Netherlands, Australia and Switzerland. Tissues from approximately 90 percent of pediatric solid tumor cases and half of the leukemia cases found in the United States and Canada are sent to the BPC.
The overall cure rate for pediatric cancer is 60%. The BPC plays a crucial role in the world of pediatric research by providing specimens for pediatric cancer and disease research. The BPC annually distributes more than 15,000 cancer-related specimens to COG-approved investigators through the BTRC application process. The last five years have also resulted in over 200 new publications generated by BPC activities including molecular studies in renal tumors, brain tumors, neuroblastoma and soft tissue sarcomas.
The BPC, which coordinated central pathology reviews for the Children's Cancer Group for over 30 years, now provides central pathology review services for all patients within the COG. The BPC receives cancer cases from patients registered on Children's Oncology Group protocols and then sends slides to expert pediatric pathologists around the country for confirmation of diagnosis. All new COG phase III protocols include the BPC as the central coordinating center for pathology review activities and banking/biology studies as appropriate.
The BPC provides procurement, shipping, processing, distribution, and repository services for the COG, its affiliated institutions, and researchers. In addition, the BPC provides protocol-related molecular testing. The BPC provides education and assistance to COG members on topics such as protocol requirements, specimen collection, and shipping regulations. The BPC assists the Study Development Office of the COG in the development of protocols involving pathology review and tumor procurement.
At the semi-annual COG meetings the staff of the BPC facilitates pathology review by providing virtual microscopy (VM) as well as a microscope room for education and to conduct on-site review. In addition, the BPC provides on-site review training sessions of pathologic materials by review pathologists and instructs young investigators at the BPC.
The BPC, has several tissue microarrays (TMA) available or in development on both solid and liquid (leukemia) tumors. Investigators can request slides from these arrays by completing the appropriate application, signing a Data Use Agreement and submitting their institutional IRB approval. Once the request is approved the slides will be distributed.
The Biopathology Center (BPC) is currently working on digitizing all slides received related to both rhabdomyosarcoma and neuroblastoma cases and making these slides available for web-based pathology review.
By working with the Children's Oncology Group, the BPC is able to correlate research data with specimen diagnosis and patient outcome to complete cutting-edge translational research that brings molecular genetic discoveries to the patient bedside.
The Cooperative Human Tissue Network (CHTN) is a group of six member institutions, supported the National Cancer Institute, that collect and distribute tissue to researchers across the United States and Canada. Since its establishment in 1987 the CHTN has provided more than 500,000 high quality specimens from a wide variety of organ sites to over a thousand investigators. Basic and developmental studies in numerous areas of cancer research have been facilitated by the availability of these specimens. [more...]
The Pediatric Division of the CHTN is located at the Children's Research Institute in Columbus, Ohio. From 1987 to 1989 the Pediatric Division provided pediatric tissues to the network as a subcontract of Ohio State University, but has been a separate division since 1989. The Pediatric Division provides pediatric tissues nationally and internationally to investigators located primarily within North America. The five adult divisions divide the same service area up geographically. In the first five years of its existence, the division provided over 1,400 tissues to 70 investigators, with the main source of tissues coming from 25 hospitals within the Children's Cancer Group.
The number of participating hospitals, specimens dispersed, and investigators served grew exponentially in 1994 as the Pediatric Division of the CHTN forged an alliance with three of the four major pediatric cancer groups, Children's Cancer Group (CCG), Intergroup Rhabdomyosarcoma Study Group (IRSG), and National Wilms' Tumor Study Group (NWTSG) to procure and distribute their collective pediatric cancer specimens to investigators. In 2000, all pediatric cooperative groups (including CCG, IRSG, NWTSG, and now the Pediatric Oncology Group, or POG) merged into a new unified Children's Oncology Group (COG).
Available specimens include tumor, diseased, and normal tissue. Tissues and fluids can be obtained from both surgical resections and autopsies. Tissue specimens are processed by three standard methods, but the researcher can request other types of processing. The standard processing methods are: fresh (in media, saline or dry), snap frozen (in foil or in OCT embedding compound) and fixed and embedded in paraffin. The paraffin embedded tissue can be processing into stained or unstained slides.
The emphasis is now, and will continue to be, on getting more and more specific information from less and less material. It is now possible to routinely screen thousands of genes on a single chip. The "one-in-a-million" tumor cell circulating in blood or bone marrow can now be detected utilizing polymerase chain reaction (PCR), despite its absence of detection by the human eye. We now have the ability via novel laser microdissection technique to sample lesions less than 1mm in size, specifically harvest the cells of interest from routinely-prepared surgical pathology material, and determine if a genetic abnormality of interest is present or absent. Hundreds of such lesions embedded as microarrays in a paraffin block may facilitate screening for multiple markers of malignancy.
Cancer remains the leading cause of death by disease in the pediatric age group (childhood and adolescence) in North America despite the fact that its overall cure rate exceeds 70%. Most pediatric cancer is genetically based, and in certain types-such as neuroblastoma, brain tumors and soft tissue sarcomas-discovery and analysis of genetic mechanisms may facilitate studies to improve what are currently abysmal survival rates. The pediatric cooperative groups are well organized and capture some 94% of childhood cancer patients (versus some 2% of patients captured by adult cooperative groups).
The Biopathology Center (BPC) serves as the Tissue Bank for the Gynecologic Oncology Group (GOG). Ovarian cancer accounts for nearly 50% of all deaths from cancer of the female genital tract and is the fifth leading cause of cancer deaths in American women. There are over 14,000 deaths and more than 23,000 diagnoses of ovarian cancer in the United States annually. As such, the disease is the most frequently fatal malignancy arising in the female reproductive system. Most diagnoses are made in advanced stage patients, and although these patients frequently respond to surgery and chemotherapy, their disease usually recurs and is resistant to additional treatment. [more...]
Earlier detection and diagnosis should result in a considerable decrease in ovarian cancer mortality since survival is highly related to stage at diagnosis. In 1990, the Organ Systems Workshop on Ovarian Cancer articulated the need for an ovarian cancer resource to facilitate research to improve prediction of response to therapy, identify prognostic indicators, and identify markers useful for early detection. Following this recommendation, the NCI GOG Tissue Bank was established in 1991 to provide researchers with tissue and serum, with associated clinical information, from patients with ovarian carcinoma.
Endometrial and cervical cancers also represent major sources of cancer-related morbidity and mortality for American women. There are approximately 36,000 new cases of uterine corpus cancer with 6,500 deaths, and 13,000 new cases of invasive cervical cancer with 4,650 deaths annually. In 1997 the bank was opened to include cervical and uterine corpus tumors from patients on GOG banking and treatment protocols. Since 1998, over 600 cases of cervical cancer and 1200 cases of endometrial cancer have been snap-frozen and banked.
The Tissue Bank was initially a supplement to an existing Pediatric Cooperative Human Tissue Network (CHTN) grant as a pilot study, but the program now functions as an independent component of the GOG under the title of the GOG Tissue Bank. This organization works closely with individual investigators in the GOG as well as those in university, private and governmental laboratories in promoting translational studies leading to an enhanced understanding of cancer. More than 70,000 specimens have been distributed to 146 investigators in the 14 years of the Bank's existence.
The GOG Tissue Bank began with two subdivisions. One, the External Bank, is for all investigators regardless of institutional affiliation. The specimens collected are both tumor and normal tissue with a baseline amount of generic clinical follow up data captured as part of the GOG-136 generic banking protocol. The second, the Internal Bank, is for the collection, organization and distribution of specimens to investigators studying translational research questions as part of GOG clinical trial protocols. These specimens are linked with detailed data from each clinical trial in order to deal with the translational issues considered in the protocol.
Access to the GOG Tissue Bank is controlled by the GOG's Tissue Utilization Subcommittee (TUS) within the Committee on Experimental Medicine (CEM). The CEM consists of representative GOG members, outside scientists, and the NCI representatives. Researchers who need tissue, clinical and pathologic information and outcome data are expected to collaborate with the GOG in order to protect patient privacy rights and ensure appropriate use of tissue and data resources.
The Biopathology Center (BPC) serves as the central repository for tumor and blood specimens collected from a group of 10 studies that make up the Cancer Therapy Evaluation Program (CTEP) supported Molecular Targeted Combinations Correlative (MTC²) project. These studies are managed by a variety of institutions and cooperative groups. The studies involve diseases such as Renal Cell, Glioblastoma Multiforme, and Melanoma. The BPC joined CTEP in this project in May 2005. [more...]
The samples collected for these protocols include paraffin material, snap frozen solid tissue, and blood products. Collection of blood takes place with every patient; however, solid tumor tissue availability varies. The goal is to collect as many samples as possible from these patients to identify prediction markers.
The tumor specimens are sent from participating sites directly to the BPC for Quality Control (QC), which includes confirmation of tumor and sample attributes. An adult pathologist(s) with expertise in renal cell carcinoma, glioblastoma multiforme and melanoma performs QC. The samples are then stored at the BPC. The BPC also processes and stores the blood samples (i.e. WBC separation, plasma, and serum).
There is a single specimen collection form, developed by the BPC, containing data elements required to track the specimens within their database as well as a list of additional items required for submission with the tumor/blood specimens such as the informed consent permission data for the tissues/blood for research and pathology report. The specimens are shipped using a common Federal Express account number.
The process for releasing specimens for analysis is currently being decided. CTEP has proposed that a committee of investigators and other experts determine the initial analyses and laboratories.
The Childhood Cancer Survivor Study (CCSS) was initiated in 1993 to study the long-term effects of cancer and its associated therapies. The CCSS is a component of the Long-Term Follow-Up Study. A collaborative, multi-institutional study funded by the National Cancer Institute, the CCSS is composed of individuals who survived five or more years after treatment for cancer, leukemia, tumor, or similar illness diagnosed during childhood or adolescence. [more...]
The CCSS cohort has been assembled through the efforts of 27 participating centers in the United States and Canada. It is coordinated through St. Jude Children's Research Hospital in Memphis, Tennessee. Other core facilities include the Statistical Center, located at the Fred Hutchinson Cancer Research Center (Seattle); the Biopathology Center (Columbus); and the Radiation Physics Center at MD Anderson Cancer Center (Houston).
The CCSS, which includes all participants in the Long-Term Follow-Up Study with a confirmed diagnosis of cancer, is a retrospectively ascertained cohort of 20,346 childhood cancer survivors diagnosed between 1970 and 1986. It also includes approximately 4,000 siblings of survivors who serve as the comparison group for the study. The Biopathology Center (BPC) is responsible for the confirmation of the diagnoses of second malignancies. Tumor tissues from participants who have developed a second malignant neoplasm are sent to the BPC where the material is reviewed.
In addition to confirmation of the diagnoses of second malignancies, the BPC has also begun to retrospectively collect paraffin tumor material to create an archive for future studies. Cores of tumor material from paraffin blocks can be used to create specific tissue microarrays. So far, materials have been accrued that would be appropriate for arrays composed of brain tumors, meningiomas, sarcomas, breast carcinomas, thyroid carcinomas, and other types of carcinomas.