The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial Pathology Tissue Resource

Abstract

Background Pathology tissue specimens with associated epidemiological and clinical data are valuable for cancer research. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial undertook a large-scale effort to create a public resource of pathology tissues from PLCO participants who developed a cancer during the trial. Methods Formalin-Fixed Paraffin-Embedded (FFPE) tissue blocks were obtained from pathology laboratories on a loan basis for central processing of tissue microarrays, with additional free-standing tissue cores collected for nucleic acid extraction. Results Pathology tissue specimens have been obtained for prostate cancer (n=1,052), lung cancer (n=434), colorectal cancer (n=675) and adenoma (n=658), ovarian cancer and borderline tumors (n=212), breast cancer (n=870) and bladder cancer (n=204). The process of creating this resource was complex, involving multi-disciplinary teams with expertise in pathology, epidemiology, information technology, project management and specialized laboratories. Conclusions Creating the PLCO tissue resource required a multi-step process including obtaining medical records and contacting pathology departments where pathology materials were stored after obtaining necessary patient consent and authorization. The potential to link tissue biomarkers to prospectively collected epidemiological information, screening and clinical data, and matched blood or buccal samples offers valuable opportunities to study etiologic heterogeneity, mechanisms of carcinogenesis and biomarkers for early detection and prognosis. Impact The methods and protocols developed for this effort, and the detailed description of this resource provided here will be useful for those seeking to use PLCO pathology tissue specimens for their research and may also inform future tissue collection efforts in other settings.

Genetically predicted circulating protein biomarkers and ovarian cancer risk

“…A major strength of the current analysis was the ability to appraise the roles of over 1,300 proteins. A vital next step in assessing the role of the plasma proteome in EOC risk and validating our findings will involve directly measuring the 26 proteins shortlisted by our study in EOC case and control sample collections that have pre-diagnostic and longitudinal follow-up biospecimens available such as the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial [33]. The pleiotropic associations observed at the 9q34.2 locus where eight of the ten SNPs associated with plasma protein levels were also associated with other traits leaves open the possibility that some of these traits, rather than the protein levels, may underlie the association with EOC risk.…”

The BC Generations Project as a Tumor Tissue Resource for Cancer Research

“…Our overall tumor sample acquisition rate (87%) is higher than that reported by previous studies. For example, the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial only reported a sample retrieval success rate of 47% [ 7 ], with the Nurses’ Health Study reporting success rates of 70–80% [ 8 ].…”

“…Various large-scale cohort studies from around the world have established tumor tissue repositories to support innovative research [ 6 , 7 , 8 , 9 ]. Currently, there are no cohort studies in Canada with similarly available resources.…”

Weighting estimation in the cause‐specific Cox regression with partially missing causes of failure

“…Molecular pathological epidemiology, which has recently received considerable attention, aims to elucidate specific relationships between putative etiologic factors and cellular molecular alterations. In particular, the molecularly defined subtypes of neoplastic diseases, including endometrial cancer, 3 colorectal cancer (CRC), 4,5 lung cancer, 6 and breast cancer, 7 are often associated with specific risk factors, emphasizing the importance of characterizing critical molecular alterations in tumor cells. In CRC, multiple biomarkers have been used to address the complexity of the disease and define tumor subtypes 8,9 .…”