Abstract
Background/Objectives:Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER), which are the oldest, extend back only to the 1970s.Methods:To extend scant knowledge about the feasibility of obtaining long-term data on tumor biomarkers, we randomly selected 60 breast cancer cases (10 per decade) diagnosed between 1947–2009 among women members of the Kaiser Permanente Northern California health plan to obtain and analyze their formalin-fixed paraffin-embedded (FFPE) tumor specimens. For each tumor specimen, we created duplicate tissue microarrays for analysis.Results:We located tumor blocks and pathology reports for 50 of the 60 cases (83%), from which we randomly sampled 5 cases per decade for biomarker analysis (n=30). All 30 cases displayed excellent morphology and exhibited biomarkers compatible with histologic type and grade. Test–retest reliability was also excellent: 100% for ER; 97% for human epidermal growth factor receptor 2 and epidermal growth factor receptor; 93% for progesterone receptor and cytokeratin 5/6; and 90% for Ki67 and molecular phenotype; the kappa statistic was excellent (>0.9) for 4 of the 7 biomarkers, strong (0.6–0.8) for 2, and fair for only 1 (owing to low prevalence).Conclusions:These results indicate immunostaining for biomarkers commonly used to evaluate breast cancer biology and assign surrogate molecular phenotypes can reliably be employed on archival FFPE specimens up to 60 years old.
Highlights
Determining long-term trends in tumor biomarkers is crucial for understanding what aspects of tumor biology are amenable to change
We analyzed formalin-fixed paraffin-embedded (FFPE) specimens obtained from women diagnosed with invasive breast cancer who were members of Kaiser Permanente, Northern California (KPNC; institutional review board approval: Harvard School of Public Health/#CR-20929–02; KPNC/ #CN-13LHabe-03-H)
KPNC is an integrated healthcare delivery system established in the 1940s16 and whose cancer registry dates back to 1947.17 Since its inception as a health plan for workers employed in World War II shipyards, KPNC’s membership has ranged from working class to professional and has mirrored the well-known diversity of the San Francisco Bay Area and Central Valley, comprised of white, black, Hispanic, Asian and Pacific Islander, and American Indian populations.[17,18]
Summary
Determining long-term trends in tumor biomarkers is crucial for understanding what aspects of tumor biology are amenable to change. Contributing to the lack of such historical data is the relatively recent development of most currently used assays: in the case of breast cancer, for example, one of the first such assays, for ER, became available only in the 1970s,12 and characterization of molecular phenotypes is an innovation of the 21st century CE.[13] We conducted a novel feasibility study, including assessment of test–retest reliability, for a series of breast cancer cases spanning 6 decades (1947–2009).
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