Nanocytological Field Carcinogenesis Detection to Mitigate Overdiagnosis of Prostate Cancer: A Proof of Concept Study

To determine whether nano-architectural interrogation of prostate field carcinogenesis can be used to predict prognosis in patients with early stage (Gleason 6) prostate cancer (PCa), which is mostly indolent but frequently unnecessarily treated. We previously developed partial wave spectroscopic mi...

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Published in:PloS one Vol. 10; no. 2; p. e0115999
Main Authors: Roy, Hemant K., Brendler, Charles B., Subramanian, Hariharan, Zhang, Di, Maneval, Charles, Chandler, John, Bowen, Leah, Kaul, Karen L., Helfand, Brian T., Wang, Chi-Hsiung, Quinn, Margo, Petkewicz, Jacqueline, Paterakos, Michael, Backman, Vadim
Format: Journal Article
Language:English
Published: United States Public Library of Science 23.02.2015
Public Library of Science (PLoS)
Subjects:
Aged
Biomedical engineering
Cancer
Cancer research
Carcinogenesis
Carcinogenesis - pathology
Carcinogens
Case-Control Studies
Cellular structure
Demographics
Disease control
Early Detection of Cancer
Engineering
Epithelial cells
Esophagus
Gene expression
Heterogeneity
Humans
Interrogation
Male
Mathematical morphology
Medical diagnosis
Medical Overuse
Medical prognosis
Medical screening
Microscopy
Middle Aged
Mucosa
Neoplasm Grading
Prognosis
Prostate - pathology
Prostate cancer
Prostatic Neoplasms - diagnosis
Prostatic Neoplasms - pathology
Questioning
Smoking
Spatial heterogeneity
Surgery
Surveillance
United States > US
Illinois
ISSN:1932-6203, 1932-6203
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Description
Summary:To determine whether nano-architectural interrogation of prostate field carcinogenesis can be used to predict prognosis in patients with early stage (Gleason 6) prostate cancer (PCa), which is mostly indolent but frequently unnecessarily treated. We previously developed partial wave spectroscopic microscopy (PWS) that enables quantification of the nanoscale intracellular architecture (20-200 nm length scale) with remarkable accuracy. We adapted this technique to assess prostate needle core biopsies in a case control study from men with Gleason 6 disease who either progressed (n = 20) or remained indolent (n = 18) over a ~3 year follow up. We measured the parameter disorder strength (Ld) characterizing the spatial heterogeneity of the nanoscale cellular structure and nuclear morphology from the microscopically normal mucosa ~150 histologically normal epithelial cells. There was a profound increase in nano-architectural disorder between progressors and non-progressors. Indeed, the Ld from future progressors was dramatically increased when compared to future non-progressors (1±0.065 versus 1.30±0.0614, respectively p = 0.002). The area under the receiver operator characteristic curve (AUC) was 0.79, yielding a sensitivity of 88% and specificity of 72% for discriminating between progressors and non-progressors. This was not confounded by demographic factors (age, smoking status, race, obesity), thus supporting the robustness of the approach. We demonstrate, for the first time, that nano-architectural alterations occur in prostate cancer field carcinogenesis and can be exploited to predict prognosis of early stage PCa. This approach has promise in addressing the clinically vexing dilemma of management of Gleason 6 PCa and may provide a paradigm for dealing with the larger issue of cancer overdiagnosis.
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These authors contributed equally to this work.
Competing Interests: Drs. Roy, Subramanian and Backman are co-founders of Nanocytomics LLC and managed by the conflict of interest committees of Boston University and Northwestern University. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: HR CB HS KK BH VB. Performed the experiments: HS DZ CM JC LB KK BH MQ JP MP. Analyzed the data: HS DZ CM JC LB CW. Contributed reagents/materials/analysis tools: HS DZ CM JC LB CW KK. Wrote the paper: HR CB HS VB.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0115999