Research Papers: Imaging

Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

[+] Author Affiliations
Rajan K. Bista, Shikhar Uttam, Yang Liu

University of Pittsburgh, Department of Medicine and Bioengineering, Biomedical Optical Imaging Laboratory, Pittsburgh, Pennsylvania 15232

Douglas J. Hartman, Wei Qiu, Jian Yu

University of Pittsburgh School of Medicine, Department of Pathology, Pittsburgh, Pennsylvania 15213

Lin Zhang

University of Pittsburgh Cancer Institute, Department of Pharmacology and Chemical Biology, Pittsburgh, Pennsylvania 15213

Randall E. Brand

University of Pittsburgh, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh, Pennsylvania 15232

J. Biomed. Opt. 17(6), 066014 (Jun 04, 2012). doi:10.1117/1.JBO.17.6.066014
History: Received January 10, 2012; Revised April 16, 2012; Accepted April 23, 2012
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Abstract.  The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology—spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis—ApcMin mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and evaluation of chemopreventive treatment.

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© 2012 Society of Photo-Optical Instrumentation Engineers

Citation

Rajan K. Bista ; Shikhar Uttam ; Douglas J. Hartman ; Wei Qiu ; Jian Yu, et al.
"Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model", J. Biomed. Opt. 17(6), 066014 (Jun 04, 2012). ; http://dx.doi.org/10.1117/1.JBO.17.6.066014


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