Breast Cancer Research and Treatment

, Volume 135, Issue 1, pp 115–124 | Cite as

Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer

  • Rajan K. Bista
  • Pin Wang
  • Rohit Bhargava
  • Shikhar Uttam
  • Douglas J. Hartman
  • Randall E. Brand
  • Yang Liu
Preclinical Study


Accurate detection of breast malignancy from histologically normal cells (“field effect”) has significant clinical implications in a broad base of breast cancer management, such as high-risk lesion management, personalized risk assessment, breast tumor recurrence, and tumor margin management. More accurate and clinically applicable tools to detect markers characteristic of breast cancer “field effect” that are able to guide the clinical management are urgently needed. We have recently developed a novel optical microscope, spatial-domain low-coherence quantitative phase microscopy, which extracts the nanoscale structural characteristics of cell nuclei (i.e., nuclear nano-morphology markers), using standard histology slides. In this proof-of-concept study, we present the use of these highly sensitive nuclear nano-morphology markers to identify breast malignancy from histologically normal cells. We investigated the nano-morphology markers from 154 patients with a broad spectrum of breast pathology entities, including normal breast tissue, non-proliferative benign lesions, proliferative lesions (without and with atypia), “malignant-adjacent” normal tissue, and invasive carcinoma. Our results show that the nuclear nano-morphology markers of “malignant-adjacent” normal tissue can detect the presence of invasive breast carcinoma with high accuracy and do not reflect normal aging. Further, we found that a progressive change in nuclear nano-morphology markers that parallel breast cancer risk, suggesting its potential use for risk stratification. These novel nano-morphology markers that detect breast cancerous changes from nanoscale structural characteristics of histologically normal cells could potentially benefit the diagnosis, risk assessment, prognosis, prevention, and treatment of breast cancer.


Field effect Nanoscale structure Phase microscopy Nuclear nano-morphology markers 



This study was supported by research grants from National Institute of Health (R21CA152935) and Wallace H. Coulter foundation. P. W. acknowledges the support from National Energy Technology Laboratory Research Participation Program sponsored by the U.S. Department of Energy and administered by the Oak Ridge Institute for Science and Education.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10549_2012_2125_MOESM1_ESM.doc (150 kb)
Supplementary material 1 (DOC 150 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Rajan K. Bista
    • 1
  • Pin Wang
    • 1
  • Rohit Bhargava
    • 2
  • Shikhar Uttam
    • 1
  • Douglas J. Hartman
    • 3
  • Randall E. Brand
    • 1
  • Yang Liu
    • 1
    • 4
    • 5
  1. 1.Division of Gastroenterology, Hepatology and Nutrition, Department of MedicineUniversity of PittsburghPittsburghUSA
  2. 2.Department of Pathology, Magee-Womens HospitalUniversity of Pittsburgh Medical CenterPittsburghUSA
  3. 3.Department of PathologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of BioengineeringUniversity of PittsburghPittsburghUSA
  5. 5.Departments of Medicine and BioengineeringUniversity of PittsburghPittsburghUSA

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