Abstract. The gold standard in histopathology relies on manual investigation of stained tissue biopsies. A sensitive and quantitative method for in situ tissue specimen inspection is highly desirable, as it would allow early disease diagnosis and automatic screening. Here we demonstrate that quantitative phase imaging of entire unstained biopsies has the potential to fulfill this requirement. Our data indicates that the refractive index distribution of histopathology slides, which contains information about the molecular scale organization of tissue, reveals prostate tumors and breast calcifications. These optical maps report on subtle, nanoscale morphological properties of tissues and cells that cannot be recovered by common stains, including hematoxylin and eosin. We found that cancer progression significantly alters the tissue organization, as exhibited by consistently higher refractive index variance in prostate tumors versus normal regions. Furthermore, using the quantitative phase information, we obtained the spatially resolved scattering mean free path and anisotropy factor g for entire biopsies and demonstrated their direct correlation with tumor presence. In essence, our results show that the tissue refractive index reports on the nanoscale tissue architecture and, in principle, can be used as an intrinsic marker for cancer diagnosis. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

The effects of alcohol consumption on various T lymphocyte subset functions and on the degree of susceptibility of peripheral blood mononuclear cells (PBMC) to human immunodeficiency virus (HIV) type 1 infection and replication in vitro were investigated. PBMC from 60 HIV-1-seronegative healthy volunteers were studied before and after ingestion of alcohol beverages. After alcohol consumption, there was significantly increased HIV-1 replication (P < .001) in PBMC, as determined by HIV-1 p24 antigen levels in the culture supernatants, than in cultures obtained before alcohol ingestion. There was a decreased ability of lymphocytes, obtained after alcohol consumption, to produce interleukin-2 and soluble immune response suppressor activity after stimulation with concanavalin A. The data show that alcohol ingestion increases HIV-1 replication in human PBMC infected with HIV-1 in cell culture. This may be due to alcohol-induced functional impairment of various subsets of lymphocytes in the peripheral blood. Thus, HIV-1 replication may be augmented by alcohol in HIV-1-infected individuals, and alcohol intake may increase an individual's risk for acquiring HIV-1 infection.

The standard practice in histopathology of breast cancers is to examine a hematoxylin and eosin (H&E) stained tissue biopsy under a microscope to diagnose whether a lesion is benign or malignant. This determination is made based on a manual, qualitative inspection, making it subject to investigator bias and resulting in low throughput. Hence, a quantitative, label-free, and high-throughput diagnosis method is highly desirable. We present here preliminary results showing the potential of quantitative phase imaging for breast cancer screening and help with differential diagnosis. We generated phase maps of unstained breast tissue biopsies using spatial light interference microscopy (SLIM). As a first step toward quantitative diagnosis based on SLIM, we carried out a qualitative evaluation of our label-free images. These images were shown to two pathologists who classified each case as either benign or malignant. This diagnosis was then compared against the diagnosis of the two pathologists on corresponding H&E stained tissue images and the number of agreements were counted. The agreement between SLIM and H&E based diagnosis was 88% for the first pathologist and 87% for the second. Our results demonstrate the potential and promise of SLIM for quantitative, label-free, and high-throughput diagnosis.

Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.

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We report experimental evidence of correlation-induced spectral changes in biological tissues. The overall spectral shift in our transmission measurements is to the red and the mean wavelength of the original spectrum is up 10% larger. These results indicate that the spectral changes due to elastic scattering are significant and likely to hinder all spectroscopic measurements based on the inelastic (i.e., emission and absorption) interaction between light and tissues. Thus, simultaneous morphology and spectral measurements are required for accurate measurements spectroscopic information.

In-clinic validation of predictive technologies will help the clinician adopt truly beneficial technologies and avoid the adoption of technologies which provide no significant benefit to their local patient population. For this task, sequential methods offer clear advantages.