IR spectroscopy with multivariate analysis potentially facilitates the segregation of different types of prostate cell

¹ Lancaster University
² Daresbury Laboratories
³ Lancashire Teaching Hospitals Trust

^* To whom correspondence should be addressed. E-mail: f.martin{at}lancaster.ac.uk.

Submitted on November 7, 2005
Revised on December 13, 2005
Accepted on 7 February 2006

	Abstract

The prostate gland is conventionally divided into zones or regions. This morphology is of clinical significance as prostate cancer (CaP) occurs mainly in the peripheral zone (PZ). We obtained tissue sets consisting of paraffin-embedded blocks of cancer-free transition zone (TZ) and PZ, and adjacent CaP from patients (n=6) who had undergone radical retropubic prostatectomy; a seventh tissue set of snap-frozen PZ and TZ was obtained from a CaP-free gland removed following radical cystoprostatectomy. Paraffin-embedded tissue slices were sectioned (10-µm thick) and mounted on suitable windows to facilitate IR spectra acquisition before being de-waxed and air-dried; cryosections were dessicated on BaF₂ windows. Spectra were collected employing synchrotron Fourier-transform infrared (FTIR) microspectroscopy in transmission mode or attenuated total reflection-FTIR (ATR) spectroscopy. Epithelial-cell and stromal IR spectra were subjected to principal component analysis to determine whether wavenumber-absorbance relationships expressed as single points in "hyperspace" might on the basis of multivariate distance reveal biophysical differences between cells in situ in different tissue regions. Following spectroscopic analysis, plotted clusters and their loadings curves highlighted marked variation in the spectral region containing DNA/RNA bands (1,490 cm^-1 to 1,000 cm^-1). By interrogating the intrinsic dimensionality of IR spectra in this small cohort sample, we found that TZ epithelial cells appeared to align more closely with those of CaP while exhibiting marked structural differences compared to PZ epithelium. IR spectra of PZ stroma also suggested that these cells are structurally more different to CaP than those located in the TZ. Because the PZ exhibits a higher occurrence of CaP, other factors (e.g. hormone exposure) may modulate the growth kinetics of initiated epithelial cells in this region. The results of this pilot study surprisingly indicate that TZ epithelial cells are more likely to exhibit what may be a susceptibility-to-adenocarcinoma spectral signature. Thus, IR spectroscopy on its own may not be sufficient to identify pre-malignant prostate epithelial cells most likely to progress to CaP.

Key Words: Cluster vector, IR spectroscopy, Peripheral zone, Principal component analysis, Prostate cancer, Transition zone

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