Abstract:
Prostate cancer is a biologically heterogenous disease with considerable variation in
clinical aggressiveness. Gleason grade, the universally accepted method for
classification of prostate cancer, is subjective and gives limited predictive information
regarding prostate cancer progression. There is a clinical need for an objective, reliable
tool to help pathologists improve current prostate tissue analysis methods and better
assess the malignant potential of prostate tumours. Fourier Transform Infrared (FTIR)
microspectroscopy is a powerful bioanalytical technique that uses infrared light to
interrogate biological tissue. The studies detailed in this thesis examine the ability of
FTIR combined with multivariate analysis to discriminate between benign,
premalignant and malignant prostate pathology in snap frozen, paraffinated and
deparaffinated tissue.
Prostate tissue was collected during and after urological procedures performed between
2005 and 2008. The tissue was analysed utilising a bench top FTIR system in point and
image mapping modes. The histology under interrogation was identified by a uro-
pathologist. Multivariate analysis was applied to the spectral dataset obtained. FTIR
performance was evaluated.
FTIR was able to reproducibly discriminate between benign and malignant prostate
tissue in a pilot study. Cross validated diagnostic algorithms, constructed from the
spectral dataset in this experiment, achieved sensitivities and specificities of 95% and
89% respectively.
FTIR analysis of transverse paraffinated and deparaffinated radical prostatectomy
sections achieved good differentiation of the benign, premalignant and malignant
pathology groups. However the performance of diagnostic algorithms constructed from
this dataset under cross validation was poor.
The work in this thesis illustrates the potential of FTIR to provide an objective method
to assist the pathologist in the assessment of prostate samples. The limitations of the
technique and directions for future work are presented.