Quantitation and morphometric analysis of tumors by image analysis

Digital image analysis provides objective measurements of tissue and cell analytes previously interpreted subjectively. Both analyte concentration determination and morphometric analyses are possible. Calibration of the instrument and the use of standards and controls are essential for precise and reproducible quantitation of the analyte. Multi-tissue blocks ensure reproducible staining of the batch in quantitative immunohistochemical assays such as breast cancer estrogen and progesterone receptors. These multi-tissue blocks can be shared among laboratories to reduce interlaboratory variation and to objectively quantitate estrogen and progesterone receptors in clinical trials. In colon carcinoma, p53 can be quantitated objectively by image analysis. In prostate carcinoma, morphometric analysis of nuclear shape, nuclear roundness factor, and variations in nuclear size are objective measurements which constitute the pathologist's nuclear grade. Developments in instrumentation have now made it possible to combine analyte determination (such as DNA ploidy) and morphologic analysis of tumors, a diagnostic improvement over either method alone. A study employing image analysis to detect and quantitate androgen receptors and p53 in formalin-fixed, paraffin-embedded prostate cancer biopsies is underway to determine the utility of androgen receptors in predicting response to hormonal therapy. Histopathological features such as nuclear size, shape, and pleomorphism must be converted to image features such as area, shape factor, and variance of the area; this feature vector must be correlated with the pathologist's expert opinion or diagnosis. Other applications of image analysis include quantitation of immunofluorescent assays such as anti-nuclear antigen or anti-cytoplasmic nuclear antigen. Fluorescent image analysis provides more precision and greater reproducibility, as well as reduced test costs.(ABSTRACT TRUNCATED AT 250 WORDS)