Foxp3 is a transcription factor that inhibits antitumor immune response and is expressed in regulatory T cells (Tregs). High levels of Tregs have been reported in several human cancers. This study investigates the distribution of cells positive for Foxp3, CD4 and CD8 in benign prostatic tissues and prostatic carcinoma. Tissue microarrays were constructed from radical prostatectomy specimens of 36 patients. From each patient, six cores were taken: two cores from cancer, one from benign tissue of each of the peripheral (PZ), transition (TZ) and central zones (CZ) and one from atrophy. Foxp3-, CD4- and CD8-positive cells were more common in cancer than in non-atrophic benign tissue (p < 0.01) and more common in atrophy than in non-atrophic PZ, but did not differ significantly between cancer and atrophy. Cells positive for Foxp3 and CD4 were less prevalent in CZ than in PZ and TZ. Tregs infiltrate more in prostate cancer (PC) than in benign tissue. Their presence in atrophy may have relevance for the hypothesis on atrophy as a potential precursor lesion of PC. CZ has the lowest Treg levels, and a possible role for the low rate of cancer in this zone remains to be investigated.
The evaluation of immunohistochemistry (IHC) is usually semiquantitative, and thus subject to observer variability. We analyzed the reproducibility of different IHC measures. Fifty TMA cores of prostate cancer were stained for PDX-1, a transcription factor overexpressed in the cytoplasm of prostate cancer cells. The strongest intensity was scored 0-3 and 1-3 was used for extent (1-33%, 34-66%, and 67-100%). The stains were evaluated twice by four observers: two genitourinary pathologists, and two medical doctors with no formal pathology training. Staining intensity was also measured with automated image analysis. The pathologists read the slides faster than nonpathologists (total time 88 and 178 min, respectively, p = 0.03). Mean weighted kappa for intraobserver agreement was 0.85 (range 0.81-0.89) for intensity and 0.43 (range 0.38-0.51) for extent with similar results among pathologists and nonpathologists. Mean weighted kappa for interobserver agreement was 0.80 (range 0.77-0.84) for intensity and 0.21 (range 0.11-0.26) for extent. The subjective estimations of intensity correlated with results of image analysis (r = 0.61-0.66, p < 0.001), but the correlation between observers was stronger (r = 0.75-0.81) and correlated better with Gleason grade. Thus, subjective assessment of intensity can be done with a high level of reproducibility while estimation of staining extent is less reliable. Although educated pathologists were faster, the level of pathology training is not crucial for obtaining reproducible results in the analysis of TMA-based studies.
AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool.
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