Immunohistochemical analysis of radical prostatectomy specimens after 8 months of neoadjuvant hormonal therapy

Neoadjuvant hormone therapy (NHT) prior to radical prostatectomy (RP) resul ts in residual foci of atrophic glands, which can be difficult to identify with hematoxylin-eosin staining, raising the possibility that the low posit ive-margin rates are an artifact of pathologic understaging, The purpose of this study was to evaluate changes in prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), as well as proliferation marker Ki-67 and Bcl-2 oncoprotein, by immunostaining after 8 months of NHT, Twenty-nine me n with clinically confined prostate cancer who received 8 months of NHT and had both pretreatment biopsy and RP specimens obtained at Vancouver Hospit al constituted the treatment group. The control group consisted of 23 RP sp ecimens from patients not receiving NHT, Sections were stained with antibod ies against PSA, PAP, proliferation marker Ki-67, and the antiapoptosis pro tein Bcl-2, The PSA and PAP immunostaining were graded for percentage of po sitive tumor cells and intensity of staining, while Ki-67 and Bcl-2 stainin g was graded according to the percentage of positive tumor cells. Absent or low percentage-positive PSA and PAP staining was observed in 40% to 50% of the NHT-treated RP specimens but none of the needle biopsy or untreated co ntrol RP specimens, Low-intensity PSA and PAP staining was detected only in RP specimens after NHT treatment, and then in only 20% of cases. Low or ab sent Ki-67 staining was noted in 78% of the NHT-treated RP specimens, compa red with only 13% of the matched pre-NHT needle biopsies and 26% of untreat ed RP specimens. The percentage of specimens with high (>5%) Ki-67 staining decreased from 37% in the pre-NHT needle biopsies to 8% in the NHT-treated RP specimens. Bcl-2 staining increased after treatment with NHT, with 20% of the needle biopsies having high (>5%) Bcl-2 staining compared with 53% o f the NHT-treated RP specimens. The frequency of low Bcl-2 staining (<1%) d ecreased from 53% in the pre-NHT needle biopsies to 27% in the NHT-treated RP specimens. Although PAP and PSA staining decreased after NHT, both marke rs remain sufficiently positive to be used as epithelial markers to help de tect residual foci of prostate cancer that are difficult to identify on H&E -stained slides after NHT. Increased Bcl-2 after NHT, even in early-stage d isease, is consistent with its role in the prevention of apoptosis and prog ression to androgen independence. Low levels of Ki-67 staining indicates a low probability of proliferation and outgrowth of androgen-independent clon es after 8 months of NHT.