Magi-Galluzzi C, Xu X, Hlatky L, Hahnfeldt P, Kaplan I, Hsiao P, Chang C, Loda M
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Mod Pathol. 1997 Aug;10(8):839-45.
The principal mode of treatment of advanced (late stage) prostate cancer is androgen ablation. Although the response rate to hormonal ablation is high, relapse ultimately leading to death occurs in the majority of patients in remission from outgrowth of androgen-independent tumor cells. High-grade and high-stage cancers are more likely to progress to androgen independence. This study was undertaken to analyze the expression level of androgen receptor (AR) protein in prostatic carcinomas in relationship to grade and stage of disease. AR protein expression was assessed in 40 archival cases of prostate carcinoma by automated immunohistochemical techniques with standardized development times. Positive nuclei were quantitated by computer-assisted image analysis. Eighty-five percent of the prostatic carcinomas showed high levels of expression, defined as having AR present in more than 50% of the cells by light microscopy. Results of image analysis demonstrated that the variability of AR protein content per unit nuclear area increased with increasing grade (P < .03), regardless of cell size. High-grade prostatic intraepithelial neoplasia (PIN), present in 17 (42.5%) of the 40 cases, showed markedly reduced AR nuclear staining, compared with low-grade PIN or normal prostate. We show that AR content in prostate tumor cells becomes more variable with increasing Gleason score. In high-grade PIN, the in situ precursor of invasive prostate cancer, AR expression is either downregulated and/or restricted to the cytoplasm, but it is not heterogeneous. These data suggest that the heterogeneity in the expression of the receptor increases with progression of invasive prostate cancer and might in part account for a variable response to endocrine therapy.
晚期前列腺癌的主要治疗方式是雄激素去除。尽管激素去除的缓解率较高，但大多数缓解的患者最终会因雄激素非依赖性肿瘤细胞的生长而复发并导致死亡。高分级和高分期的癌症更易进展为雄激素非依赖性。本研究旨在分析前列腺癌中雄激素受体（AR）蛋白的表达水平与疾病分级和分期的关系。采用自动免疫组化技术及标准化显色时间，对40例前列腺癌存档病例的AR蛋白表达进行评估。通过计算机辅助图像分析对阳性细胞核进行定量。85%的前列腺癌显示高水平表达，即通过光学显微镜观察，超过50%的细胞中存在AR。图像分析结果表明，无论细胞大小，单位核面积内AR蛋白含量的变异性随分级增加而增大（P <.03）。40例病例中有17例（42.5%）存在高级别前列腺上皮内瘤变（PIN），与低级别PIN或正常前列腺相比，其AR核染色明显减少。我们发现，随着Gleason评分增加，前列腺肿瘤细胞中的AR含量变异性更大。在高级别PIN（浸润性前列腺癌的原位前体）中，AR表达下调和/或局限于细胞质，但并非异质性表达。这些数据表明，随着浸润性前列腺癌进展，受体表达的异质性增加，这可能部分解释了内分泌治疗反应的差异。
