Takahashi S, Alcaraz A, Brown J A, Borell T J, Herath J F, Bergstralh E J, Lieber M M, Jenkins R B
Department of Urology and Laboratory Medicine and Pathology and Section of Biostatistics, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Clin Cancer Res. 1996 Jan;2(1):137-45.
In an attempt to identify new prognostic markers, we performed fluorescence in situ hybridization (FISH) ploidy analysis of tumor tissue from patients with a targeted stage and histological grade of prostate carcinoma. We identified all 227 patients from the Mayo Clinic radical prostatectomy data base who had a high histological grade pathological stage C (pT3N0M0) tumor removed between 1966 and 1987. After histological review of the paraffin-embedded specimen blocks, 181 cases were suitable for FISH analysis using chromosome enumeration probes for chromosomes 7, 8, 10, 12, X, and Y. FISH detected 80 (44%) diploid, 22 (12%) tetraploid, and 79 (44%) aneuploid tumors. The common aneusomies were of chromosomes 7 and 8, which were present in 51 (28%) and 46 (25%) tumors, respectively. Aneusomies of chromosomes 10, 12, X, and Y were observed in 11 (6%), 15 (8%) 12 (7%) and 16 (9%) tumors, respectively. FISH aneuploid tumors showed a trend of more frequent systemic prostate cancer progression than nonaneuploid tumors (P = 0.060). For individual chromosome anomalies, gains of chromosome 8, aneusomy of chromosome 8, and aneusomy of chromosome Y correlated highly with systemic cancer progression (P = 0.006, 0.013, and 0.021, respectively). Gains of chromosome Y and aneusomy of chromosome Y were associated with an increased prostate cancer death rate (P < 0.001 for both). Multivariate analysis showed that gains of chromosome 8 and aneusomy of chromosome Y were significant independent "predictors" of systemic cancer progression (P = 0.008) and cancer death (P < 0.001), respectively. These results demonstrate that aneuploidy and specific aneusomies detected by FISH are potential markers for a poor prognosis in histological high-grade pathological stage C (pT3N0M0) prostate carcinoma.
为了确定新的预后标志物，我们对目标分期和组织学分级的前列腺癌患者的肿瘤组织进行了荧光原位杂交（FISH）倍性分析。我们从梅奥诊所根治性前列腺切除术数据库中识别出所有227例患者，他们在1966年至1987年间切除了高组织学分级的病理分期为C（pT3N0M0）的肿瘤。在对石蜡包埋标本块进行组织学复查后，181例病例适合使用针对7号、8号、10号、12号染色体、X染色体和Y染色体的染色体计数探针进行FISH分析。FISH检测到80例（44%）二倍体肿瘤、22例（12%）四倍体肿瘤和79例（44%）非整倍体肿瘤。常见的非整倍体是7号和8号染色体，分别存在于51例（28%）和46例（25%）肿瘤中。10号、12号、X染色体和Y染色体的非整倍体分别在11例（6%）、15例（8%）、12例（7%）和16例（9%）肿瘤中观察到。FISH检测到的非整倍体肿瘤比非非整倍体肿瘤显示出更频繁的系统性前列腺癌进展趋势（P = 0.060）。对于单个染色体异常，8号染色体的增加、8号染色体的非整倍体和Y染色体的非整倍体与系统性癌症进展高度相关（分别为P = 0.006、0.013和0.021）。Y染色体的增加和Y染色体的非整倍体与前列腺癌死亡率增加相关（两者P均<0.001）。多变量分析表明，8号染色体的增加和Y染色体的非整倍体分别是系统性癌症进展（P = 0.008）和癌症死亡（P < 0.001）的显著独立“预测因子”。这些结果表明，FISH检测到的非整倍体和特定的非整倍体是组织学高分级病理分期为C（pT3N0M0）前列腺癌预后不良的潜在标志物。
