Departments of Gynecology, Institute of Pathology, Martini-Clinic, Prostate Cancer Center, University Medical Center, Hamburg, Germany.
Clin Cancer Res. 2010 Jan 1;16(1):56-64. doi: 10.1158/1078-0432.CCR-09-1423. Epub 2009 Dec 22.
Deletions of 8p and gains of 8q belong to the most frequent cytogenetic alterations in prostate cancer. The target genes of these alterations and their biological significance are unknown.
To determine the relationship between chromosome 8 changes, and prostate cancer phenotype and prognosis, a set of 1.954 fully annotated prostate cancers were analyzed in a tissue microarray format by fluorescence in situ hybridization.
Both 8p deletions and 8q gains increased in number during different stages of prostate cancer progression. 8p deletions/8q gains were found in 26.1%/4.8% of 1,239 pT(2) cancers, 38.5%/9.8% of 379 pT(3a) cancers, 43.5%/8.9% of 237 pT(3b) cancers, 40.7%/14.8% of 27 pT(4) cancers, 39.1%/34.8% of 23 nodal metastases, 51.9%/33.3% of 27 bone metastases, and 45.5%/59.9% of 22 hormone refractory cancers (P < 0.0001 each). Both 8p deletions and 8q gains were also significantly associated with high Gleason grade and with each other (P < 0.0001 each). In primary tumors, 8p deletions were seen in only 27.3% of 1,882 cancers without 8q gain but in 57.4% of 122 tumors with 8q gain (P < 0.0001). Among cancers treated with radical prostatectomy, 8p deletions (P = 0.003) and 8q gains (P = 0.02) were associated with biochemical tumor recurrence. However, multivariate analysis (including prostate-specific antigen, pT/pN stage, Gleason score, and surgical margin status) did not reveal any statistically independent effect of 8p or 8q alterations on biochemical tumor recurrence.
8p deletions and 8q gains are relatively rare in early stage prostate cancer but often develop during tumor progression. The prognostic effect does not seem to be strong enough to warrant clinical application.
8p 缺失和 8q 获得属于前列腺癌中最常见的细胞遗传学改变。这些改变的靶基因及其生物学意义尚不清楚。
为了确定染色体 8 改变与前列腺癌表型和预后的关系，我们使用荧光原位杂交技术，在组织微阵列中分析了一组 1954 个完全注释的前列腺癌。
在前列腺癌进展的不同阶段，8p 缺失和 8q 增益的数量都增加了。8p 缺失/8q 增益在 1239 例 pT(2)癌症、379 例 pT(3a)癌症、237 例 pT(3b)癌症、27 例 pT(4)癌症、23 例淋巴结转移、27 例骨转移和 22 例激素难治性癌症中分别发现 26.1%/4.8%、38.5%/9.8%、43.5%/8.9%、40.7%/14.8%、39.1%/34.8%、51.9%/33.3%和 45.5%/59.9%（均 P < 0.0001）。8p 缺失和 8q 增益也与高 Gleason 分级显著相关（均 P < 0.0001）。在原发性肿瘤中，1882 例无 8q 增益的癌症中仅 27.3%有 8p 缺失，但 122 例有 8q 增益的癌症中 57.4%有 8p 缺失（P < 0.0001）。在接受根治性前列腺切除术治疗的癌症中，8p 缺失（P = 0.003）和 8q 增益（P = 0.02）与生化肿瘤复发相关。然而，多变量分析（包括前列腺特异性抗原、pT/pN 分期、Gleason 评分和手术切缘状态）并未显示 8p 或 8q 改变对生化肿瘤复发有任何统计学上的独立影响。
8p 缺失和 8q 获得在早期前列腺癌中相对少见，但在肿瘤进展过程中常发生。预后效果似乎不足以证明其具有临床应用价值。
