Bosl G J, Ilson D H, Rodriguez E, Motzer R J, Reuter V E, Chaganti R S
Memorial Hospital, New York, NY 10021.
J Natl Cancer Inst. 1994 Mar 2;86(5):349-55. doi: 10.1093/jnci/86.5.349.
Germ cell tumors in men are curable at all stages and are among the most sensitive of all cancers to chemotherapy. An isochromosome of the short arm of chromosome 12, i(12p), has been reported to be a frequent marker of these tumors and to have diagnostic and prognostic significance.
We evaluated the possible association between this cytogenetic marker and clinical outcome for men with germ cell tumors.
One hundred seventy-eight germ cell tumor samples from 150 men were studied using conventional and molecular cytogenetic techniques. Of these samples, 171 were evaluable. Patient characteristics, disease stage, treatment outcome, and disease status were correlated with the observed cytogenetic changes. In addition, 28 biopsy specimens obtained from 28 patients with tumors of uncertain histogenesis were evaluated to determine whether the presence of i(12p) could serve as a diagnostic marker of a germ cell origin for these tumors.
Of the 171 evaluable tumor accessions, 101 (59%) yielded abnormal karyotypes. i(12p) was determined to be present in 79 of the 101 (79%) abnormal karyotypes, which were derived from all cell types and primary sites. An abnormal karyotype was more frequently obtained from nonseminomatous tumors (91/137 [81%]) than from seminomas (10/34 [30%] [P < .001]). Tumors resulting in a cytogenetic failure were more likely to respond completely to chemotherapy than tumors with an abnormal karyotype (P = .004). i(12)p copy number was not associated with response or survival. Fluorescence in situ hybridization using a chromosome 12 centromere-specific probe detected i(12p) in 47 of 47 tumors (100%) already shown to have i(12p) by cytogenetic analysis and in 13 of 49 tumors (27%) exhibiting either an abnormal karyotype or a cytogenetic failure. One or more copies of i(12p), excess 12p copy number, or a deletion on the long arm of chromosome 12 was found in seven of 28 (25%) midline tumors of uncertain histogenesis, thus establishing a diagnosis of a germ cell tumor in these patients. One partial and five complete responses were observed in these seven patients. Only two partial responses were seen in the 17 patients who had no detectable germ cell tumor-related cytogenetic marker (P = .009).
i(12p) is a highly nonrandom chromosomal marker seen in about 80% of male germ cell tumors with evaluable cytogenetic abnormalities. The presence of this isochromosome has diagnostic and possibly prognostic importance for patients with these tumors.
Cytogenetic studies of germ cell tumors in prospective clinical treatment trials are warranted to define more precisely the relationship between histologic subtype, serum tumor marker production, and prognosis.
男性生殖细胞肿瘤在所有阶段均可治愈，是所有癌症中对化疗最敏感的癌症之一。据报道，12号染色体短臂等臂染色体i(12p)是这些肿瘤的常见标志物，具有诊断和预后意义。
我们评估了这种细胞遗传学标志物与男性生殖细胞肿瘤临床结局之间的可能关联。
使用传统和分子细胞遗传学技术研究了150名男性的178份生殖细胞肿瘤样本。其中171份样本可评估。将患者特征、疾病分期、治疗结局和疾病状态与观察到的细胞遗传学变化进行关联分析。此外，对28例组织发生不明确的肿瘤患者的活检标本进行评估，以确定i(12p)的存在是否可作为这些肿瘤生殖细胞起源的诊断标志物。
在171份可评估的肿瘤样本中，101份（59%）产生了异常核型。在101份异常核型中的79份（79%）中检测到i(12p)，这些异常核型来自所有细胞类型和原发部位。非精原细胞瘤（91/137 [81%]）比精原细胞瘤（10/34 [30%] [P <.001]）更常出现异常核型。导致细胞遗传学分析失败的肿瘤比具有异常核型的肿瘤更有可能对化疗完全缓解（P =.004）。i(12)p拷贝数与缓解或生存无关。使用12号染色体着丝粒特异性探针的荧光原位杂交在细胞遗传学分析已显示有i(12p)的47例肿瘤中的47例（100%）以及49例表现出异常核型或细胞遗传学分析失败的肿瘤中的13例（27%）中检测到i(12p)。在28例组织发生不明确的中线肿瘤中的7例（25%）中发现了一个或多个i(12p)拷贝、12p拷贝数过多或12号染色体长臂缺失，从而确定这些患者为生殖细胞肿瘤。这7例患者中观察到1例部分缓解和5例完全缓解。在17例未检测到生殖细胞肿瘤相关细胞遗传学标志物的患者中仅观察到2例部分缓解（P =.009）。
i(12p)是约80%具有可评估细胞遗传学异常的男性生殖细胞肿瘤中高度非随机的染色体标志物。这种等臂染色体的存在对这些肿瘤患者具有诊断和可能的预后意义。
在前瞻性临床治疗试验中对生殖细胞肿瘤进行细胞遗传学研究，以更精确地确定组织学亚型、血清肿瘤标志物产生与预后之间的关系是必要的。
