Almefty Kaith K, Pravdenkova Svetlana, Sawyer Jeffrey, Al-Mefty Ossama
Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
J Neurosurg. 2009 Apr;110(4):715-24. doi: 10.3171/2008.9.JNS08285.
Cytogenetic studies of chordomas are scarce and show multiple changes involving different chromosomes. These abnormalities are implicated in the pathogenesis of chordoma, but the clinical significance of these changes is yet to be determined. In this study, the authors discuss the cytogenetic changes in a large series of skull base chordomas with long-term follow-up and focus on the impact of these changes on the prognosis, progression, and management of the disease.
The karyotypes of chordomas in 64 patients (36 men and 28 women) were studied in relation to survival and recurrence or progression over a mean follow-up period of 48 +/- 37.5 months. The standard G-banding technique was used for karyotype analysis. Statistical analysis was performed with the Fisher exact test and ORs, and Kaplan-Meier curves were generated for survival and recurrence/progression of disease.
Seventy-four percent of de novo chordomas had normal karyotypes and a 3% recurrence rate; there was a 45% recurrence rate in de novo tumors with abnormal karyotypes (p < 0.01). Recurrent tumors were associated with a high incidence of abnormal karyotype (75%). The OR for recurrence in lesions with an abnormal versus a normal karyotype was 12. Aberrations in chromosomes 3, 4, 12, 13, and 14 were associated with frequent recurrence and decreased survival time. Ninety-five percent of cases with progression involved chromosome 3 and/or 13. The median survival time was 4 months when both of these chromosomes had aberrations (p = 0.02).
Chordomas with normal karyotypes were associated with a low rate of recurrence and a long patient survival, and recurrent chordomas were associated with an abnormal karyotype, disease progression, and poor survival. De novo chordomas with normal karyotypes may be amenable to radical resection and adjunctive proton beam therapy. Recurrent and de novo chordomas with abnormal karyotypes were associated with complex cytogenetic abnormalities and a poor prognosis, particularly in the presence of aberrations underlying tumor progression in chromosomes 3, 4, 12, 13, and 14.
脊索瘤的细胞遗传学研究较少，且显示出涉及不同染色体的多种变化。这些异常与脊索瘤的发病机制有关，但这些变化的临床意义尚待确定。在本研究中，作者讨论了一系列经过长期随访的颅底脊索瘤的细胞遗传学变化，并重点关注这些变化对疾病预后、进展和治疗的影响。
研究了64例患者（36例男性和28例女性）脊索瘤的核型，观察其在平均48±37.5个月的随访期内的生存情况以及复发或进展情况。采用标准G显带技术进行核型分析。使用Fisher精确检验和比值比进行统计分析，并生成疾病生存和复发/进展的Kaplan-Meier曲线。
74%的原发脊索瘤核型正常，复发率为3%；核型异常的原发肿瘤复发率为45%（p<0.01）。复发性肿瘤核型异常的发生率较高（75%）。核型异常与正常的病变复发比值比为12。3号、4号、12号、13号和14号染色体的畸变与频繁复发和生存时间缩短有关。95%的进展病例涉及3号和/或13号染色体。当这两条染色体都有畸变时，中位生存时间为4个月（p=0.02）。
核型正常的脊索瘤复发率低，患者生存期长，而复发性脊索瘤与核型异常、疾病进展和生存不良有关。核型正常的原发脊索瘤可能适合根治性切除和辅助质子束治疗。核型异常的复发性和原发脊索瘤与复杂的细胞遗传学异常和不良预后相关，特别是当存在3号、4号、12号、13号和14号染色体上与肿瘤进展相关的畸变时。
