Martínez-López E, Abad A, Font A, Monzó M, Ojanguren I, Pifarré A, Sánchez J J, Martín C, Rosell R
Laboratory of Molecular Biology of Cancer, University Hospital Germans Trias i Pujol, Barcelona, Spain.
Gastroenterology. 1998 Jun;114(6):1180-7. doi: 10.1016/s0016-5085(98)70423-8.
BACKGROUND & AIMS: Loss of heterozygosity (LOH) on chromosome 18q is frequent in colorectal cancer (CRC) and has been associated with poor prognosis in stage II tumors. This study investigated the frequency of LOH in sporadic CRC and its effect on patient prognosis.
One hundred forty-four patients were screened for LOH at 18q by polymerase chain reaction using three polymorphic microsatellite markers.
Nineteen patients were excluded because their tumors showed microsatellite instability in at least one marker. Of the remaining 125 patients, 121 were informative in at least one marker; 45% (54 of 121) showed 18q LOH. Five-year survival was 42% in those with 18q LOH and 73% in those without 18q LOH (P = 0.008). Multivariate analysis showed that tumor side (P = 0.0001) and 18q LOH (P = 0.01) were the only independent prognostic factors. Examining markers individually showed that only the lost of D18S474 had a significant influence on survival in patients with stage II CRC (P = 0.016).
18q LOH indicates an unfavorable outcome in patients with stage II CRC. Our results emphasize the importance of the 18q21.1 region, where several tumor-suppressor genes have been mapped. Microsatellite analysis may be useful in identifying high-risk patients who might benefit from adjuvant therapy.
18号染色体长臂杂合性缺失（LOH）在结直肠癌（CRC）中很常见，并且与II期肿瘤的预后不良相关。本研究调查了散发性结直肠癌中LOH的频率及其对患者预后的影响。
使用三个多态性微卫星标记，通过聚合酶链反应对144例患者进行18号染色体长臂LOH筛查。
19例患者被排除，因为他们的肿瘤在至少一个标记中显示微卫星不稳定性。在其余125例患者中，121例在至少一个标记中具有信息性；45%（121例中的54例）显示18号染色体长臂LOH。18号染色体长臂LOH患者的五年生存率为42%，无18号染色体长臂LOH患者的五年生存率为73%（P = 0.008）。多变量分析显示，肿瘤部位（P = 0.0001）和18号染色体长臂LOH（P = 0.01）是仅有的独立预后因素。单独检查标记显示，只有D18S474的缺失对II期结直肠癌患者的生存有显著影响（P = 0.016）。
18号染色体长臂LOH表明II期结直肠癌患者预后不良。我们的结果强调了18q21.1区域的重要性，该区域已定位了几个肿瘤抑制基因。微卫星分析可能有助于识别可能从辅助治疗中获益的高危患者。
