van Oijen M G, Leppers Vd Straat F G, Tilanus M G, Slootweg P J
Department of Pathology, University Medical Center, Utrecht, The Netherlands.
Cancer. 2000 Feb 15;88(4):884-93. doi: 10.1002/(sici)1097-0142(20000215)88:4<884::aid-cncr20>3.0.co;2-s.
Chemoprevention and cessation of smoking and alcohol may prevent development of multiple tumors (MTs) in the aerodigestive tract if new MTs arise independently, but they are of no benefit if MTs are due to migration of an already transformed clone of tumor cells. This issue was addressed in this study by investigation of the clonality among MTs.
Mutation analysis of the entire coding region of p53 and loss of heterozygosity (LOH) pattern analysis of microsatellite markers on chromosome arms 3p, 9p, and 17p are promising for the investigation of clonality. In the first part of this study, the authors established the variability and stability of these clonal markers by comparing primary head and neck squamous cell carcinomas (HNSCCs) with their metastases. In the second part of this study, the authors evaluated nine patients with multiple HNSCCs using these markers. In the final part, the authors illustrate the use of these clonal markers in 11 patients for whom there was diagnostic uncertainty as to whether their second squamous cell carcinoma was either a new primary tumor, a metastasis, or a recurrence.
Both p53 gene mutations and LOH patterns were stable during tumor progression. Furthermore, the variability of p53 gene mutations was high. More than 90% of the tumors contained a p53 mutation. A particular mutation never occurred more than twice in a total of 69 primary HNSCCs. Five of 69 cases presented a common mutation. In contrast, LOH patterns showed less variability; they were identical in 5 of 16 cases. The metachronous HNSCCs from nine patients all showed different p53 mutations, and in the three cases that were subjected to LOH analysis different patterns were observed. All 11 patients for whom there was diagnostic uncertainty about the origin of their second squamous cell carcinoma could be categorized as having multiple primary tumors, disseminated disease, or recurrent disease.
Metachronous HNSCCs at different locations are not clonally related and thus have not developed from the migration of tumor cells.
如果新发的多原发肿瘤（MTs）是独立发生的，那么化学预防以及戒烟和戒酒可能会预防上消化道和呼吸道的多种肿瘤的发生；但如果MTs是由已转化的肿瘤细胞克隆迁移所致，那么这些措施则毫无益处。本研究通过调查MTs之间的克隆性来探讨这一问题。
p53基因整个编码区的突变分析以及3号染色体短臂、9号染色体短臂和17号染色体短臂上微卫星标记的杂合性缺失（LOH）模式分析，对于克隆性研究很有前景。在本研究的第一部分，作者通过比较原发性头颈部鳞状细胞癌（HNSCCs）及其转移灶，确定了这些克隆标记的变异性和稳定性。在本研究的第二部分，作者使用这些标记评估了9例患有多发性HNSCCs的患者。在最后一部分，作者举例说明了这些克隆标记在11例患者中的应用，这些患者的第二个鳞状细胞癌究竟是新发原发性肿瘤、转移瘤还是复发病灶存在诊断上的不确定性。
在肿瘤进展过程中，p53基因突变和LOH模式均保持稳定。此外，p53基因突变的变异性很高。超过90%的肿瘤含有p53突变。在总共69例原发性HNSCCs中，特定突变从未出现过两次以上。69例中有5例出现共同突变。相比之下，LOH模式的变异性较小；16例中有5例相同。9例患者的异时性HNSCCs均显示出不同的p53突变，在接受LOH分析的3例中观察到不同的模式。所有11例第二个鳞状细胞癌起源存在诊断不确定性的患者都可归类为患有多原发性肿瘤、播散性疾病或复发性疾病。
不同部位的异时性HNSCCs并非克隆相关，因此并非由肿瘤细胞迁移发展而来。
