Tabor M P, Brakenhoff R H, van Houten V M, Kummer J A, Snel M H, Snijders P J, Snow G B, Leemans C R, Braakhuis B J
Department of Otolaryngology/Head and Neck Surgery, Vrije Universiteit Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Clin Cancer Res. 2001 Jun;7(6):1523-32.
In 1953, Slaughter et al. [D. P. Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] proposed the concept of field cancerization in patients with squamous cell carcinoma of the head and neck (HNSCC) and discussed its clinical significance for the development of second primary tumors and local recurrences. To define the process of field cancerization and its putative clinical implications, we analyzed genetic aberrations in HNSCC and the accompanying macroscopically normal mucosa. In 28 HNSCC patients, loss of heterozygosity was determined in tumor and five noncontiguous mucosal biopsies using eight microsatellite markers at 9p, 3p, and 17p. For patients who showed loss of heterozygosity in their mucosal biopsies, all margins of the surgical specimen were subsequently analyzed to determine the extension of the field. In these cases, additional markers at 8p, 13q, and 18q as well as p53 mutations were included to determine subclonal differences between field and tumor. Genetically altered fields were detected in 36% (10 of 28) of the HNSCC patients. The field varied in size between patients and consisted of genetically different subclones. In 7 of 10 cases, the field extended into the surgical margins. One particular patient with a genetically altered field in a surgical margin developed a local recurrence after 28 months of follow-up. Microsatellite analysis showed that this recurrence had more molecular markers in common with the nonresected premalignant field than with the original tumor, suggesting that this persistent field has progressed further into a new malignancy. Our data show that genetically altered mucosa remains after treatment in a significant proportion of HNSCC patients, which may explain in part the high frequency of local recurrences and second primary tumors. Adequate identification and risk assessment of these genetically altered fields may have profound implications for future patient management.
1953年，斯劳特等人[D. P. 斯劳特等人，《癌症（费城）》，6: 963 - 968，1953]提出了头颈部鳞状细胞癌（HNSCC）患者的场癌化概念，并讨论了其对第二原发肿瘤发生和局部复发的临床意义。为了界定场癌化过程及其可能的临床影响，我们分析了HNSCC及其伴发的大体正常黏膜中的基因畸变情况。在28例HNSCC患者中，使用位于9p、3p和17p的8个微卫星标记，测定肿瘤组织及5份不相邻黏膜活检组织中的杂合性缺失情况。对于黏膜活检组织显示杂合性缺失的患者，随后对手术标本的所有切缘进行分析以确定场的范围。在这些病例中，纳入位于8p、13q和18q的额外标记以及p53突变情况，以确定场与肿瘤之间的亚克隆差异。在36%（28例中的10例）的HNSCC患者中检测到基因改变的场。不同患者的场大小各异，且由基因不同的亚克隆组成。10例中有7例，场延伸至手术切缘。1例手术切缘存在基因改变场的特殊患者在随访28个月后出现局部复发。微卫星分析显示，该复发灶与未切除的癌前病变场具有更多共同分子标记，而非与原发肿瘤，这表明这个持续存在的场已进一步发展为新的恶性肿瘤。我们的数据表明，相当一部分HNSCC患者治疗后仍存在基因改变的黏膜，这可能部分解释了局部复发和第二原发肿瘤的高发生率。对这些基因改变场进行充分识别和风险评估可能对未来患者管理具有深远影响。
