Braakhuis Boudewijn J M, Brakenhoff Ruud H, Leemans C René
Department of Otolaryngology/Head and Neck Surgery, Room 1D 116, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
Oncologist. 2005 Aug;10(7):493-500. doi: 10.1634/theoncologist.10-7-493.
Recent molecular genetic studies provide evidence that the majority of, if not all, head and neck squamous cell carcinomas (HNSCCs) develop within a contiguous field of preneoplastic cells. Cells of a field show genetic alterations associated with the process of carcinogenesis. A subclone in a field gives rise to an invasive carcinoma. An important implication of this knowledge is that, after surgery of the initial carcinoma, part of the field may remain in the patient. A field with preneoplastic cells that share genetic alterations with cells of the excised tumor has been detected in the resection margins of at least 25% of patients, indicating that this frequently occurs. Fields can be much larger than the actual carcinoma, sometimes having a diameter >7 cm. When a field remains after resection of the tumor, the risk for another carcinoma, designated as a second field tumor (SFT), is considerably greater. It is important to realize that an SFT develops from preneoplastic cells clonally related to the initial tumor. In this respect, it should be discriminated from a recurrent carcinoma that has developed from minimal residual cancer that was left behind and from a second primary tumor that independently develops from the initial carcinoma. Patients at risk for SFTs belong to a unique patient group for whom intense surveillance is indicated and chemoprevention is an attractive option. The priorities are to identify the patients in whom a remaining field will progress to cancer and to find the genes involved. With this knowledge, highly efficient clinical prevention trials, including those using the local application of therapeutic agents, can be designed. It is important to note that SFTs also may occur after treatment of various other cancers, including those of the bladder, skin, esophagus, lung, cervix, breast, and colon.
最近的分子遗传学研究表明，大部分（如果不是全部）头颈部鳞状细胞癌（HNSCC）是在一个连续的癌前细胞区域内发生的。该区域的细胞显示出与致癌过程相关的基因改变。该区域中的一个亚克隆会发展成浸润性癌。这一认识的一个重要意义是，在对原发性癌进行手术后，该区域的一部分可能仍留在患者体内。在至少25%的患者的手术切缘中检测到了含有与切除肿瘤细胞共享基因改变的癌前细胞的区域，这表明这种情况经常发生。这些区域可能比实际的癌大得多，有时直径>7厘米。当肿瘤切除后该区域仍存在时，发生另一种癌（称为第二区域肿瘤，SFT）的风险会大大增加。必须认识到，SFT是由与初始肿瘤克隆相关的癌前细胞发展而来的。在这方面，它应与由残留的微小残余癌发展而来的复发性癌以及独立于初始癌发展而来的第二原发性癌区分开来。有SFT风险的患者属于一个独特的患者群体，对他们需要进行密切监测，化学预防是一个有吸引力的选择。首要任务是识别出剩余区域会发展为癌症的患者，并找出相关基因。有了这些知识，就可以设计出高效的临床预防试验，包括那些使用局部应用治疗药物的试验。需要注意的是，SFT也可能在治疗各种其他癌症后发生，包括膀胱癌、皮肤癌、食管癌、肺癌、宫颈癌、乳腺癌和结肠癌。
