Leong P P, Rezai B, Koch W M, Reed A, Eisele D, Lee D J, Sidransky D, Jen J, Westra W H
Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
J Natl Cancer Inst. 1998 Jul 1;90(13):972-7. doi: 10.1093/jnci/90.13.972.
In patients with head and neck squamous cell carcinoma (HNSCC), a squamous cell carcinoma (SCC) in the lung represents either another primary tumor or a metastasis. This distinction greatly influences patient prognosis and could guide treatment strategies, but the nature of a solitary lung nodule is often difficult to discern by use of standard clinical and histologic parameters. Comparison of genetic alterations in the tumors could resolve this dilemma.
We compared paired tumors from 16 patients with HNSCC and a solitary lung SCC for loss (i.e., deletion) of loci on chromosomal arms 3p and 9p. Losses at these loci occur early during neoplastic transformation of the respiratory tract. DNA from microdissected tumors and normal tissues was subjected to polymerase chain reaction-based microsatellite analysis. An effort was also made to distinguish primary lung cancers from lung metastases on the basis of clinical and histopathologic features.
In most cases, comparison of genetic alterations clarified the relationship between the lung tumor and the primary HNSCC. The paired tumors from 10 patients had concordant patterns of loss at all loci suggesting metastatic spread, whereas three paired tumors had discordant patterns of loss at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings.
CONCLUSIONS/IMPLICATIONS: In patients with HNSCC and a solitary SCC in the lung, microsatellite analysis provides a rapid genetic approach for discerning clonal relationships. In such patients, we found that a solitary SCC in the lung more likely represents a metastasis than an independent lung cancer. Microsatellite analysis could potentially be applied to any patient with multiple tumors, where tumor relationships are not clear on clinical, radiographic, or even histopathologic grounds.
在头颈部鳞状细胞癌（HNSCC）患者中，肺部的鳞状细胞癌（SCC）可能代表另一原发性肿瘤或转移瘤。这种区分对患者预后有很大影响，并可指导治疗策略，但仅凭标准的临床和组织学参数往往难以辨别孤立性肺结节的性质。比较肿瘤中的基因改变可以解决这一难题。
我们比较了16例HNSCC患者的配对肿瘤与孤立性肺SCC，以检测3号染色体短臂和9号染色体短臂上基因座的缺失（即缺失）情况。这些基因座的缺失发生在呼吸道肿瘤转化的早期。对显微切割的肿瘤和正常组织的DNA进行基于聚合酶链反应的微卫星分析。还试图根据临床和组织病理学特征区分原发性肺癌和肺转移瘤。
在大多数情况下，基因改变的比较明确了肺肿瘤与原发性HNSCC之间的关系。10例患者的配对肿瘤在所有基因座上的缺失模式一致，提示转移扩散，而3例配对肿瘤在所有基因座上的缺失模式不一致，提示肿瘤独立起源。这些观察结果得到了临床和病理结果的支持。
结论/启示：在患有HNSCC和肺部孤立性SCC的患者中，微卫星分析提供了一种快速的基因方法来辨别克隆关系。在这类患者中，我们发现肺部孤立性SCC更可能是转移瘤而非独立的肺癌。微卫星分析可能适用于任何患有多种肿瘤的患者，这些患者的肿瘤关系在临床、影像学甚至组织病理学基础上都不明确。
