Carey T E, Wolf G T, Hsu S, Poore J, Peterson K, McClatchey K D
Otolaryngol Head Neck Surg. 1987 Mar;96(3):221-30. doi: 10.1177/019459988709600301.
The murine monoclonal antibody (A9), raised to the human squamous cell carcinoma (SCC) cell-line UM-SCC-1, defines a squamous cell antigen associated with aggressive biologic behavior of SCC cell lines in vivo and in vitro. In the present investigation, A9 antigen was detected in tissue sections from 37 consecutive, previously untreated patients with SCC of the head and neck. All tumors were positive for A9 binding, although three distinct patterns (reflecting different intensities of A9 expression) were identified. The intensity of A9 expression was independent of primary tumor site, tumor differentiation, keratinization, or growth pattern. The frequency of high expression (Pattern 1) grew with increasing T class, N class, and tumor stage, and was associated with loss of blood group expression in the tumor and with low levels of lymphocyte infiltration in the tumor. Strong A9 expression had a statistically significant association with low nuclear grade (i.e., tumors with more mature and fewer enlarged nuclei, P = 0.019), low vascular/stromal response (i.e., patchy response rather than continuous, P = 0.014), and impaired in vitro lymphokine production by peripheral blood leukocytes (P = 0.0011). Of greatest interest, however, was the strong association of high A9 expression with shortened disease-free interval (DFI) (P = 0.085) and survival (P = 0.081) relative to patients with weak A9 tumor staining (Patterns 2 and 3). Similarly, the loss of blood group antigen expression was strongly associated with decreased DFI (P = 0.038) and survival (P = 0.062). While neither Pattern 1 A9 expression nor loss of blood group reach statistical significance in prediction of survival, the combination of Pattern 1 A9 expression and loss of blood group expression in primary tumors was significantly associated, both with decreased disease-free interval (P = 0.017) and with decreased overall survival (P = 0.011) (median length of follow-up = 22 months). The length of follow-up (LFU) ranged from 2 to 38 months, with a median LFU of 22 months. While the number of patients (37) is small, the significant association between the expression of these cell-surface markers with relapse and survival indicates that immunohistologic staining of the primary tumor will be an important prognostic indicator useful in identification of individual patients at greatest risk of recurrence or early death from head and neck cancer, independent of tumor size, site, or stage at presentation. These markers may thus provide means of selecting patients who should receive adjuvant therapy and more intensive monitoring for the early detection of recurrent disease.
针对人鳞状细胞癌（SCC）细胞系UM-SCC-1产生的鼠单克隆抗体（A9），可识别一种与SCC细胞系在体内和体外侵袭性生物学行为相关的鳞状细胞抗原。在本研究中，对37例连续的、未经治疗的头颈部SCC患者的组织切片进行了A9抗原检测。所有肿瘤的A9结合均呈阳性，不过可识别出三种不同模式（反映A9表达强度不同）。A9表达强度与原发肿瘤部位、肿瘤分化、角化或生长模式无关。高表达（模式1）的频率随T分级、N分级和肿瘤分期增加而升高，且与肿瘤中血型表达缺失及肿瘤中淋巴细胞浸润水平低相关。A9强表达与低核分级（即核更成熟、肿大核更少的肿瘤，P = 0.019）、低血管/间质反应（即散在反应而非连续反应，P = 0.014）以及外周血白细胞体外淋巴因子产生受损（P = 0.0011）具有统计学显著相关性。然而，最令人感兴趣的是，相对于A9肿瘤染色弱的患者（模式2和3），A9高表达与无病间期（DFI）缩短（P = 0.085）和生存率降低（P = 0.081）密切相关。同样，血型抗原表达缺失与DFI降低（P = 0.038）和生存率降低（P = 0.062）密切相关。虽然模式1的A9表达和血型缺失在预测生存率方面均未达到统计学显著性，但原发肿瘤中模式1的A9表达与血型表达缺失相结合，与无病间期缩短（P = 0.017）和总生存率降低（P = 0.011）均显著相关（中位随访时间 = 22个月）。随访时间（LFU）为2至38个月，中位LFU为22个月。虽然患者数量（37例）较少，但这些细胞表面标志物的表达与复发和生存率之间的显著相关性表明，原发肿瘤的免疫组织化学染色将是一个重要的预后指标，有助于识别头颈部癌复发或早期死亡风险最高的个体患者，而与肿瘤大小、部位或就诊时的分期无关。因此，这些标志物可能为选择应接受辅助治疗以及进行更密切监测以早期发现复发性疾病的患者提供方法。
