Stenman J, Hedström J, Grénman R, Leivo I, Finne P, Palotie A, Orpana A
Department of Clinical Chemistry, University of Helsinki and Laboratory Department of Helsinki University Central Hospital, Helsinki, Finland.
Int J Cancer. 2001 Jan 20;95(1):39-43. doi: 10.1002/1097-0215(20010120)95:1<39::aid-ijc1007>3.0.co;2-n.
Squamous cell carcinoma antigen (SCCA) is widely used as a serum marker in cancers of the uterine cervix, the head and neck, lung and esophagus. Two isoforms of SCCA, deriving from 2 highly homologous serine proteinase inhibitor genes, are co-expressed in normal and malignant squamous epithelium, but it is mainly the acidic isoform SCCA2 that is present in the circulation of cancer patients. We studied the relative levels of SCCA2 and SCCA1 mRNA in frozen sections of squamous cell carcinomas of the head and neck (SCCHN) in relation to disease recurrence, using a new reverse transcription-polymerase chain reaction-based technique for accurate quantitation of relative mRNA levels. Primary tumors from 30 SCCHN patients, recurrent tumors from 11 patients and normal epithelium from 16 controls were examined. In patients responding to initial therapy (n = 26), an elevated SCCA2/SCCA1 mRNA ratio in the primary tumor predicted recurrence independent of clinical stage (p = 0.011). The relative risk of developing a recurrence was 7.2 (CI 1.2-13.3) in patients with elevated vs. normal SCCA2/SCCA1 mRNA ratios. We demonstrate that subtle differences in expression levels of the SCCA genes are reflected in the course of the SCCHN disease and may provide a target for molecular grading of SCCHN tumors. If this finding can be confirmed in a larger study the SCCA2/SCCA1 mRNA ratio in primary tumors could be useful for individual selection of treatment strategy for patients with head and neck cancer.
鳞状细胞癌抗原（SCCA）被广泛用作子宫颈癌、头颈癌、肺癌和食管癌的血清标志物。SCCA的两种同工型来源于2个高度同源的丝氨酸蛋白酶抑制剂基因，在正常和恶性鳞状上皮中共同表达，但在癌症患者的循环系统中主要存在的是酸性同工型SCCA2。我们使用一种基于逆转录-聚合酶链反应的新技术来准确定量相对mRNA水平，研究了头颈鳞状细胞癌（SCCHN）冰冻切片中SCCA2和SCCA1 mRNA的相对水平与疾病复发的关系。检测了30例SCCHN患者的原发肿瘤、11例患者的复发肿瘤以及16例对照的正常上皮。在对初始治疗有反应的患者（n = 26）中，原发肿瘤中SCCA2/SCCA1 mRNA比值升高可独立于临床分期预测复发（p = 0.011）。SCCA2/SCCA1 mRNA比值升高的患者与正常患者相比，复发的相对风险为7.2（CI 1.2 - 13.3）。我们证明SCCA基因表达水平的细微差异反映在SCCHN疾病的进程中，可能为SCCHN肿瘤的分子分级提供一个靶点。如果这一发现能在更大规模的研究中得到证实，原发肿瘤中的SCCA2/SCCA1 mRNA比值可能有助于为头颈癌患者个体选择治疗策略。
