Jaehne Michael, Roeser Kerstin, Jaekel Thorsten, Schepers Jan David, Albert Natalie, Löning Thomas
Ear, Nose and Throat Department, University-Hospital Hamburg-Eppendorf, Hamburg, Germany.
Cancer. 2005 Jun 15;103(12):2526-33. doi: 10.1002/cncr.21116.
Due to the low incidence of salivary duct carcinoma (SDC), only limited data in regard to the biologic behavior of this tumor and its immunohistochemical characteristics are available. The authors analyzed the clinical, molecular, and genetic profile of SDC and identified prognostic factors.
The follow-up of 50 patients with SDC was obtained and paraffin-embedded tumor samples were examined immunohistochemically. In all samples, the expression of Ki-67, HER-2, and the oncoproteins p16 and p53 was examined immunohistochemically, followed by a mutation analysis of p16 and p53. The survival rate was calculated by the Kaplan-Meier method and prognostic variables were analyzed with the log-rank test.
SDC predominantly effected male patients (66%) in their 7th decade of life. SDC mainly occurred in the parotid gland (78%; submandibular gland, 12%; minor salivary glands, 10%). Approximately two-thirds of the patients (33 of 50) presented with a T3/T4 tumor. In 28 patients (56%), cervical lymph node metastasis was present at the time of diagnosis. Local disease recurrence was observed in 48% of patients an average of 17.4 months after initial treatment. Distant disease metastasis developed in 48% of patients an average of 29 months after initial treatment. The average overall survival period was 56.2 months. In the current study, 20.6% of the probes with positive HER-2/neu expression were (+++) positive. p53 was expressed in 83.9% of the tumor samples. In 11.8% of the tumor samples, there was a lack of p16 expression.
Mutations of the p53 gene were more frequent in tumor samples with (++) and (+++) immunoreactivity and mainly affected exons 7 and 8. A mutation of the p16 gene was only found in 1 tumor sample. Expression of HER-2/neu and p53 was statistically linked (P < 0.05) to early local disease recurrence, distant disease metastasis, and survival rates.
由于涎腺导管癌（SDC）发病率较低，关于该肿瘤生物学行为及其免疫组化特征的数据有限。作者分析了SDC的临床、分子和基因特征，并确定了预后因素。
对50例SDC患者进行随访，并对石蜡包埋的肿瘤样本进行免疫组化检查。在所有样本中，免疫组化检测Ki-67、HER-2以及癌蛋白p16和p53的表达，随后对p16和p53进行突变分析。采用Kaplan-Meier法计算生存率，并用对数秩检验分析预后变量。
SDC主要影响70岁左右的男性患者（66%）。SDC主要发生于腮腺（78%；下颌下腺，12%；小涎腺，10%）。约三分之二的患者（50例中的33例）表现为T3/T4期肿瘤。28例患者（56%）在诊断时出现颈部淋巴结转移。48%的患者在初始治疗后平均17.4个月出现局部疾病复发。48%的患者在初始治疗后平均29个月出现远处疾病转移。平均总生存期为56.2个月。在本研究中，HER-2/neu表达阳性的探针中有20.6%为（+++）阳性。83.9%的肿瘤样本中表达p53。11.8%的肿瘤样本中缺乏p16表达。
p53基因的突变在免疫反应性为（++）和（+++）的肿瘤样本中更常见，主要影响外显子7和8。仅在1个肿瘤样本中发现p16基因的突变。HER-2/neu和p53的表达与早期局部疾病复发、远处疾病转移和生存率在统计学上相关（P<0.05）。
