Nagler Rafael M, Kerner Hedviga, Ben-Eliezer Shoshana, Minkov Ira, Ben-Itzhak Ofer
Department of Pathology, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Oncology. 2003;64(4):389-98. doi: 10.1159/000070298.
The clinical characteristics and survival probability rate of 36 patients with salivary gland malignancies and 10 patients with benign salivary tumors were summarized in relation to the immunohistological analysis of the tumor, apoptotic-related markers and apoptosis rate. The expression of the markers examined - Bcl-2, c-erbB-2, p53 - was detected in paraffin sections of the tumors by the streptavidin-biotin peroxidase method following heat-induced antigen retrieval, and the apoptosis rate was determined by the TUNEL method.
The overall 5-year survival probability was 61% for patients with malignant tumors and 100% for those with benign tumors. The survival probability of patients over 60 at diagnosis was significantly lower than that of younger patients. Patients whose malignant tumors were larger than 2 cm at diagnosis had worse survival than those with smaller tumors. The survival probability of patients whose malignant tumors were located in the submandibular glands was significantly lower than that of patients whose malignancies were located in the parotid and minor salivary glands. The survival probability of patients who demonstrated positive staining for c-erbB- 2 or TUNEL was lower than for those with negative staining. Gender, the existence of concomitant non-salivary malignancies and ethnic origin had no significant impact on survival.
Our results demonstrated significant positive staining in the salivary tumorigenic tissue but not in the surrounding non-tumorigenic tissue examined for TUNEL, c-erbB-2, Bcl-2 and p53, pointing to a biological role for all four markers in the tumorigenic process which is yet to be elucidated. Significant reduction in survival was related to the specific location of the tumor in the submandibular gland, its size and older age of patient. Survival was also found to be significantly reduced when positive staining was demonstrated in the tumor tissue for TUNEL or c-erbB-2, more so for concomitant positive staining of both markers. Clinically, the most important result of the current study is that the survival rate of the patients examined with salivary tumors larger than 2 cm, with positive staining for both TUNEL and c-erbB-2, was 0 (p = 0.0001)!
通过对肿瘤的免疫组织学分析、凋亡相关标志物及凋亡率，总结36例涎腺恶性肿瘤患者和10例涎腺良性肿瘤患者的临床特征及生存概率。采用链霉亲和素-生物素过氧化物酶法，在热诱导抗原修复后检测肿瘤石蜡切片中所检测标志物——Bcl-2、c-erbB-2、p53的表达，并通过TUNEL法测定凋亡率。
恶性肿瘤患者的总体5年生存概率为61%，良性肿瘤患者为100%。诊断时年龄超过60岁的患者生存概率显著低于年轻患者。诊断时恶性肿瘤大于2 cm的患者生存情况比肿瘤较小的患者差。恶性肿瘤位于下颌下腺的患者生存概率显著低于位于腮腺和小涎腺的患者。c-erbB-2或TUNEL染色呈阳性的患者生存概率低于染色阴性的患者。性别、是否存在伴发非涎腺恶性肿瘤及种族对生存无显著影响。
我们的结果显示，在检测的涎腺致瘤组织中，TUNEL、c-erbB-2、Bcl-2和p53均呈显著阳性染色，而在周围非致瘤组织中未出现，这表明所有这四种标志物在致瘤过程中具有生物学作用，但其作用机制尚待阐明。生存概率显著降低与肿瘤在下颌下腺的特定位置、肿瘤大小及患者年龄较大有关。当肿瘤组织中TUNEL或c-erbB-2染色呈阳性时，尤其是两者同时呈阳性染色时，生存概率也显著降低。临床上，本研究最重要的结果是，对于肿瘤大于2 cm且TUNEL和c-erbB-2染色均呈阳性的涎腺肿瘤患者，其生存率为0（p = 0.）！
