Abstract：
The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model.
摘要：
该研究的目的是使用实验性两阶段化学诱导的致癌方案在FVB/N小鼠的背侧皮肤上研究EGFR和HER-2癌基因的表达。40只雌性FVB/N小鼠4周龄，随机分组后分为一个对照组（n=8）和两个实验组（A组：n=16，B组：n=16）。两阶段致癌方案，有牵连，包括对剃须的背侧皮肤进行97.4nmolDMBA的初始治疗，然后在A组13周后和B组20周后进行32.4nmolTPA应用的后续治疗。对照组C，没有接受治疗。每周检查皮肤的肿瘤发展。实验后,将动物安乐死用于组织分析。实验组皮肤病变的组织学状态与肿瘤进展（从发育不良到低分化癌）非常吻合。对肿瘤切片进行组织学和免疫组织化学评估。EGFR在癌前和恶性肿瘤中的表达显著增高(分别为p=042和p=008),虽然在良性肿瘤中倾向于更高（p=079），与正常组织学相比。此外，恶性肿瘤中EGFR阳性表达的平均百分比显著高于良性肿瘤(p<001).HER-2在癌前肿瘤和恶性肿瘤中表达显著增高(分别为p=042和p=015),虽然在良性肿瘤中倾向于更高（p=085），与正常组织学相比。此外，恶性肿瘤中HER-2阳性表达的平均百分比显著高于良性肿瘤(p=005).该研究表明，在FVB/N小鼠中，经过两阶段化学诱导的致癌作用，与正常组织相比,癌前和恶性皮肤病变中EGFR和HER-2癌基因的表达显著增加.这表明这些癌基因在该模型中皮肤肿瘤进展中的潜在早期作用。
