Prognostic Factors Expression In Rat Breast Cancer Incisioned In Different Time And In Human Breast Cancer

IntroductionBreast cancer is a kind of common neoplasm in female,the incidence increases yearly.Early diagnosis and comprehensive therapy is very important.However the therapy choice is still difficult until now,some patients are overtherapied,some are not enough.So we should try to find more prognostic factors other than the traditional factors,such as histological grade,clinical stage,lymph node metastasis.We used 7,12 dimethylbenz anthracene(DMBA)to induce breast cacer in Wistar rats,the same tumor in same rat was incisioned in different time,studied the pathological factors and the expression of tumor markers,tried to find which one could be prognostic fator.For human breast cancer,we retrospectively studied the relations between the expression and survival.MethodWe used 40 healthy female Wistar rats,8 weeks old,gave them DMBA 20mg per 100g body weight,animal model was established.After DMBA was given 20 weeks and 24 weeks,the same tumor in same rat was incisioned.All the rats were killed after 24 weeks.We collected 54 cases of breast cancer from June 2002 to June 2007,all the patients received standard therapy,and finished all therapy cycles.The mortality rate of rats,tumor incidence rate,tumor size were observed.First HE staining,and then immunohistochemical method was used to detect the expression of estrogen receptor ER,progesterone receptor PR,C-erbB-2(human epithelial growth factor receptor 2), and mammaglobin.Pathological factors included histological grade,comedo necrosis and extensive intraductal carinoma EIC.ResultsIn the 40 rats,32 rats lived until 24 weeks after DMBA given,20 rats(62.5%)of the 32 rats got breast tumors,the total bearing cancer number was 28.All were breast cancer,27 caseswas invasive breast cancer,and only 1 was intraductal carcinoma. Histological grade,Ⅰgrade:17 cases(60.71%),Ⅱgrade:8 cases(28.57%),Ⅲgrade (10.71%).In all the tumors,10 tumors were incisioned in 20 weeks after DMBA given, in the residual tumors,2 disappeared,and 8 grow.Compared the 8 cases,the pathological factors of HE staining did not changed,remained the same histological grade.Immunohistochemical staining results of rats:mean MIB-1 index of 24 weeks was 2.25%±2.30%,ER staining was positive in 60.7%cases.Immunohistochemical staining results of human:C-erbB-2 was positive in 57.4%(31/54)cases.In the high histological grade cases and in comedo necrosis positive cases,the c-erbB-2 expression was higher,c-erbB-2 expression was not related to age,menopause status,ER,lymph node metastasis,EIC and the expression of mammaglobin.Mean MIB-1 index was 18.3%±14.1%,it associated with histological grade(P<0.05)and diseased free survival(P<0.05),had no relations with comedo necrosis,age,menopause status,ER, lymph node metastasis,EIC and the expression of mammaglobin.Conclusions1 Carcinogenesis process:epithelial hyperplasia→ductal atypical hyperplasia→carcinogenesis→invasive ductal carcinoma,the incidence of carcinoma in situ is very low2 The pathological morphology and etiology of DMBA induced rat breast cancer is similar to human breast cancer,so this animal model can be used in breast cancer study3 With the time progress,the cell proliferation increases4 MIB-1 index is associated with disease free survival,can be used as a reliable prognostic factor,when MIB-1 index is more than 13.2%,the patient is in high risk 5 Mammaglobin can not be used as prognostic factor...