Clinical Significance Of Lymph Nodes Micro-metastasis Of Breast Carcinoma In Situ With/without Micro-invasion

IntroductionBreast cancer is one of malignant tumors of female with increasing incidence and mortality rate for years in the world. It was showed on the second place among the malignant tumors of female in China. Invasion and metastasis are the most important biological features of breast carcinoma and the key factors for survival. With the development of medical tech, more and more breast cancers in situ were found in the past decade, but with an increasing rates for new diagnosis patients. Axillary lymph nodes is one of the important factors to predict recurrence and survival, and also for choosing regime of adjunctive therapy. In this study, micro-metasis in lymph nodes was investigated in breast carcinoma in situ patients, using immumohistochemistry method (Antibody: Cytokeratin19, CK19), which showed more sensitive to epithelial cell in breast cancer, so as to clarify its clinical significance of lymph node micro-metastasis after 72 months follow-up (median: 35 months) in human breast caner.Materials and methodsFifty-eight patients with final diagnosis DCIS and DCISMI were collected from the Surgical Department of Oncology, No.1 Affiliated Hospital of China Medical University, from 2000～2005. Among the 58 patients (age 30～72 years old, average 45.8), 24 patients were DCIS, and 34 patients were DCISMI. 798 lymph nodes were investigated from all group of 58 patients(average 13.76). And positive results of axillary nodes micro-metastasis were showed in 7 patients, including 1 DCIS and 6 DCISMI with total of 8 micro-metastasis lymph nodes). Follow-up was finished in all group of 58 patients, between 15～73 months (median,35 months). Two DCISMI patients recurred within 2 years after surgery operation.For up-regulating the sensitivity to cluster or micro-metastasis in the lymph nodes, streptavidin peroxidase method was used (Multi antibody: CK19, S-P kit, Wuhan Boster Biocompany). Briefly for the research method as follow: The section were deparaffinized, water processed, then treated by 0.1% trytsin to expose antigen and 3% hydrogen peroxide for 30 minutes to quench the endogenous peroxidase activity. After that, all were incubated for 30 minutes with normal non-immuneserum to eliminate nonspecific staining, and then incubated with primary antibody at 4℃overnight. This was followed by incubation with biotin-labelled condary antibody and streptavition-peroxidase complex for 30 minutes. The color was developed with diaminobenzidine and the section were couterstain with harmatoxylin. The blank control were carried out by replaceing the primary antibody with PBS. IHC CK19 positive staining is located in plasma of tumor cells. Under ocular micro-metastasis, measure the size using the AJCC classification system(6^th edition).The statistical method were according to x² test to study the relationship between carcinoma in situ biological characters(age, tumor size, location, menses, family history, pathological type,ER,PR,C-erbB2), micro-metastasis and outcome after systemic treatment in human breast cancer.Result1. Axillary lymph nodes micro-metastasis in DCIS and DCISMIOur data show that lymph nodes micro-metastasis were detected in 7 of 58 cases(12.1%), including one case of DCIS and six case of DCISMI with total of 8 micro-metastasis lymph nodes.2.The difference of biological characters between DCIS and DCISMIAfter axillary lymph nodes dissected and routine pathological diagnosis, axillary lymph nodes metastasis was found in 7 patients, one patient with DCIS(4.2%) and six patients with DCISMI(17.6%). The rate of axillary lymph nodes micro-metastasis was 17.6% in DCISMI patients compared with 4.2% in DCIS. No significant of other biological characters was found between the group of DCIS and DCISMI in the rate of axillary lymph nodes metastasis, referring to other biological characters such as age, tumor size, location, family history,HER-2,ER,PR.3.Different biological behavior between lymph nodes micro-metastasis positive and negative group.The rate of micro-metastasis was statistical significance between the group of age <40 years and≥40 years patients. The expression of PR protein was statistical significance between two group. And all 7 metastasis positive patients' expression of PR were negative. It suggest that rate of lymph nodes metastasis was higher in patients whose expression of PR negative.4.Recurrence was found in 2 of 34 DCISMI breast cancer patients within 2 years after the operative treatment, meanwhile, no recurrence was found in DCIS.Conclusion1.There were axillary lymph nodes micro-metastasis in DCIS and DCISMI patients.2.Because of micro-invasion component, axillary lymph nodes metastasis rate in DCISMI was higher than that in DCIS, significantly. Some experts indicated that recessive micro-invasion resulted in metastasis or micro-metastasis in lymph nodes of DCIS patients, serial sections for tumor tissues may work as one of the useful way to discover the real micro-metastasis in the lymph nodes of human breast cancers.3. Age and PR expression may be the influnced factor of micro-metastasis.