Study On Aldehyde Dehydrogenase-1 Tumor Cells In Ininvasive Micropapillary Carcinoma Of The Breast

ObjectiveMicro-invasive papillary carcinoma (IMPC) of the Breast, a special subtype of invasivebreast cancer with a high incidence of lymph node metastasis and poor prognosis.Breast cancer cells with aaldehyde dehydrogenase-1(ALDH-1)phenotype have been suggested to have tumor-initiating properties with stem cell-like properties.Research on ALDH-lphenotype of tumor stem cell markers in breast invasive micro papillary carcinoma primary tumor and lymph node metastases and clinical significance of the expression,the existence of stem cells inIMPC tumor cells may lead to the presence of high IMPC lymphatic invasion, lymph node metastasis and high resistance.MethodsThe expression, location and distribution of ALDH-1 were examined by immunohistochemical staining in 103 cases with lymph node metastasis of IMPC and 110 cases with lymph node metastasis of invasive ductal carcinoma not otherwise specified (IDC-NOS) without preoperative chemotherapy and radiotherapy, and their relationship between clinicopathological characteristics and prognostic significance were analyzed.Results1. Compared with the control group of IDC-NOS, IMPC werelarger in size (t=-2.888,P=0.004, table 1), higher staged (Z=-2.931, P=0.003), had a higher lymph node metastasis rate (Z=-5.889, P<0.001, tablel) with more nodes involved per case (14.57 in IMPC versus 6.82 in IDC-NOS, t=-5.237, P＜0.001), and exhibitedincreased lymphovascular invasion (Z=14.037, P<0.001)and extranodal extension (Z=11.999,P=0.001);2. IMPC component in accordance with the proportion of the entire tumor, the IMPC divided into four groups:primary tumors,<25% of the 35 cases,25%-49% of the 12 cases,50%-75% of the 12 cases,> 75% of the 44 cases; lymph node metastases,<25% of the 6 cases,25%-49% of the 11 cases,50%-75% of the 12 cases,> 75% of the 74 cases. The Spearman rank correlation analysis showed that the primary tumor and lymph node metastases IMPC component proportion in the entire tumor and lymphatic invasion, lymph node metastasis was no significant correlation between the number(P>0.05);3. ALDH-1 phenotype cells of breast cancer were expressed in the primary tumor and lymph node metastasis of tumor cells, and its expression is consistent (P> 0.05);4. The positive expression rate of ALDH-1 tumor cells was significantly higher in the IMPC group of primary tumor and lymph node metastasis (37.9% in the primary tumor,39/103 cases; lymph node metastasis 47.6%,49/103 cases) than in the IDC-NOS group (21.8% in the primary tumor,24/110 cases; lymph node metastasis 23.6%,26/110 cases) (P＜0.05);5. Expression of ALDH-1 had a significant positive correlation with tumour size histological grade, lymph node metastasis, ER-negative status, PR-negative status, HER2 overexpression in primary tumor and lymph node metastasis of IMPC (P＜0.05),and positive cells of ALDH-1 were highly expressed in the HER2 overexpression and Basal-like breast cancers. Expression of ALDH-1 had a significant positive correlation with histological grade, lymph node metastasis of IMPC(P<0.05);6. The disease-free survival of IMPC group patients was significantly shorter than IDC-NOS group patients, with statistical difference (P=0.003).The disease-free survival of ALDH-1 positive patients was significantly lower than that of ALDH-1 negative patients in the IMPC with lymph node-positive of primary tumor and lymph node metastasis, with statistical difference (P<0.05), The disease-free survival of ALDH-1 positive patients was significantly lower than that of ALDH-1 negative patients in the IDC-NOS. In multivariate analysis ALDH-1 positive expression in metastatic lesions was associated with a worse prognosis (P=0.005).Conclusion1. IMPC had a higher lymphatic invasion and lymph node metastasis ratewith more nodes involved per case and poor prognosis;2. The percentage of IMPC components in the whole tumor was not significantly associated with lymph node metastasis rate or the number of positive lymph nodes;3. Stem cells exist in primary tumor and lymph node metastases of the breastIMPC, and there may be a higher proportion of stem cells;4. In IMPC, tumor size,histological grade andpathological staging are closely related to the extent of lymph nodes involved;5. ALDH-1 could be considered as biomarkes of prognosis and as a new target for IMPC therapy;6. ALDH-1 could be used as an independent factor for predicting the prognosis of patients with lymph node-positive breast IMPC and the existence of stem cells in IMPC tumor cells may lead to the presence of high IMPC lymphatic invasion, lymph node metastasis and high resistance.