Expression Of Selectins And Their Ligand In Invasive Micropapillary Carcinoma Of The Breast

Objective:Invasive micropapillary carcinoma(IMPC)of the breast is known to have a high potential to metastasize to the axillary lymph node,but the mechanisms underlying the lymphotroposm of this distinct variant remained unknown.Selectins and its ligand Sialyl Lewis X(sLe~x)are believed to play an important role in tumor metastasis.The purpose of this study is to investigate the possible roles of these molecules in IMPC.Methods:Primary pathologic features and lymph node metastasis status of 100 cases of IMPC were examined by microscopic analysis.Immunohistochemical analysis for the expression of E/P/L-selectin and sLe~x was performed,along with CD34 to measure microvessel density(MVD)of IMPC.97 cases of invasive ductal carcinoma not otherwise specified(IDC-NOS)were selected as control.Results:1.The percentage of IMPC components in the whole tumor was not significantly associated with lymph node metastasis rate(P=0.067)or the number of positive lymph nodes(P=0.734).2.Tumor size of IMPC was significantly larger than that of IDC-NOS(P=0.010). There was no significant difference in distribution of histological grades between the IMPC and IDC-NOS(P=0.300).The lymph node metastasis rate and the mean number of positive lymph nodes in IMPC were significantly higher than that of IDC(P=0.000).In IMPC,the tumor size and histological grade was significantly associated with the number of positive lymph nodes(P=0.001; P=0.000),though they were not correlated with the lymph node metastasis rate.3.The number of E-selectin positive vessels was greater in IMPC than that of IDC (P=0.013)and it was significantly correlated with the histological grade (P=0.005),the number of positive lymph nodes(P=0.006)and the MVD (P=0.029)of IMPC,however,there was no significant difference in E-selectin expression between the lymph node metastasis positive and negative groups (P=0.162).4.The P-selectin expression in IMPC tumor cells was higher than in IDC-NOS (P=0.000),and it was not associated with lymph node metastasis of IMPC.5.L-selectin positive lymphocytes can be found in the stroma and lymph nodes of IMPC.6.The sLe~x expression of IMPC was higher than that of IDC.(62%vs 51.5%, P=0.005),which was associated with lymph node metastasis(P=0.023).7.In IMPC,the sLe~x expression was predominantly in the stroma-facing surface of the cell clusters(basal)and the adjacent stroma,accentuating the outlines of the micropapillary units by forming a distinct band on the surface,in contrast to IDC in which sLe~x expression is largely intracytoplasmic or intercellular;No significant difference was found in respect to the sLe~x positive percentage and expression pattern between metastasis positive axillary lymph nodes and the corresponding primary tumor tissue.8.The lymph node metastasis rate of IMPC with sLe~x basal expression(97.9%, 46/47)was higher than that of sLe~x negative group(80%,28/30),P=0.005,while no significant difference was found between the intracytoplasmic or intercellular group(92.3%,12/13)and sLe~x negative group.Conclusion:1.The biological behavior of IMPC is not dependent on the percentage of IMPC components in the whole tumor.2.In IMPC,tumor size and histological grade are closely related to the extent of lymph nodes involved,but they are not specific key factors that affect lymph node metastasis in IMPC.3.E-selectin and sLe~x may play an important role in lymph node metastasis in IMPC.E-selectin may promote angiogenesis of IMPC.The expression pattern of sLe~x in IMPC suggested that the reversal of cell polarity may be as an important factor for the morphogenesis and possibly the pathogenesis,especially their higher rates of lymph node metastasis of IMPC.4.P-selectin may contribute to the malignancy of IMPC via other pathway,such as mediating hematogenous metastasis.5.Many L-selectin positive lymphocytes were observed in the stroma of IMPC, which further confirmed the lymphocytes may be immature and inactive.