1: Am J Clin Pathol. 2006 Nov;126(5):740-6

Invasive micropapillary carcinoma of the breast: association of pathologic features with lymph node metastasis.

Guo X, Chen L, Lang R, Fan Y, Zhang X, Fu L.

Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Hospital of Tianjin Medical University, Tianjin, China.

Invasive micropapillary carcinoma (IMPC) of the breast is characterized by a high incidence of axillary lymph node metastasis. To investigate the relationship between pathologic features and lymph node metastasis, 51 cases of breast carcinoma with IMPC components were studied. Immunohistochemical analysis for vascular endothelial growth factor (VEGF)-C and VEGF receptor (VEGFR)-3 was performed, and lymphatic vessel density was measured. The main findings included a significantly increased number of positive lymph nodes and/or an increased rate of lymph node metastasis in IMPC with a higher histologic grade, prominent stromal infiltration of lymphocytes, and higher VEGF-C expression and lymphatic vessel density. The percentage of IMPC component in the tumor was not associated with the incidence of lymph node metastasis. The results suggest that the histologic grade, lymphatic vessel density, and lymphocyte infiltration of IMPC are the key factors that influence lymph node metastasis. Further studies are required to elucidate the mechanisms underlying the lymphotropism of this distinct variant of breast carcinoma.

2: Breast Cancer. 2006;13(1):58-63

The reversed apical pattern of MUC1 expression is characteristics of invasive micropapillary carcinoma of the breast.

Li YS, Kaneko M, Sakamoto DG, Takeshima Y, Inai K.

Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a special subtype of invasive ductal carcinoma (IDC), which is known to have a high potential to metastasize to the axillary lymph node. However, it is sometimes difficult to differentiate IMPC from conventional IDC showing an IMPC-like pattern due to artifact (pseudo-IMPC). In the present study, we investigated the usefulness of immunohistochemical expression of MUC1 for distinguishing IMPC from pseudo-IMPC, and analyzed several clinicopathological parameters of IMPC and pseudo-IMPC cases. METHODS: Eighty cases showing IMPC or IMPC-like pattern were selected from our surgical files of 1,240 cases of IDC. We examined the expression of MUC1, D2-40 and CD34 by immunohistochemistry. RESULTS: Eighty cases were classified into 9 cases (0.7%) of pure-IMPC, 31 cases (2.5%) of mixed-IMPC, and 40 cases of pseudo-IMPC, according to the expression pattern of MUC1. In pure-IMPC cases, MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters, while in pseudo-IMPC, MUC1 expression was present in the whole cytoplasmic membrane and/or cytoplasm. There were no significant differences among the three groups in patient age, tumor size and nuclear grade of neoplastic cells. However, lymphatic invasion and lymph node metastasis in the pure-IMPC or mixed-IMPC cases were higher than those in pseudo-IMPC cases with statistically significant values. Pure-IMPC has a higher recurrence rate and lower overall survival compared to pseudo-IMPC [P = 0.0165(DFS) P = 0.025(OS)]. CONCLUSIONS: This study demonstrated that immunohistochemistry of MUC1 is useful for the diagnosis of IMPC. The pure-IMPC cases had higher incidences of lymphatic invasion and lymph node metastasis, and also showed a poorer prognosis.

3: Breast Cancer Res Treat. 2005 Dec;94(3):225-35

N-cadherin expression in breast cancer: correlation with an aggressive histologic variant--invasive micropapillary carcinoma.

Nagi C, Guttman M, Jaffer S, Qiao R, Keren R, Triana A, Li M, Godbold J, Bleiweiss IJ, Hazan RB.

Department of Pathology, Mount Sinai School of Medicine, New York, NY, USA.

Upregulation of N-cadherin in epithelial tumor cells has been shown to contribute to the invasive/metastatic phenotype. It remains however to be determined whether N-cadherin is increased in human breast cancers with enhanced malignant potential. We examined a large number of invasive breast cancer specimens (n = 114) for N- and E-cadherin. These specimens compared invasive duct carcinomas (IDCs) of varying histologic grades with an aggressive subtype, invasive micropapillary carcinoma of the breast (MPAP), which has a high propensity for lymphatic invasion and lymph node metastasis. Staining scores for N- and E-cadherin were compared between non-MPAP and MPAP IDCs, and between the invasive and ductal carcinoma in situ (DCIS) of each IDC using statistical analysis. We found that N-cadherin was expressed in 76% of MPAP and 52% of non-MPAP carcinomas, and E-cadherin in 57% of MPAP and 36% of non-MPAP tumors. More MPAP (25%) compared to non-MPAP (5%) tumors expressed both cadherins. Of the two cadherins, N-cadherin was significantly associated with MPAP tumors (p = 0.033) compared to E-cad (p = 0.171). Moreover, in the majority of tumors that were positive for N-cadherin, the staining scores were increased in the IDC relative to intraductal components, and this effect was more dramatic in the MPAP carcinomas. This difference for N-cadherin was greater than the corresponding difference for E-cadherin in the MPAP group (p = 0.005), whereas such changes were not significant in the non-MPAP group (p = 0.10). Thus, N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression.

4: Arch Pathol Lab Med. 2005 Oct;129(10):1277-82.

Immunohistochemical and clinicopathologic characteristics of invasive ductal carcinoma of breast with micropapillary carcinoma component.

Kim MJ, Gong G, Joo HJ, Ahn SH, Ro JY.

Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

CONTEXT: A micropapillary carcinoma (MC) component is generally considered to behave aggressively. Although several reports have described the prognostic significance of MC in breast carcinomas, immunohistochemical findings of MC, especially as compared to non-MC, are rarely described. OBJECTIVE: We compared clinicopathologic and immunohistochemical findings between 38 cases of invasive breast carcinoma with an MC component (IMC) and 217 cases of invasive breast carcinoma without an MC component (NIMC). DESIGN: We constructed a tissue microarray from 38 cases of IMC and performed immunohistochemical stainings for cytokeratin (CK) 7, CK20, estrogen receptor, progesterone receptor, p53, c-Erb-B2, CD34, CK5, epidermal growth factor receptor, and c-Kit in both MC and non-MC components. RESULTS: Cases with IMC were associated with greater tumor size, more frequent lymphovascular invasion, nodal metastases, greater mean numbers of positive lymph nodes, and higher stage than those with NIMC, but were not associated with poorer survival rates. On immunohistochemistry, only p53 reactivity was statistically different between MC and non-MC components in IMC cases. Estrogen receptor positivity tended to be lower in MC than non-MC, but the difference was not significant. Most of the MCs and non-MCs in IMC cases were positive for CK7, but none of them were positive for CK20, CK5, epidermal growth factor receptor, or c-Kit. CONCLUSIONS: Based on the frequent nodal metastases and association with higher stage found in IMC as compared with NIMC cases, as well as higher p53 positivity and lower frequency of estrogen receptor expression, MC could be considered an aggressive histologic type of breast carcinoma. In both MC and non-MC components in IMC cases, no basallike immunostaining pattern was detected