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Clinicopathologic study of invasive micropapillary carcinoma of the breast.

ABSTRACT: Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast carcinoma. It is presumed to be more aggressive than invasive ductal carcinoma (IDC), though it is uncertain whether the prognoses of IMPC and IDC differ. In this retrospective study, we compared the clinicopathologic characteristics and survival between 170 female patients with IMPC (pure or mixed with IDC) and 728 with pure IDC. The IMPC patients had higher clinical stages and histologic grades, higher incidences of lymphovascular invasion and axillary lymph node extracapsular extension, and a higher degree of lymph node involvement than IDC patients. Moreover, IMPC was associated with increases in estrogen receptor (ER) and progesterone receptor (PR) positivity and HER-2 overexpression. Although locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) were poorer in IMPC patients than IDC patients, overall survival and distant metastasis survival did not differ between the two groups. Multivariate analysis revealed that IMPC was an independent prognostic factor for LRRFS in breast cancer, and IMPC patients had poorer clinicopathologic characteristics and poorer RFS and LRRFS than IDC patients. We therefore suggest that to improve treatment decisions, patients with breast carcinoma be tested for the presence of this specific subtype.

SUBMITTER: Tang SL

PROVIDER: S-EPMC5522079 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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The prognosis of invasive micropapillary carcinoma compared with invasive ductal carcinoma in the breast: a meta-analysis.

Project description:BackgroundInvasive micropapillary carcinoma (IMPC) of the breast is a rare variant of invasive ductal carcinoma (IDC). The prognosis of IMPC compared with that of IDC remains controversial; we conducted a meta-analysis to evaluate the prognostic difference between IMPC and IDC.MethodsWe searched the PubMed, Cochrane Library, and EMBASE databases for relevant studies comparing overall survival (OS), disease-specific survival (DSS), relapse-free survival (RFS), local-regional recurrence-free survival (LRRFS) or distant metastasis-free survival (DMFS) rates between IMPC and IDC. Fixed-effect and random-effect models were utilized based on the heterogeneity of the eligible studies. Heterogeneity was further evaluated by subgroup and sensitivity analyses.ResultsFourteen studies with 1888 IMPC patients were included in the meta-analysis. The summarized odds ratio (OR) and 95% confidence interval (95% CI) was calculated to estimate the prognostic difference between IMPC and IDC. IMPC patients showed an unfavorable prognosis for RFS (OR; 2.04; 95% CI: 1.63-2.55) and LRRFS (OR: 2.82; 95% CI: 1.90-4.17) compared with IDC. However, no significant difference was observed in OS (OR: 0.93; 95% CI: 0.78-1.10), DSS (OR: 1.16; 95% CI: 0.95-1.40) and DMFS (OR: 0.95; 95% CI: 0.67-1.35) between IMPC and IDC. No obvious statistical heterogeneity was detected, except for DSS. Funnel plots and Egger's tests did not reveal publication bias, except for RFS.ConclusionsThis analysis showed that IMPC patients have a higher rate of loco-regional recurrence than IDC patients. However, OS, DSS and DMFS were not significantly different between IMPC and IDC. These results could help clinicians select therapeutic and follow-up strategies for IMPC patients.

| S-EPMC5725780 | biostudies-literature

Population-based comparison of prognostic factors in invasive micropapillary and invasive ductal carcinoma of the breast.

Project description:BackgroundInvasive micropapillary carcinoma (IMPC) is a variant of breast carcinoma with a higher propensity for lymph node metastases compared with invasive ductal carcinoma (IDC).MethodsRetrospective analysis of 636 IMPC and 297 735 IDC cases in the Surveillance, Epidemiology and End RESULTS database comparing disease-specific survival (DSS) and overall survival (OS) between IMPC and IDC.ResultsA higher percentage of IMPC cases (52.0%) had nodal metastases compared with IDC cases (34.6%). The 5-year DSS and OS for IMPC was 91.8% and 82.9%, respectively compared with 88.6% and 80.5% for IDC, respectively. For both IMPC and IDC, oestrogen-receptor positivity was associated with better survival, while having four or more positive lymph nodes or larger tumour size correlated with worse survival. Radiotherapy provided a survival benefit for both histological types.ConclusionsDespite IMPC's higher propensity for lymph node metastasis, IMPC has DSS and OS that compare favourably with IDC.

| S-EPMC4119976 | biostudies-literature

Spatial transcriptomics reveals gene expression characteristics in invasive micropapillary carcinoma of the breast.

Project description:Invasive micropapillary carcinoma (IMPC) is a special histological subtype of breast cancer, featured with extremely high rates of lymphovascular invasion and lymph node metastasis. Based on a previous series of studies, our team proposed the hypothesis of "clustered metastasis of IMPC tumor cells". However, the transcriptomics characteristics underlying its metastasis are unknown, especially in spatial transcriptomics (ST). In this paper, we perform ST sequencing on four freshly frozen IMPC samples. We draw the transcriptomic maps of IMPC for the first time and reveal its extensive heterogeneity, associated with metabolic reprogramming. We also find that IMPC subpopulations with abnormal metabolism are arranged in different spatial areas, and higher levels of lipid metabolism are observed in all IMPC hierarchical clusters. Moreover, we find that the stromal regions show varieties of gene expression programs, and this difference depends on their distance from IMPC regions. Furthermore, a total of seven IMPC hierarchical clusters of four samples share a common higher expression level of the SREBF1 gene. Immunohistochemistry results further show that high SREBF1 protein expression is associated with lymph node metastasis and poor survival in IMPC patients. Together, these findings provide a valuable resource for exploring the inter- and intra-tumoral heterogeneity of IMPC and identify a new marker, SREBF1, which may facilitate accurate diagnosis and treatment of this disease.

| S-EPMC8605000 | biostudies-literature

Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast.

Project description:Invasive micropapillary carcinoma (IMPC) has very high rates of lymphovascular invasion and lymph node metastasis and has been reported in several organs. However, the genomic mechanisms underlying its metastasis are unclear. Here, we perform whole-genome sequencing of tumor cell clusters from primary IMPC and paired axillary lymph node metastases. Cell clusters in multiple lymph node foci arise from a single subclone of the primary tumor. We find evidence that the monoclonal metastatic ancestor in primary IMPC shares high frequency copy-number loss of PRDM16 and IGSF9 and the copy number gain of ALDH2. Immunohistochemistry analysis further shows that low expression of IGSF9 and PRDM16 and high expression of ALDH2 are associated with lymph node metastasis and poor survival of patients with IMPC. We expect these genomic and evolutionary profiles to contribute to the accurate diagnosis of IMPC.

| S-EPMC8748639 | biostudies-literature

Clinico-pathological features and prognosis of invasive micropapillary carcinoma compared to invasive ductal carcinoma: a population-based study from China.

Project description:BackgroundInvasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer that is associated with a high incidence of regional lymph node metastases and a poor clinical outcome. However, the clinico-pathological features and prognostic factors of IMPC are not well understood.Patients and methodsA total of 188 IMPC cases and 1,289 invasive ductal carcinoma (IDC) cases were included. The clinical features, breast cancer-specific survival (BCSS) and recurrence/metastasis-free survival (RFS) of the patients were compared between these two groups.ResultsThe IMPC patients exhibited more features of aggressive carcinoma than the IDC patients, including larger tumor size, higher tumor stage, a greater proportion of nodal involvement and an increased incidence of lymphovascular invasion. Patients with IMPC had lower 5-year BCSS and RFS rates (75.9% and 67.1%, respectively) than patients with IDC (89.5% and 84.5%, respectively). Compared to IDC patients, the patients with IMPC had a significantly higher percentage of stage III breast cancer (51.3% versus 21.7%). In a stage-matched Kaplan-Meier analysis, the patients with stage III IMPC had lower 5-year BCSS and RFS rates than patients with stage III IDC (BCSS, P?=?0.004; RFS, P?=?0.034). A multivariate analysis revealed that TNM stage was an independent prognostic factor for patients with IMPC. The proportion of cancers with a luminal-like subtype was significantly higher in IMPC than in IDC (P<0.001). However, after matching by molecular subtype, the patients with IMPC had significantly worse clinical outcomes than patients with IDC.ConclusionsIn Chinese women, IMPCs displayed more aggressive behaviors than IDCs, resulting in poorer clinical outcomes for patients with IMPC, regardless of a favorable molecular subtype. Our findings illustrate that the poorer survival of patients with IMPC might be due to an increased incidence and aggressiveness of tumors in TNM stage III.

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High Expression of Plakoglobin Promotes Metastasis in Invasive Micropapillary Carcinoma of the Breast via Tumor Cluster Formation.

Project description:Invasive micropapillary carcinoma of the breast (IMPC) is a rare subtype of breast cancer that has a high frequency of lymph node (LN) involvement and metastasis to distant organs. IMPC is characterized by distinct histomorphology and unfavorable prognosis when compared with invasive ductal carcinoma no special type (IDC-NST). However, the underlying molecular mechanisms remain unclear. We reported here that plakoglobin, as a key component in cell adhesion, can promote collective metastasis through facilitating IMPC clusters formation. In comparing the clinicopathological features of 451 IMPC patients and 282 IDC-NST patients, our results showed that tumor emboli were significantly higher in IMPC patients and were associated with a high frequency of metastasis. Both in vitro and in vivo data showed overexpression of plakoglobin in both the cell membrane and the cytoplasm of IMPC clusters. When plakoglobin was knocked down in IMPC cell models, the tumor cell clusters were depolymerized. Using mouse models, we validated the metastatic potential of tumor clusters was higher than single cells in vivo. Further analysis showed that higher expression of plakoglobin was able to promote activation of the PI3K/Akt/Bcl-2 pathway, which might protect the clusters from anoikis. Our data indicate that plakoglobin promotes tumor cluster formation in IMPC and downregulates apoptosis in the cell clusters through activation of PI3K/Akt/Bcl-2 signaling. These results provide a convincing rationale for the high metastatic propensity seen in IMPC.

| S-EPMC6584935 | biostudies-literature

Micropapillary variant of mucinous carcinoma of the breast shows genetic alterations intermediate between those of mucinous carcinoma and micropapillary carcinoma.

Project description:AimsMicropapillary variant of mucinous carcinoma of the breast (MPMC) is a rare histological form of oestrogen receptor (ER)-positive invasive carcinoma that is characterised by micropapillary clusters of tumour cells in lakes of extracellular mucin. The aims of this study were to determine the genetic alterations underpinning MPMCs, and to determine whether they overlap with those of mucinous carcinomas and/or invasive micropapillary carcinomas.Methods and resultsDNA from five MPMCs was subjected to whole-exome sequencing. Somatic mutations, copy number alterations and mutational signatures were determined with state-of-the-art bioinformatics methods. No mutations in genes significantly mutated in breast cancer, including TP53, PIK3CA, GATA3, and MAP3K1, were detected. We identified copy number alterations that have been reported in invasive micropapillary carcinomas, such as recurrent gains in 1q, 6p, 8q, and 10q, and recurrent losses in 16q, 11q, and 13q, as well as a recurrent 8p12-8p11.2 amplification encompassing FGFR1. Like mucinous carcinomas, three of the five MPMCs analysed lacked PIK3CA mutations, 1q gains, and 16q losses, which are the hallmark genetic alterations of ER-positive breast cancers, whereas two MPMCs harboured 16q losses and/or a complex pattern of copy number alterations similar to those found in breast-invasive micropapillary carcinomas.ConclusionsMPMCs are heterogeneous at the genetic level; some tumours show a pattern of somatic genetic alterations similar to those of mucinous carcinomas, whereas others resemble invasive micropapillary carcinomas at the genetic level. These findings suggest that MPMCs may not constitute one histological subtype, but rather a convergent phenotype that can stem from mucinous carcinomas or invasive micropapillary carcinomas.

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Laser-capture microdissected invasive micropapillary carcinomas of the breast

Project description:The purpose of this study was to identify differentially expressed genes in laser-capture microdissected (LCM) invasive mammary carcinomas (IMCs).

2011-04-25 | GSE28821 | GEO

Laser-capture microdissected invasive micropapillary carcinomas of the breast

Project description:The purpose of this study was to identify differentially expressed genes in laser-capture microdissected (LCM) invasive mammary carcinomas (IMCs). Invasive mammary carcinoma of the breast surgical resection specimens were laser capture microdissected for RNA extraction and hybridization to Affymetrix microarrays.

| S-ECPF-GEOD-28821 | biostudies-other

Laser-capture microdissected invasive micropapillary carcinomas of the breast

2011-04-25 | E-GEOD-28821 | biostudies-arrayexpress