Invasive Ductal Carcinoma-not Otherwise Specified Research Articles

Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis

Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.

Evaluation of Lymph Node Metastasis in Invasive Micropapillary Breast Carcinoma and Other Its Related Variables

Background: The rate of lymph node metastasis in patients with invasive micropapillary carcinoma (IMPC) could be considered a critical prognostic factor whose measurement may enhance therapeutic outcomes in these patients. Objectives: The current study aims at determining the rate of lymph node involvement in IMPC patients and comparing it with that of invasive ductal carcinoma, not otherwise specified (IDC-NOS) patients. Methods: In this case-control study, a total of 124 participated, including 61 patients with IMPC and 63 patients with IDC-NOS. The rate of lymph node metastasis and its possible connection with the patient's age, tumor size, grade and focality, lymphovascular invasion, and proportion of micropapillary component were determined in patients with IMPC and compared to that of IDC-NOS patients. Results: Lymph node involvement was detected in 80.3% of patients with IMPC, which is significantly higher compared to patients with IDC-NOS. No significant correlation was found between lymph node metastasis and the patients’ age, tumor size, and focality in both IMPC and IDC-NOS groups. Furthermore, no significant relationship was observed between lymph node metastasis and tumor grade in IMPC, while metastasis to lymph nodes was directly correlated with higher tumor grades of NOS type. Moreover, in both types of cancer, lymph node metastasis was significantly associated with lymphovascular invasion. In patients with IMPC, no statistically significant relevance was observed between lymph node metastasis and the percentage of micropapillary components. Conclusions: According to the results of this study, patients with IMPC had a significantly higher rate of lymph node involvement compared to IDC-NOS. Hence, the rate of lymph node involvement could be used as a prognostic factor in these patients.

Correlation of immunohistochemistry markers in breast carcinoma with biological characteristics and tumor grade as histopathological prognostic parameters

Background: Prognosis of breast cancer and success of therapeutic interventions largely rely on clinico-pathologic and biological characteristics of tumor and vary due to the heterogenous nature of breast cancers. This study was intended to find correlation between the expression of Estrogen receptor (ER), Progesterone receptor (PR) and Human Epidermal Growth Factor Receptor-2 (HER-2/neu) with histological grade in case of carcinoma of breast. Material and Method: This study was conducted on 56 histologically confirmed specimens of breast carcinoma in Department of Pathology, Surat Municipal Institute of Medical Education and Research. Results: Maximum number of cases of breast carcinoma were found in 41-50 years aged females. Invasive ductal carcinoma-not otherwise specified (IDC-NOS) (82.14%) was most common histological type. Most of the carcinoma showed grade II (62.5%). ER, PR and HER-2/neu positivity was 50%, 42.86% and 42.86% respectively. Conclusion: Evaluation of ER, PR and HER-2/neu status and tumor grade should be incorporated routinely as a part of histopathological reports in all cases of breast carcinoma as they not only help in histopathologic assessment of prognosis, but also help in deciding the management thereby improving overall survival.

SLex expression in invasive micropapillary breast carcinoma is associated with poor prognosis and can be combined with MUC1/EMA as a supplementary diagnostic indicator.

Objective:Mucin 1 (MUC1/EMA) and sialyl Lewis X (sLex) indicate polarity reversal in invasive micropapillary carcinoma (IMPC). The purpose of this study was to evaluate the expression of MUC1/EMA and sLex and to assess their diagnostic and prognostic value in patients with IMPC.Methods:The expression of sLex and MUC1/EMA in 100 patients with IMPC and a control group of 89 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) were analyzed with IHC. Fresh tumor tissues were collected from patients with IMPC or IDC-NOS for primary culture and immunofluorescence analysis.Results:The rate of nodal metastasis was higher in patients with IMPC than those with IDC-NOS, and IMPC cells tended to express more sLex and MUC1/EMA in the cytomembranes (the stroma-facing surfaces of the micropapillary clusters) than IDC-NOS cells. In IMPC, high cytomembrane expression of sLex, but not MUC1/EMA, indicated poor prognosis. In addition, among the 100 patients with IMPC, 10 patients had sLex+/EMA– expression patterns, and 8 patients had sLex–/EMA+ expression patterns. The primary IMPC cells were suspended, non-adherent tumor cell clusters, whereas the primary IDC cells were adherent tumor cells. Immunofluorescence analysis showed that MUC1/EMA and sLex were co-expressed on the cytomembranes in IMPC cell clusters and in the cytoplasm in IDC-NOS cells.Conclusions:sLex can be used as a prognostic indicator and can be combined with MUC1/EMA as a complementary diagnostic indicator to avoid missed IMPC diagnosis.

Therapy-induced histopathological changes in breast cancers: The changing role of pathology in breast cancer diagnosis and treatment

Aim: Breast cancer therapy causes morphological alterations in the cancerous as well as the surrounding healthy tissue. The histopathological interpretation in such cases, thus, requires a thorough knowledge of the cytological and stromal changes rendered by the therapy during and posttherapy. The aim of the present study was to evaluate such cytological and stromal changes rendered by the therapy in breast cancer cases. Methods: The present study was a combined retrospective and prospective study, wherein clinical and histopathological details were collected from a total of 39 cases of breast carcinoma before and posttherapy, and the changes induced by the therapy were correlated. Results: Stage II breast carcinoma was found to be the most predominant stage, while invasive ductal carcinoma-not otherwise specified (IDC-NOS) of tumor was the most common histologic type both before (94.87%) and after (76.92%) therapy. Pathologic complete response (pCR) was observed in 18% of the cases while 15% showed pathologic partial response (pPR) and 66.7% cases had a stable disease. Intracellular changes commonly noted after chemotherapy included nuclear enlargement, hyperchromasia, and increased nuclear: cytoplasmic ratio while predominant stromal changes included necrosis (74.4%), fibrosis (64.1%), and desmoplasia (59%). Conclusion: Breast cancer therapy causes morphological alterations in the cancerous as well as the surrounding healthy tissue. The histopathological interpretation in such cases, thus, requires a thorough knowledge of the cytological and stromal changes rendered by the therapy.

HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.

Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma-not otherwise specified (IDC-NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC-NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC-NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC-NOS were detected using immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1-positive, and 100 out of 148 (67.6%) were ER-positive. Of the latter, 28% (28/100) were HPK1-positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=−0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC-NOS tissues were PR- or HER2-positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor-node-metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER-positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC-NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC-NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.

Absence of caveolin-1 expression in carcinoma-associated fibroblasts of invasive micropapillary carcinoma of the breast predicts poor patient outcome.

Caveolin-1 (Cav-1) expression in stromal carcinoma-associated fibroblasts (CAFs) has been associated with tumor progression and clinical outcome. This study was undertaken to assess its prognostic significance in invasive micropapillary carcinoma of the breast (IMPC), a tumor with abundant stromal CAFs and a high tendency for nodal metastasis and poor outcome. Cav-1 expression was studied by immunohistochemistry in a group of 86 cases of IMPC along with a control group of 105 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). Our results indicate that absence of Cav-1 expression in CAFs of IMPC is more common than in IDC-NOS (57 %, 49/86 vs. 36 %, 38/105). The absence of expression was associated with larger tumor size and higher lymph node stage (P < 0.05) of IMPC. Univariate analysis suggested absence of Cav-1 in CAFs to be a candidate independent predictor of reduced progression-free survival (PFS) (HR = 3.945, 95 % CI = 1.717-9.063, P = 0.001), which was confirmed by multivariable analysis (P = 0.018). In patients with IMPC spreading to local lymph nodes, loss of stromal Cav-1 predicted a fourfold increase in risk for shortened PFS. In contrast, no significant difference of tumor epithelial Cav-1 expression was found between IMPC and IDC-NOS, and the expression of tumor Cav-1 was not significantly associated with the prognosis of patients with IMPC. Absence of Cav-1 expression in CAFs is a strong prognostic factor for IMPC patients, and it may further subgroup the patients with lymph node metastasis to guide clinical management.

Cytoplasmic expression of aquaporin-1 in breast cancer cells and its relationship with clinicopathological characteristics and prognosis

To detect the expression of aquaporin 1 (AQP1) in breast cancer tissues, and to analyze its relationship with clinicopathological characteristics and prognosis of breast cancer patients. Histochemical SP staining was used to assess the AQP1 expression in 30 cases of lobular hyperplasia of mammary gland, 16 cases of ductal carcinoma in situ (DCIS), and 78 cases of invasive ductal carcinoma-not otherwise specified (IDC-NOS), and to analyze the relationship between cytoplasmic expression of AQP1 in IDC-NOS and clinical pathological characteristics and prognosis of the patients. Positive AQP1 immunolabelling appeared as brown deposit over the membrane of myoepithelial cells in all cases of lobular hyperplasia of mammary gland, but only 10.0% of cases showed cytoplasmic staining in glandular epithelial cells. In the ductal carcinoma in situ, brown deposit of AQP1 immunolabelling appeared over the myoepithelial cell membrane in all cases, but only 12.5% of cases were accompanied with cytoplasmic staining in glandular epithelial cells. In the invasive ductal carcinoma not otherwise specified, 35.9% of the cases showed cytoplasmic AQP1 immunoreactivity, but only 3.8% of cases showed positive membrane staining of the tumor cells. There were highly positive AQP1 expression in 14 cases, weakly positive in 14 cases, and negative in 50 cases. Cytoplasmic AQP1 expression in the IDC-NOS cases was significantly correlated with pathologic stage, PR, HER-2, lymph node status, Nottingham prognostic index (NPI) and metastasis or recurrence (all P < 0.05). The 5-year progression-free survival (PFS) rates were 16.8% in the patients with strong positive AQP1 expression, 90.9% in the cases with weakly positive AQP1 expression and 94.9% in the AQP1-negative cases, showing a significant difference (P < 0.05). Multivariate analysis indicated that the lymph node status and cytoplasmic expression of AQP1 were independent factors for PFS (both P < 0.05). The 5-year overall survival (OS) rates were 45.6% in the AQP1- strong positive cases, 90.0% in the AQP1-weakly positive cases and 97.7% in the AQP1-negative cases, showing a significant difference (P < 0.05). Multivariate analysis indicated that the lymph node status and cytoplasmic expression of AQP1 were independent factors affecting the overall survival and progression-free survival (both P < 0.05). AQP1 is mainly expressed on the membrane of myoepithelial cells in the benign breast lesions, but in the cytoplasm of breast cancer cells, and its expression is an independent factor affecting prognosis of breast cancer patients.

The prognostic value of tumor budding in invasive breast cancer

We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&E slides with a maximal invasive margin in a 0.950mm2 field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0–7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (P<0.001). By immunohistochemical staining, budded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, P<0.001) together with tumor size (HR 2.468, P=0.002), node status (HR 2.362, P<0.001), and LVI status (HR 1.910, P=0.035) was the independent prognostic factor in IDC-NOS. In conclusion, tumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS.

Phenotypic Drift as a Cause for Intratumoral Morphological Heterogeneity of Invasive Ductal Breast Carcinoma Not Otherwise Specified

Invasive ductal carcinoma (IDC) not otherwise specified (NOS), the most common type of breast cancer, demonstrates great intratumoral morphological heterogeneity, which encompasses the presence of different types of morphological structures—tubular, trabecular, solid, and alveolar structures and discrete groups of tumor cells, the origins of which remain unclear at present. In this study of 162 IDC NOS patients, we investigated whether the distribution of different types of morphological structures is related to the basic clinicopathological parameters of IDC NOS. Our results showed that in patients with only one type of tumor structure, the presence of any one of the five types was equally probable; however, cases with two types of structures were more likely to contain trabecular structures than the other four types. The development of intratumoral morphological heterogeneity was not associated with menopausal status, tumor size, histological grade, hematogenic metastasis, or recurrence. However, the number of different types of morphological structures was significantly higher in luminal tumors than in triple-negative tumors. An increase in the frequency of lymph node metastasis correlated with the increased number of different types of structures in breast tumors; however, in contrast to premenopausal patients, this association was explained by the presence of alveolar structures in postmenopausal women. In addition, we showed a significant decrease in the numbers of positive lymph nodes in tumors with high numbers of morphological variants. The frequency of lymph node metastases and the number of positive nodes were generally independent features and formed by different mechanisms. Based on the evidence, the term “phenotypic drift” has been designated as the basis for the development of intratumoral morphological heterogeneity of IDC NOS.

The differences in the histological types of breast cancer and the response to neoadjuvant chemotherapy: The relationship between the outcome and the clinicopathological characteristics

Although effective regimens have been established for invasive ductal carcinoma-not otherwise specified (IDC), the efficacy and prognosis of other minor types of breast cancer are unknown because of their rareness. The clinicopathological features and prognosis of other minor types concerning the response to neoadjuvant chemotherapy (NAC) were evaluated in this study.A total of 562 patients were classified according to the Japanese and the World Health Organization (WHO) classifications, and the number of IDC and other special types (SP) was 500 and 62. The SP patients had a significantly poorer clinicopathological response to NAC and less breast-conservative therapy than those with IDC. According to the WHO classification, mucinous carcinoma, metaplastic carcinomas and apocrine carcinoma also responded poorly, and patients with metaplastic carcinomas and invasive lobular carcinoma had a significantly poorer prognosis. Despite the poor response to chemotherapy, patients with mucinous carcinoma and apocrine carcinoma had a good prognosis.The response to NAC and the prognosis vary for each histological type. For some types, the prognosis was not related to the clinicopathological response to NAC. BackgroundIn the treatment of breast cancer, neoadjuvant chemotherapy (NAC) has become the standard treatment modality for downstaging purposes. Although effective regimens have been established for the treatment of invasive ductal carcinoma-not otherwise specified (IDC), the data about the efficacy and prognosis for patients with other minor types of breast cancer are insufficient because of the rareness of these tumors. Defining the relationship between each histological type and the clinicopathological response to NAC is essential to optimizing individualized treatment. MethodsWe retrospectively evaluated the clinicopathological features and classification of the histological types based on the Japanese and the World Health Organization (WHO) classifications before and after NAC in 562 patients with primary breast cancer who underwent curative treatment after NAC between 1998 and 2008. The prognosis was estimated for each histological type. ResultsOf the 562 patients, the number of cases of IDC and other special types (SP) was 500 and 62. In the SP group, the clinicopathological response to NAC was significantly poorer, and the patients underwent breast-conservative therapy less frequently than did the IDC patients. According to the WHO classification, mucinous carcinoma, metaplastic carcinomas and apocrine carcinoma responded poorly to NAC. The disease-free survival and overall survival were significantly worse for patients with metaplastic carcinomas (p < 0.001 and p < 0.001) and with invasive lobular carcinoma (p = 0.03 and p < 0.001) than other cancers. Despite their poor response to treatment, patients with mucinous carcinoma and apocrine carcinoma had a good prognosis. ConclusionsThe response to standardized NAC and prognosis varies for each histological type. For some types, the prognosis was not associated with the clinicopathological response to NAC. Innovative regimens should therefore be investigated for each histological type to achieve the best response.

Does apoptosis contribute to a relatively better prognosis in medullary carcinoma of breast?

Background and Aims: Apoptosis (programmed cell death) is considered to play a critical role in tumor genesis, where a down regulation of the process contributes to development and progress of neoplasia. Medullary carcinoma (MC) of breast has generally been considered to have a better prognosis than invasive ductal carcinoma not otherwise specified (IDCC-NOS), which would seem to be discrepant when one considers its anaplastic histology and high mitotic rate. We, hence, attempted to elucidate the importance and implications of apoptosis in the prognosis of medullary carcinoma of breast. Materials and Methods: Formalin-fixed, paraffin-embedded sections of 30 cases of medullary carcinoma of breast and 30 cases of IDCC-NOS (controls) were investigated by light microscopy. Results: Mean values of apoptotic count was significantly higher in MC than in IDCC-NOS (P Conclusion: It appears that a high frequency of apoptosis may be related to a favorable prognosis in medullary carcinoma even though it demonstrates a high mitotic count with a rapid cell turnover. Since apoptotic cells can be counted with a good reproducibility in H and E stained tumor sections, the apoptotic index could possibly be used as an additional prognostic indicator in invasive breast cancer.

P5-05-02: Phenotypic Plasticity in the Normal Breast.

Abstract Background: The cell of origin of metaplastic carcinoma of the breast (MCB) is an enigma. MCB comprises less than 4% of all breast cancers, and is a member of the subtype of breast cancer referred to as Triple Negative Breast Cancer (TNBC). It is aggressive with a prognosis worse than that that for invasive ductal carcinoma NOS (not otherwise specified), as well as other TNBCs. Identification of the histogenesis of MCB is likely to provide clues to its oncogenesis. Differentiation along non-epithelial lineages is also observed in benign lesions of the breast. Adenomyoepitheliomas, thought to arise from myoepithelial cells, have been observed to contain areas of cartilaginous, sebaceous, squamous, and osseous differentiation. Methods: Healthy woman volunteers from central Indiana were invited to donate breast tissue to the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center. Starting from the 10 gauge tissue cores, 28 normal mammary epithelial (HME) and 33 normal stromal (HMS) cell lines were established using an organoid isolation method after digestion with enzymes for 24 hours. The HME cell lines were characterized by immunohistochemistry (IHC). Ploidy was determined by karyotype and Interphase FISH mapping with centromere probes for Chromosomes X and 17. Cellular morphology was observed both on two-dimensional and in three-dimensional culture systems. The HME cells were subjected to FACS analysis using multiple antibodies including CD24, CD44, Muc1, CD49f, and EpCAM. Results: 96.9% of early passage cells are diploid. The HME cells express vimentin, CK 5/6, p63, CD 10, CK 18, and HER-1 when grown on two dimensional plastic surfaces. Cells placed in the center of a sandwich of Matrigel® uniformly form spheres 37mm-325mm in diameter. Hematoxylin and eosin staining of the formalin-fixed and paraffin-embedded sections of these spheres reveal keratinized squamous differentiation. When the cells are grown on Laminin, Collagen IV, or Fibronectin surfaces multiple cell types are observed including osteoclasts, distinguished by the presence of Tartrate Resistant Acid Phospatase; and chondrocytes, confirmed by staining with Alcian Blue. Other cells with a spindle-shape and cytoplasmic vacuoles turn a dark reddish-brown color when stained with Oil Red O, characteristics of adipocytes. In other areas of the culture, the cells form a syncitium and they express the protein MyoD, a marker of immature muscle. Finally, there are numerous cells with long, dendritic processes. These cells express Nestin, a marker of neural stem cells; glial fibrillary acidic protein (GFAP), expressed by mature astrocytes; and beta-III tubulin produced by differentiated neurons. Using FACS, the HME cells were found to be CD49f positive and EpCAM negative. Multiple nucleoli were confirmed using anti-Nucleostemin IHC. Conclusions: Phenotypic plasticity is common to all the HME cell lines characterized to date. Differentiation into cells of mesodermal and ectodermal origin, CD49+/EpCAM- by FACS, and the presence of multiple nucleoli suggest that the isolated cells are a multipotent/stem cell residing in the normal adult breast. These cells, through a series of yet to be elucidated events, may be the cells of origin of MCB. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-05-02.

Increased expression of CD146 and microvessel density (MVD) in invasive micropapillary carcinoma of the breast: Comparative study with invasive ductal carcinoma-not otherwise specified

Invasive micropapillary carcinoma (IMPC) is a rare variant of ductal carcinoma of the breast, and is characterized by a high metastatic potential and an aggressive clinical course. Studies of CD146 expression and function in breast cancer remain scarce. The aim of this study was to evaluate the role of CD146 and microvessel density (MVD) in breast IMPC. CD146 mRNA expression and immunohistochemistry for CD146 and MVD measured by CD31 were assessed in 82 cases of IMPC and 137 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The mRNA level of CD146 in cancer specimens was higher in IMPC than in IDC-NOS. CD146 expression in tumor cells was up-regulated in IMPC as compared with that in IDC-NOS, and was positively correlated with histological grade, ER, PR status, and P53 expression in IMPC and IDC-NOS. CD146 expression in vascular endothelial cells was significantly higher than that in IDC, and was positively correlated with tumor progression in IMPC and IDC-NOS. MVD in IMPC was significantly higher than that in IDC. CD146 expression in tumor cells was positively correlated with that in vascular endothelial cells of IMPC and IDC-NOS. The association of CD146 expression with MVD and its correlation with progression in breast carcinoma indicated that CD146 is a potentially useful prognostic marker for breast cancer. CD146 could be a new drug target in the treatment of breast cancer.

PSCA expression in invasive micropapillary carcinoma of breast

To study the expression of prostate stem cell antigen (PSCA) at protein and mRNA levels in invasive micropapillary carcinoma of the breast (IMPC) and to analyze the relationship between PSCA expression and clinicopathologic features. The expression of PSCA protein was analyzed by immunohistochemistry (LSAB) in 66 cases of IMPC and 67 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The association between PSCA expression and clinicopathologic features was also analyzed in IMPC. Furthermore, RT-PCR was used to detect PSCA mRNA in 10 cases of primary IMPC and 10 cases of primary IDC-NOS with paired normal breast tissues, each from the same subject. Immunohistochemical analysis revealed the overexpression of PSCA in 47 of 66 (71.2%) cases of IMPC and 35 of 67 (52.2%) IDC-NOS. Statistical analysis showed a significant difference of PSCA expression between IMPC and IDC-NOS (P = 0.024). In IMPC, the expression of PSCA was correlated with lymph nodes metastasis (P = 0.039). RT-PCR showed the mRNA level of PSCA was significantly higher in primary IMPC and IDC-NOS tissue than that in paired normal breast tissue (7/10 and 5/10, respectively), and it was also significantly higher in primary IMPC tissue than that in IDC-NOS tissue. PSCA might play an important role in lymph node metastasis in IMPC.

Mucinous Carcinoma of the Breast in Comparison with Invasive Ductal Carcinoma: Clinicopathologic Characteristics and Prognosis

PurposeMucinous carcinoma (MC) of the breast is a rare histologic type of mammary neoplasm. The objective of this study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) of MC.MethodsWe conducted a retrospective analysis of all MC cases reported to a database between 1994 and 2010. Clinicopathological characteristics and survival of 268 MC cases were reviewed and compared with 2,455 invasive ductal carcinoma-not otherwise specified (IDC-NOS) cases.ResultsThe MC cases were of a younger age, involved less lymph nodes, lower stage, more expression of hormonal receptors, and less HER2 overexpression compared to the IDC-NOS cases. The 5-year DFS rate for MC was 95.2% compared to 92.0% for IDC-NOS. The 5-year OS rate for MC was 98.9% compared to 94.9% for IDC-NOS. Multivariate analysis using Cox regression revealed that the mucinous type was a significant prognostic factor for DFS with lower nodal status (N stage) and hormonal therapy. For OS, only N stage was the most significant prognostic factor followed by adjuvant chemotherapy and adjuvant hormonal therapy.ConclusionMC was shown to be associated with a better DFS than IDC-NOS, but it had a similar OS. Nodal status and adjuvant therapy appear to be more significant predictors of prognosis than histologic subtype.

Clinicopathological Characteristics of Mucinous Carcinoma of the Breast in Korea: Comparison with Invasive Ductal Carcinoma-Not Otherwise Specified

Clinicopathological characteristics and prognostic factors of mucinous carcinoma (MC) were compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS). Clinicopathological characteristics and survivals of 104 MC patients were retrospectively reviewed and compared with those of 3,936 IDC-NOS. The median age at diagnosis was 45 yr in MC and 47 yr in IDC-NOS, respectively. The sensitivity of mammography and sonography for pure MC were 76.5% and 94.7%, respectively. MC showed favorable characteristics including less involvement of lymph node, lower stage, more expression of estrogen receptors, less HER-2 overexpression and differentiated grade, and better 10-yr disease-free survival (DFS) and overall survival (OS) (86.1% and 86.3%, respectively) than IDC-NOS (74.7% and 74.9%, respectively). Ten-year DFS of pure and mixed type was 90.2% and 68.8%, respectively. Nodal status and stage were statistically significant factors for survival. MC in Koreans showed similar features to Western populations except for a younger age of onset than in IDC-NOS. Since only pure MC showed better prognosis than IDC-NOS, it is important to differentiate mixed MC from pure MC. Middle-aged Korean women presenting breast symptoms should be examined carefully and evaluated with an appropriate diagnostic work-up because some patients present radiologically benign-like lesions.

Comparative expressed sequence hybridization reveals differential gene expression in morphological breast cancer subtypes

In this study, comparative expressed sequence hybridization (CESH) has been used to compare gene expression patterns in three morphologically different breast cancer subtypes: classic-type invasive lobular carcinoma (ILC), poorly differentiated ERBB2-negative invasive ductal carcinoma-not otherwise specified (IDC-NOS), and poorly differentiated ERBB2-positive IDC-NOS. CESH allows global detection of chromosomal regions with differential gene expression in a way similar to that of comparative genomic hybridization (CGH). Eight cases of each breast cancer subtype were included in the study. For each subtype, two pools of four cases each were constructed. CESH was used to compare both pools within the same morphological subtype, followed by a comparison of pools belonging to different subtypes. This revealed three chromosomal regions that were differentially expressed in ductal and lobular carcinomas, including relative overexpression at 8q13-q23 and 16q22, and relative underexpression at 8p21-p22. In addition, an expression signature characterized by relative overexpression at 3q24-q26.3, 14q23-31, 17q12, and 20q12-13 was identified for ERBB2-positive IDC-NOS. In summary, CESH analysis highlights chromosomal regions of differential gene expression that are associated with morphologically defined breast cancer subtypes and suggests that regions on chromosome 8 are of interest in the discrimination between ductal and lobular carcinomas. In addition, using CESH, it was possible to identify an ERBB2 expression signature, comprising four chromosomal regions with potential significance in the aggressive behaviour of ERBB2-positive IDC-NOS.