Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 14 de 14
Filter
1.
Tumour Biol ; 40(11): 1010428318815032, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30486739

ABSTRACT

Phyllodes tumors are rare biphasic breast tumors with the potential for both local recurrence and distant metastasis. The aberrant expression of B7-H3 and B7-H4 B7 molecules could be potential targets for future development of immunotherapeutic approaches. This work was undertaken to evaluate the expression of B7-H3 and B7-H4 in phyllodes tumors and assess the association with the grade and clinical behavior of phyllodes tumors. In addition, the roles of B7-H3 and B7-H4 in the regulation of tumor immune surveillance were evaluated by assessing the relationship between B7-H3/B7-H4 expression and T-cell infiltration. The messenger RNA and protein expression of B7-H3/B7-H4 were determined by RNAscope in situ hybridization and immunohistochemistry, respectively, in 101 phyllodes tumors (60 benign, 26 borderline, and 15 malignant) using a tissue microarray. Immunohistochemistry for CD3 and CD8 was also performed. B7-H3 messenger RNA and protein appeared to be concentrated mainly in the stromal compartment of phyllodes tumors. However, B7-H4 messenger RNA and protein were undetectable in the stromal compartment of phyllodes tumors. Stromal B7-H3 messenger RNA and protein expression were noted in 10 (16.7%) and 31 (51.7%) of 60 benign phyllodes tumors, 12 (46.1%) and 20 (76.9%) of 26 borderline phyllodes tumors, and 10 (66.7%) and 13 (86.7%) of 15 malignant phyllodes tumors, respectively. Stromal B7-H3 messenger RNA and protein expression increased as phyllodes tumors progressed from benign to borderline and finally to the malignant grade (Pearson's R = 0.411, p < 0.001 and Pearson's R = 0.293, p = 0.003, respectively). The recurrence rate was higher in the stromal B7-H3 messenger RNA or protein-positive group than in the negative group, but this difference was not significant. Stromal B7-H3 protein expression inversely correlated with the densities of CD3+ and CD8+ T-cell infiltrates ( p = 0.001 and p = 0.027, respectively). These results suggest that B7-H3 is involved in the progression of phyllodes tumors and may contribute to their immune surveillance.


Subject(s)
B7 Antigens/metabolism , Breast Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating/immunology , Phyllodes Tumor/pathology , RNA, Neoplasm/genetics , T-Lymphocytes/immunology , V-Set Domain-Containing T-Cell Activation Inhibitor 1/metabolism , Adult , B7 Antigens/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/metabolism , Case-Control Studies , Disease Progression , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization , Middle Aged , Phyllodes Tumor/genetics , Phyllodes Tumor/immunology , Phyllodes Tumor/metabolism , Prognosis , Tissue Array Analysis , V-Set Domain-Containing T-Cell Activation Inhibitor 1/genetics
2.
Cancer Res ; 77(13): 3605-3618, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28512246

ABSTRACT

Myofibroblast differentiation plays an important role in the malignant progression of phyllodes tumor, a fast-growing neoplasm derived from periductal stromal cells of the breast. Macrophages are frequently found in close proximity with myofibroblasts, but it is uncertain whether they are involved in the myofibroblast differentiation during phyllodes tumor progression. Here we show that increased density of tumor-associated macrophage (TAM) correlates with malignant progression of phyllodes tumor. We found that TAMs stimulated myofibroblast differentiation and promoted the proliferation and invasion of phyllodes tumor cells. Furthermore, we found that levels of the chemokine CCL18 in TAM was an independent prognostic factor of phyllodes tumor. Mechanistic investigations showed that CCL18 promoted expression of α-smooth muscle actin, a hallmark of myofibroblast, along with the proliferation and invasion of phyllodes tumor cells, and that CCL18-driven myofibroblast differentiation was mediated by an NF-κB/miR-21/PTEN/AKT signaling axis. In murine xenograft models of human phyllodes tumor, CCL18 accelerated tumor growth, induced myofibroblast differentiation, and promoted metastasis. Taken together, our findings indicated that TAM drives myofibroblast differentiation and malignant progression of phyllodes tumor through a CCL18-driven signaling cascade amenable to antibody disruption. Cancer Res; 77(13); 3605-18. ©2017 AACR.


Subject(s)
Breast Neoplasms/pathology , Macrophages/pathology , Myofibroblasts/pathology , Phyllodes Tumor/pathology , Animals , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Cell Differentiation/immunology , Cell Line, Tumor , Disease Progression , Female , Heterografts , Humans , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Nude , Myofibroblasts/immunology , Myofibroblasts/metabolism , Phyllodes Tumor/immunology , Phyllodes Tumor/metabolism , Signal Transduction
3.
J Cancer Res Ther ; 12(2): 667-70, 2016.
Article in English | MEDLINE | ID: mdl-27461629

ABSTRACT

BACKGROUND: Fibroepithelial lesions of the breast are classified into fibroadenoma and phyllodes tumor (PT). Although WHO has established a well-defined grading system for PT, dilemma of discriminating borderline from malignant PT still exists. Stromal CD10 is a known poor prognostic factor in invasive breast cancer, its expression in fibroepithelial lesions of the breast is not well-documented. Till date, only one study has correlated the CD10 staining score with tumor grade in PT. OBJECTIVE: To evaluate whether the differences in expression patterns of CD10 and staining intensity correlate with the degree of malignancy in fibroepithelial tumors of the breast. MATERIALS AND METHODS: This is a retrospective study in which stromal CD10 expression was studied in 75 cases of fibroepithelial lesions of the breast using immunohistochemistry. Statistical analysis was performed using Chi-square test. RESULTS: There was a statistically significant trend of increasing stromal expression of CD10 with increasing degree of malignancy (P = 0.001). CONCLUSIONS: CD10 staining pattern and its scoring can assist the pathologist to accurately grade the PT of the breast for adequate treatment and can also be used as a target for the development of novel therapies.


Subject(s)
Breast Neoplasms/immunology , Fibroadenoma/immunology , Neprilysin/analysis , Phyllodes Tumor/immunology , Adolescent , Adult , Breast Neoplasms/pathology , Female , Fibroadenoma/pathology , Humans , Middle Aged , Neoplasm Grading , Phyllodes Tumor/pathology , Retrospective Studies , Staining and Labeling
4.
J Clin Pathol ; 58(2): 185-9, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15677540

ABSTRACT

BACKGROUND/AIMS: CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions. METHODS: Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy. RESULTS: There was a progressive increase in the patients' age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours. CONCLUSIONS: CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.


Subject(s)
Breast Neoplasms/immunology , Fibroadenoma/immunology , Neprilysin/immunology , Phyllodes Tumor/immunology , Stromal Cells/immunology , Adolescent , Adult , Aged , Breast Neoplasms/pathology , Female , Fibroadenoma/pathology , Humans , Immunohistochemistry/methods , Middle Aged , Phyllodes Tumor/pathology
5.
J Surg Oncol ; 79(2): 86-92, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11815995

ABSTRACT

BACKGROUND AND OBJECTIVES: Phyllodes tumor (PT) is a biphasic tumor with unpredictable behavior. Our study aimed to evaluate clinicopathologic factors and biomarkers that may be helpful in predicting the outcome of these tumors. METHODS: We evaluated immunoreactivity of p53, c-erbB-2, and Ki-67 in 23 PT treated over a 10-year period. The proliferative activity in PT and expression of p53 and c-erbB-2 were correlated with clinicopathologic features of the tumors and patients' outcome. RESULTS: Positive stromal p53 immunoreactivity was found in PT with atypia, infiltrative borders, high cellularity, as well as in PT that displayed higher then average proliferation index, although none of these parameters reached statistical significance. There was a good correlation between proliferative stromal cell activity expressed Ki-67-labeling index and the malignant features of the tumors. Primary tumors that recurred displayed high proliferative activity. Three of four recurrent tumors showed a progression toward higher malignant phenotype with concomitant increase in proliferative stromal cell activity. c-erbB-2-positive tumors had no particular histologic features or association with either p53 positivity or higher proliferative indices. CONCLUSIONS: p53 expression tends to be more frequent in PT with higher malignant potential but did not predict recurrence. Incompletely excised tumors that recurred displayed high proliferative activity in their primary tumors. Progression toward more malignant phenotype in the recurrent PT was accompanied with increase in stromal cell proliferative activity, suggesting the presence of biological continuity between benign, borderline, and malignant PT.


Subject(s)
Biomarkers, Tumor/immunology , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Ki-67 Antigen/immunology , Phyllodes Tumor/immunology , Phyllodes Tumor/pathology , Receptor, ErbB-2/immunology , Tumor Suppressor Protein p53/immunology , Adolescent , Adult , Aged , Biomarkers, Tumor/analysis , Breast Neoplasms/surgery , Disease Progression , Female , Humans , Immunohistochemistry , Ki-67 Antigen/biosynthesis , Mastectomy , Mastectomy, Segmental , Middle Aged , Phenotype , Phyllodes Tumor/surgery , Prognosis , Prospective Studies , Receptor, ErbB-2/biosynthesis , Survival Analysis , Tumor Suppressor Protein p53/biosynthesis
6.
Zhonghua Bing Li Xue Za Zhi ; 26(6): 337-9, 1997 Dec.
Article in Chinese | MEDLINE | ID: mdl-10374321

ABSTRACT

OBJECTIVE: To investigate the expression of proliferating cell nuclear antigen (PCNA) in breast phylloides cystosarcoma and its clinicopathological signification. METHODS: Immunohistochemistry (SP method) with monoclonal antibodies PC10 against PCNA was performed in 100 cases of phylloides cystosarcoma and 39 cases of adenofibroma. RESULTS: The positive rate of PCNA in phylloides cystosarcoma was 86%. The average PCNA index (PI) of phylloides cystosarcoma was significantly different among every histologic grading (F = 85.33, P < 0.01). The degree of differentiation was lower, the PI was higher. The PI was closely correlated with histologic grading (r's = 0.77). The PI in grade I phylloides cystosarcoma was higher than that in the group of adenofibroma with abundant mesenchymal cells (t = 3.42, P < 0.01). There was only a low correlation between PI and mitotic figures in phylloides cystosarcoma (r = 0.39). CONCLUSIONS: These findings suggest that the detection of PCNA has considerable practical value in reflecting the proliferation of activity of phylloides cystosarcoma, assisting the pathologists to make histologic grading; distinguishing the malignancy from benign ones (differential diagnosis) and evaluating the prognosis.


Subject(s)
Breast Neoplasms/pathology , Phyllodes Tumor/pathology , Proliferating Cell Nuclear Antigen/biosynthesis , Adenofibroma/immunology , Adenofibroma/pathology , Adult , Breast Neoplasms/immunology , Female , Follow-Up Studies , Humans , Middle Aged , Phyllodes Tumor/immunology , Prognosis
7.
Histopathology ; 29(5): 411-9, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8951485

ABSTRACT

Fibroadenomas and mammary phyllodes tumour arise by proliferation of mammary stroma and epithelial elements. However, it is the stromal element that determines the biology of these biphasic tumours. Normal mammary stroma, like most collagenous connective tissue, contains resident populations of CD34+ dendritic interstitial cells and scattered factor XIIIa+ collagen-associated dendrophages. Actin+myofibroblasts are usually absent from mammary stroma in non-disease states. To determine whether CD34+ and factor XIIIa+ cells proliferate in fibroadenomas and phyllodes tumours, and to study myofibroblastic differentiation in these lesions, we examined 19 fibroadenomas in 14 patients along with five low grade and two high grade phyllodes tumours. We employed antibodies against the human progenitor cell antigen CD34, coagulation factor XIIIa and HHF-35 actin. In three fibroadenomas and two phyllodes tumours, we used Ki-67 antigen to study cell proliferation and oestrogen and progesterone receptors to study possible hormonal influence on stromal cells. In all fibroadenomas, CD34 strongly stained interlobular, pericanalicular and intracanalicular fibroblasts with collagenous and/or myxoid features. Four low grade phyllodes tumours also had CD34+ fibroblasts as did one high grade tumour. Actin reactivity varied and was most pronounced in six fibroadenomas resembling the so-called cellular variant, while seven regular fibroadenomas had no actin+stromal cells and six had only focal and weak actin+stromal cells. Factor XIIIa+ cells were prominently admixed in the stroma of all tumours studied comprising from 5% to 20% in fibroadenomas and, focally, up to 50% in phyllodes tumours. Oestrogen and progesterone receptors were expressed only in glandular elements. Ki-67 index in stromal cells was 1% to 3% in fibroadenoma, 10% to 20% in low grade, and 20% to 40% in high grade phyllodes tumour. We conclude that fibroadenomas and some phyllodes tumours are composed of CD34+ fibroblasts that show varying myxoid, collagenous or myofibroblastic differentiation. The fibroblasts are accompanied by a subset of dendritic histiocytes that express factor XIIIa. Fibroadenoma variants show prominent collagenous actin+myofibroblastic differentiation of CD34+ stromal cells, sometimes with a gradient of CD34 down-regulation. Fine-needle or limited stereotactic core biopsy of these biphasic tumours, if they yield only stromal cells, must be distinguished from other CD34+ stromal tumours. Increased factor XIIIa+ dendrophage populations were seen in phyllodes tumours, especially in two high grade tumours that had malignant fibrous histiocytoma-like features, suggesting clonal evolution toward the fibrohistiocytic final pathway. Further study of CD34 and factor XIIIa+ mammary stromal cells in larger numbers of phyllodes tumours might ascertain whether increasing factor XIIIa reactivity correlates with differentiation and increased tumour aggressiveness.


Subject(s)
Antigens, CD34/metabolism , Breast Neoplasms/pathology , Fibroadenoma/pathology , Phyllodes Tumor/pathology , Transglutaminases/metabolism , Adult , Biomarkers/analysis , Breast Neoplasms/immunology , Breast Neoplasms/metabolism , Cell Differentiation , Dendritic Cells/metabolism , Fibroadenoma/immunology , Fibroadenoma/metabolism , Fibroblasts/metabolism , Humans , Immunohistochemistry , Immunophenotyping , Middle Aged , Phyllodes Tumor/immunology , Phyllodes Tumor/metabolism
8.
Breast Cancer Res Treat ; 17(2): 131-8, 1990 Dec.
Article in English | MEDLINE | ID: mdl-1965788

ABSTRACT

Malignant cystosarcoma phylloides (CP) is a relatively rare cancer of the breast. A CP tumor was processed as part of a tumor acquisition, propagation, and preservation program in patient biotherapy. Two tissue culture cell lines were developed from this tumor, one directly from the biopsy, another from a xenograft tumor grown in athymic mice. The two cell lines were similar in character. There was strong immunochemical reactivity with antibodies to vimentin, type I collagen, and type III collagen. There was no reactivity with antibodies to cytokeratin and epithelial membrane antigen. Both cell lines were aneuploid, clonogenic in soft agar, and tumorigenic in nude mice. 5 alpha-dihydrotestosterone and thyroxine added to the culture medium stimulated growth, while testosterone, 17 beta-estradiol, and 4-hydroxytamoxifen were without effect. Dexamethasone and cortisol were inhibitory at high doses (10(-6) M). Dibutyryl cyclic AMP, theophylline, and vitamin C were all inhibitory. The biopsy contained tumor-infiltrating lymphocytes which proliferated in cultures containing interleukin 2. The expanded lymphocytes were activated T cells which had the capacity to lyse tumor cells. These results suggest possibilities in the therapy of cystosarcoma phylloides involving vitamin C, certain hormones, and tumor-infiltrating lymphocytes.


Subject(s)
Breast Neoplasms/therapy , Phyllodes Tumor/therapy , Tumor Cells, Cultured , Adult , Animals , Female , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Phyllodes Tumor/immunology , T-Lymphocytes, Cytotoxic/immunology , Transplantation, Heterologous
9.
Pathol Res Pract ; 186(4): 427-38, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2174150

ABSTRACT

Using serial frozen sections, monoclonal antibodies and an indirect immunoperoxidase method, 13 fibroadenomas (FA) and 3 cystosarcomas phyllodes (CSP) were analyzed for the expression of Egp34, HEA319-antigen, leucocyte differentiation antigens CD10, CD30, CD57, CD72, CDw75, and CD77, epidermal growth factor receptor (EGFR), estrogen (ER) and progesterone receptor (PR), and transferrin receptor (CD71). Egp34, CDw75, HEA319 antigen, CD10, and CD30 turned out to be consistently expressed in different cell types constituting FA and CSP and revealed that in malignant CSP the myoepithelial compartment acquires the ability to invade the stroma. Phenomenologically, the variable mode of expression of CD57 in myoepithelial cells, of CD77 in ductal epithelium, and of CD72 in both epithelial and stromal cells is suggestive for reflecting differences in their functional state but cannot be further interpreted at present. Expression of PR and ER was restricted to duct cells and was relatively independent, non-systematical. However, expression of ER and EGFR was inverse. This was also true for EGFR and CD71 in both duct cells and myoepithelial cells of FA. In contrast, stromal cells of FA were able to co-express EGFR and CD71 in the absence of PR and ER. This suggests a hormone-independent stimulation of the stromal cell compartment, possibly leading to local proliferation as the primary event in tumorigenesis of FA. In malignant CSP, however, the main proliferating cell is an abnormally mobile, HEA319 antigen-, CD10- and CD30-positive myoepithelial cell found to co-express ERFR and CD71 which is abnormal for this cell type but encountered in (myo-)fibroblasts of FA.


Subject(s)
Adenofibroma/immunology , Antigens, Neoplasm/analysis , Breast Neoplasms/immunology , Phyllodes Tumor/immunology , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Antibodies, Monoclonal , Antigens, CD/analysis , Antigens, Surface/analysis , ErbB Receptors/analysis , Female , Humans , Immunoenzyme Techniques
10.
Cancer ; 57(5): 1042-5, 1986 Mar 01.
Article in English | MEDLINE | ID: mdl-3002592

ABSTRACT

Tissue carcinoembryonic antigen (CEA) and cytosolic estrogen and progesterone receptors were studied in 15 patients with cystosarcoma phyllodes (CSP) aiming at predicting recurrence of the tumor. Polyclonal (rabbit, monospecific) and monoclonal (mouse) antibodies anti-CEA were applied to formalin-fixed, paraffin-embedded tissue sections using an indirect (PAP) immunoperoxidase method. Estrogen receptors (ER) and progesterone (PR) receptors were determined by a charcoal-dextran method. ER was detected in 4 of 15 primary CSP (mean level, 22 fmol/mg protein). CEA was demonstrated exclusively in the epithelial components of 12 of 15 tumors. Strong expression of CEA was verified in eight tumors, six of which recurred locally one or more times. None of the seven tumors negative or weakly reactive for CEA had recurrences. No correlation was found between expression of tissue CEA and steroid receptor status of the tumors. Our data indicate that strong CEA expression in CSP correlates with tumor recurrence.


Subject(s)
Breast Neoplasms/immunology , Carcinoembryonic Antigen/analysis , Neoplasm Recurrence, Local/immunology , Phyllodes Tumor/immunology , Adult , Breast Neoplasms/metabolism , Breast Neoplasms/surgery , Epithelium/immunology , Female , Follow-Up Studies , Histocytochemistry , Humans , Immunoenzyme Techniques , Middle Aged , Neoplasm Recurrence, Local/metabolism , Phyllodes Tumor/metabolism , Phyllodes Tumor/surgery , Prognosis , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis
13.
J Histochem Cytochem ; 26(7): 532-41, 1978 Jul.
Article in English | MEDLINE | ID: mdl-80418

ABSTRACT

An indirect immunoperoxidase method was first used to localize mouse mammary tumor virus (MMTV) antigens in paraffin sections of mammary tumors of Paris RIII and CD8F1 mice. By using the same method, an antigen with cross-reactivity to a group-specific antigen (gp52, a 52,000 dalton glycoprotein) of MMTV was detected in paraffin sections of human breast carcinomas. The specificity of this reaction with antibody against MMTV was examined by absorption of the IgG with: a) purified gp52; b) several relevant and irrelevant viral preparations; c) normal human plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid; d) sheep erythrocytes, bovine mucin and fetal calf serum. Only MMTV and prufied gp52 eliminated the immunohistochemical reaction in human breast tumors. Positive reactions were seen in 73 of 191 (38%) breast carcinomas of various histopathologic types, while negative reactions were obtained in all 137 normal and benign cases tested. A positive reaction of uncertain specificity was observed in foci of apocrine metaplasia. With one exception, 99 carcinomas from 13 organs other than breast and eight cystosarcomas were negative.


Subject(s)
Antigens, Viral , Breast Neoplasms/immunology , Cross Reactions , Mammary Neoplasms, Experimental/immunology , Adenocarcinoma/immunology , Animals , Apocrine Glands/pathology , Epitopes , Humans , Immunoenzyme Techniques , Metaplasia/immunology , Mice , Phyllodes Tumor/immunology
SELECTION OF CITATIONS
SEARCH DETAIL
...