bromochloroacetic-acid and Fibrocystic-Breast-Disease

Topics: Breast; Breast Neoplasms; Cells, Cultured; Cytoskeleton; Epithelium; Fibrocystic Breast Disease; Gene Expression Regulation, Neoplastic; Humans; Intermediate Filament Proteins; Keratins; Neoplasm Proteins; Organoids; Phosphorylation; Protein Processing, Post-Translational; Tumor Cells, Cultured

Topics: Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Diagnosis, Differential; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins; Neoplasm Proteins; Neoplasm Recurrence, Local; S100 Proteins; Triple Negative Breast Neoplasms

Proliferative epithelial breast lesions include a wide variety of benign hyperplastic and noninvasive neoplastic lesions, as well as invasive carcinomas. Mammographically these lesions may show microcalcifications, architectural distortions or mass lesions. The task of the pathologist begins with a preoperative diagnosis by means of minimally invasive biopsy. His diagnosis forms the basis for not only the radiological-pathological correlation diagnosis, but also for the management of benign proliferative breast disease lesions, as well as therapeutic decisions in the case of malignant lesions.In daily practice, immunohistochemistry is the method of choice for clarifying difficult cases. The aim of this chapter is to describe the relevant markers in breast pathology and to provide an algorithmic approach to different proliferative breast disease lesions.

Topics: Biomarkers; Biopsy; Breast Diseases; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Diagnosis, Differential; Epithelium; Female; Fibrocystic Breast Disease; Humans; Hyperplasia; Immunohistochemistry; Keratins

Microglandular adenosis (MGA) of the breast is widely known as a benign lesion that can mimic invasive carcinoma. In situ and invasive carcinomas have been described as arising in MGA, but which cases of MGA will progress to carcinoma is unclear. Criteria for distinguishing uncomplicated MGA, MGA with atypia (AMGA), and carcinoma arising in MGA (MGACA) are not standardized. The primary objective of this study was to illustrate the clinical, histopathologic, and immunophenotypical characteristics of MGA, AMGA, and MGACA in an effort to provide criteria for distinguishing the 3 types. We retrospectively identified 108 cases seen at M.D. Anderson Cancer Center between 1983 and 2007 that had a diagnosis of MGA. Of the 108 cases, 65 cases had available material for review. Inclusion criteria were glands of MGA expressing S-100 protein and lacking myoepithelial layer (smooth muscle actin negative). Eleven out of 65 cases qualified to have an MGA component; myoepithelial layer was detected in the remaining 54 cases and were classified as adenosis. Out of the 11 MGA patients, there were 3 patients with uncomplicated MGA, 2 had AMGA, and 6 had MGACA. Staining indices for the cell cycle markers p53 and Ki-67 were used to compare the 3 tumor categories. Additional staining for other tumor markers [estrogen and progesterone receptors, HER2, epidermal growth factor receptor (EGFR), c-kit, CK5/6, and CK18] were performed. Patient demographics, tumor radiologic features, and clinical follow-up data were collected for all cases. Multiple invasive histologic components were identified in each of the MGACA cases. All invasive MGACAs had a duct-forming component. In addition, basal-like component was present in 2 cases, aciniclike in 2, matrix producing in 4, sarcomatoid in 1, and adenoid cystic in 1. All tumors had strong and diffuse CK8/18 and EGFR expression but no estrogen receptor, progesterone receptor, HER2 (ie, triple negative), or CK5/6 expression. C-kit was focally expressed in 2 of the MGACAs. Ki-67 and p53 labeling indices was < 3% in all MGAs, 5% to 10% in the AMGAs, and > 30% in MGACAs. In a follow-up ranging from 14 days to 8 years, none of the MGA cases recurred. One of the AMGA cases recurred as invasive carcinoma in a background of AMGA after 8 years following incomplete excision of the lesion. Three out of 6 MGACA cases (50%) required multiple consecutive resections ending up with mastectomy due to involved margins by invasive or in situ carcinoma. Two ou

Topics: Actins; Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Cell Transformation, Neoplastic; Diagnosis, Differential; Diagnostic Errors; Disease Progression; ErbB Receptors; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mastectomy; Middle Aged; Neoplasm Invasiveness; Precancerous Conditions; Proto-Oncogene Proteins c-kit; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; S100 Proteins; Texas; Time Factors; Treatment Outcome; Tumor Suppressor Protein p53

Nerve growth factor receptor (NGFR) is a transmembrane glycoprotein without intrinsic tyrosine kinase activity, whose expression is not restricted to neural cells. NGFR is reported to act as a tumour suppressor, negatively regulating cell growth and proliferation. NGFR expression was immunohistochemically analysed in normal breast tissue and in 140 benign, biphasic and preinvasive breast lesions, in 22 tumours with myoepithelial differentiation and in two cohorts of breast cancer patients: a series of 245 invasive breast carcinomas studied with tissue microarrays and 37 high-grade invasive ductal carcinomas with basal-like immunophenotype. NGFR consistently displayed membrane reactivity in myoepithelial cells arranged as a continuous layer around normal ducts and lobular units, intralobular fibroblasts, vascular adventitia and nerve bundles. Myoepithelial cells of benign proliferations and pre-invasive lesions were consistently positive for NGFR. Scattered NGFR-positive cells were observed in solid areas of six out of nine cases of hyperplasia of usual type, whereas in flat atypia, lobular carcinoma in situ and virtually all cases of ductal carcinoma in situ (97.5%), NGFR was restricted to the myoepithelial layer. Positivity for NGFR was observed in 11 out of 245 (4.5%) breast carcinomas, nine out of 20 (45%) metaplastic breast carcinomas and 14 out of 37 (38%) basal-like breast carcinomas. NGFR expression in invasive tumours significantly correlated with that of cytokeratins 5/6 (P<0.05), 14 (P<0.0001) and 17 (P<0.0005) and EGFR (P<0.0001) and displayed an inverse correlation with oestrogen and progesterone receptors (both, P<0.0001). NGFR showed a statistically significant association with longer disease-free (P<0.05) and overall survival (P<0.01) in the cohort of patients with basal-like carcinomas. This study demonstrates the usefulness of NGFR as a new adjunct marker to identify myoepithelial cells in preinvasive lesions and myoepithelial differentiation in breast carcinomas. Furthermore, provisional data in a small number of basal-like breast carcinomas suggest that NGFR may identify a subgroup of basal-like breast carcinomas with good prognosis.

Topics: Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Epithelial Cells; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratin-14; Keratin-5; Keratin-6; Keratins; Myoepithelioma; Neoplasm Invasiveness; Nerve Tissue Proteins; Receptors, Estrogen; Receptors, Growth Factor; Receptors, Nerve Growth Factor; Receptors, Progesterone; Survival Analysis

According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (n=14), papilloma (n=22), tubular adenoma (n=3), and adenosis (n=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5/6-expressing basal-type cells within the proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS.

Topics: Adenoma; Breast Diseases; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Chromosome Aberrations; Female; Fibrocystic Breast Disease; Humans; Hyperplasia; In Situ Hybridization, Fluorescence; Keratins; Molecular Weight; Nucleic Acid Hybridization; Papilloma, Intraductal; Precancerous Conditions

Histopathological identification of invasive breast carcinoma in its earliest phases is fraught with pitfalls. Preinvasive malignant lesions complicated by radial scar, sclerosing adenosis, and lobular cancerization, among other lesions, may simulate invasive carcinoma. Fibrosis, inflammatory reaction, and other stromal changes around in situ carcinoma may mask microinvasive foci on routine stains. Conventional immunohistochemistry to demonstrate basement membrane or myoepithelial cell layer may not, by itself, be unequivocally diagnostic of invasion. We performed a novel double immunoenzyme labeling technique using an avidin-biotin complex peroxidase-diaminobenzidine system for smooth-muscle actin followed by an alkaline phosphatase anti-alkaline phosphatase-new fuchsin system for cytokeratin antigen on formalin-fixed, paraffin-embedded histology sections to evaluate 32 such problematic cases. The initial histologic impression with hematoxylin and eosin staining alone was as follows-first group: microinvasive carcinoma-10; second group: carcinoma in situ--"stromal invasion cannot be ruled out"--15; third group: frankly infiltrating carcinoma of various grades and morphologic types-6. The last group served as positive control for invasion. One fibroadenoma with fine-needle-aspiration-induced artifact simulating stromal invasion was also included. The double immunoenzyme labeling technique imparted a dark brown color to the myoepithelial cells and a vivid red color to the epithelial cells, making individual or loosely cohesive groups of malignant epithelial cells infiltrating the stroma easily detectable, whereas their in situ counterparts were contained within dark brown myoepithelial boundaries. The TNM 1997 definition of pT1mic, i.e., extension of malignant cells in the stroma with no focus measuring >0.1 cm, was followed to classify microinvasion. In the first group, microinvasion was confirmed in six cases but was not demonstrable in four. In the second group, definite invasion was identified in five cases, ruled out in nine, and in one case the suspicion of early invasion could not be entirely ruled out even after double immunoenzyme labeling. Thus, it was possible to render a definite opinion regarding presence or absence of invasion in 24 of 25 (96%) cases diagnosed as or suspected to be microinvasive. The precise and simultaneous elucidation of topography between malignant cells and myoepithelial cells on a single permanent section makes this tech

Topics: Actins; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Invasiveness; Sclerosis

To carry out a comprehensive study of cytokeratin expression in benign and malignant breast epithelium and breast myoepithelial cells; to examine changes in the cytokeratin profile in malignant and benign epithelium and in carcinomas of increasing histological grade.. Frozen sections from fibroadenomas (19 cases), fibrocystic disease (19 cases), and infiltrating ductal (68 cases), lobular (seven cases), and mucinous carcinomas (three cases) were examined using a panel of monoclonal antibodies.. The luminal epithelium in all fibroadenomas and all cases of fibrocystic disease, as well as tumour cells in most carcinomas, reacted with the specific antibodies to cytokeratins 7, 8, 18, and 19 and to antibodies which included these cytokeratins in their specificities (Cam 5.2, AE1, AE3, RCK102, and LP34). In a few ductal carcinomas none of the tumour cells reacted for cytokeratins 7, 8, or 18. Three ductal carcinomas expressed cytokeratin 14. Only occasional cases expressed cytokeratins 3, 4, 10, and 13. Antibodies which included cytokeratins 5 and 14 in their specificities detected myoepithelial cells less efficiently than antiactin antibodies.. The cytokeratin profiles in the luminal epithelium in benign breast disease and in tumour cells in most carcinomas are similar in most cases. Some carcinomas, however, are negative for cytokeratins 7, 8, or 18. This may provide a means of predicting the biological behaviour of a histologically borderline lesion.

Topics: Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Epithelium; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Proteins

Topics: Biopsy, Needle; Breast Neoplasms; Diagnosis, Differential; Female; Fibrocystic Breast Disease; Humans; Keratins; Middle Aged; Phyllodes Tumor

Breast carcinoma arose in or in conjunction with microglandular adenosis (MGA) in 14 of 60 (23%) patients with MGA listed in the authors' files. This article describes the clinicopathologic and immunohistochemical features and prognosis of these carcinomas. The median patient age was 47 years (range, 26-68 years). All patients had a mass. Six (43%) had a family history of breast carcinoma. Lymph node metastases were found in 3 of 11 axillary dissections. Ten patients treated by mastectomy were recurrence-free, with a median follow-up of 57 months (range, 3-108 months). Two of three patients treated by excisional surgery were recurrence-free 12 and 105 months later. The third woman had bone metastases at 51 months and was alive 98 months after treatment. Carcinoma arose in the MGA in 13 patients. In these patients, in situ carcinoma was found in expanded MGA glands composed of cells with vesicular poorly differentiated nuclei. One patient with benign MGA had carcinoma develop in the opposite breast that was not associated with MGA. When it arose in MGA, basement membranes were present in benign MGA and in situ carcinoma but tended to be disrupted in invasive foci that appeared to be formed by coalescent MGA glands. Strong immunoreactivity for cytokeratin, S-100, and cathepsin D was detected in carcinomas. Two carcinomas had nuclear progesterone receptors, and one of these had estrogen receptors. One carcinoma had positive findings for HER-2neu, and four had immunoreactivity for p53 protein. The following conclusions were drawn from these observations: (1) carcinomas arising in MGA have a distinctive histopathologic pattern; (2) the carcinomas are composed of epithelial cells (cytokeratin positive, actin negative) that are strongly immunoreactive for S-100 protein and cathepsin D; and (3) with a median follow-up of nearly 5 years, patients with these carcinomas had a relatively favorable prognosis, despite histopathologic and immunohistochemical features usually associated with a poor prognosis.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Combined Modality Therapy; Family; Female; Fibrocystic Breast Disease; Follow-Up Studies; Humans; Keratins; Lymphatic Metastasis; Middle Aged; Treatment Outcome

Mammary ductal foam cells are present in normal breast tissue as well as in a number of breast diseases. Such foam cells tend to be in particular abundance with fibrocystic changes of the breast. Foam cells may appear within duct lumens or plastered in cohesive masses along duct walls, simulating an epithelial structure. The nature and origin of these innocuous-appearing cells, based on morphologic studies, remain a controversy, for they appear to be of epithelial derivation. This study was undertaken to determine the nature of intraductal "foam" cells and their origin in the breast. Nine cases of adult fibrocystic disease were examined immunohistochemically with antibodies to cytokeratins (Mak-6, Cam 5.2), leukocyte common antigen, and the following macrophage antibodies: KP-1 (CD68), HAM 56, and MAC 387. The lysozyme and alpha-1-antitrypsin content of foam cells also was studied. The immunohistochemical data in this study confirm the macrophage character of these foam cells, which are positive for CD68, HAM 56, and MAC 387, lysozyme, and alpha-1-antitrypsin and negative for leukocyte-common antigen and cytokeratins.

Topics: Antibodies; Breast; Cell Line; Female; Fibrocystic Breast Disease; Foam Cells; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Leukocyte Common Antigens; Macrophages; Reference Values; Staining and Labeling

Topics: Actins; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Cell Division; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins

To determine vimentin expression in epithelial cells in benign breast disease and malignant breast tumours; to assess the value of vimentin expression as a prognostic indicator in breast carcinoma.. Frozen and formalin fixed, paraffin wax embedded sections from 78 carcinomas, three phyllodes tumours, 19 fibroadenomas and 19 cases of fibrocystic disease were examined with a monoclonal antibody from the V9 clone. A correlation between vimentin expression and known prognostic indicators was sought in ductal carcinomas. The intracellular localisation of vimentin was examined in benign and malignant lesions.. Vimentin expression was identified on frozen section in the cells of ductal (53%), lobular (86%), and mucinous (33%) carcinomas and in the luminal epithelium of fibroadenomas (68%), cases of fibrocystic disease (47%), and a malignant phyllodes tumour. Formalin fixation reduced the percentage of carcinomas and cases of benign disease in which vimentin was detected. This reduction was more pronounced in fibroadenoma and fibrocystic disease than in ductal carcinoma. Associations were identified between vimentin expression as detected on frozen section and tumour grade, size, number of lymph nodes affected, oestrogen receptor content and growth fraction. Only the association with grade was significant (p = 0.045). There was no significant correlation between any of these prognostic variables and vimentin expression on paraffin wax sections. There was no difference in the intracellular localisation of vimentin staining between benign and malignant lesions, or between low and high grade ductal carcinomas.. There is some loss of vimentin immunoreactivity after formalin fixation. Vimentin expression does not assist in differentiating between benign and malignant breast disease, but is correlated with tumour grade in ductal carcinoma.

Topics: Adenofibroma; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Epithelium; Female; Fibrocystic Breast Disease; Formaldehyde; Frozen Sections; Humans; Immunoenzyme Techniques; Keratins; Paraffin Embedding; Phyllodes Tumor; Prognosis; Vimentin

This study on the different types of epithelial hyperplasia in fibrocystic disease was inspired by the observation of myoepithelial (basocellular) hyperplasia identified by strong expression of S100 protein and a weak reaction with antibodies against cytokeratin (KL1) in cells forming solid and acinar buds. The cells do not contain immunohistochemically detectable actin or desmin. Glandular transformation and proliferation give rise to basocellular circumductal adenosis. Normal breast tissue, 51 cases of fibrocystic disease with mild, florid and atypical hyperplasias, 7 fibroadenomas and 20 cases of carcinoma in situ were studied and a semiquantitative analysis revealed basal buds and adenosis in less than 40% of cases of mild hyperplasia and up to 73% in florid hyperplasia. Epitheliosis is characterized by a heterogeneous cell pattern with cells positive for S100 protein in 30-60%, but in small ducts up to 100% with an immediate connection to the basal cell layer were positive. Carcinoma in situ contained very rare tumour cells positive for S100 protein. The cells expressing S100 protein in terminal ducts, in adenosis and epitheliosis showed only some of the characteristics of myoepithelial cells, since they lack immunoreactivity with antibodies against actin. These basal clear cells are interpreted as transitional or indeterminate cells with features of myoepithelial precursor cells, but with the ability to develop basocellular nodular and glandular hyperplasia in the ductulo-lobular units in cases of adenosis and juvenile fibroadenoma.

Topics: Adenofibroma; Breast; Breast Diseases; Breast Neoplasms; Cell Division; Female; Fibrocystic Breast Disease; Humans; Hyperplasia; Immunohistochemistry; Keratins; Myoepithelioma; S100 Proteins

Microglandular adenosis (MA) of the breast is a benign, disorganized proliferation of glands lined by a single layer of cells. As such, differential diagnosis between MA and tubular carcinoma may be challenging in selected cases. A panel of antibodies was applied to 10 cases of MA and 10 of tubular carcinoma to investigate the potential benefit of immunohistochemistry in the separation of these lesions and the possible role of myoepithelial cells in MA. The luminal cells in nine cases of MA were surrounded by a cuff of muscle-specific actin-reactive cells, which also coexpressed cytokeratin and vimentin. The immunophenotype of these cells is characteristic of myoepithelial differentiation, which was heretofore thought to be lacking in MA. This finding demonstrates that myoepithelial cells are indeed present in MA subjacent to luminal epithelial cells; moreover, it distinghuishes MA from tubular carcinoma, all examples of which were actin negative in this analysis. In addition, circumferential type IV collagen deposition was observed around constituent glands of MA in nine cases but was lacking in all tubular carcinomas. Other markers included in this evaluation (S100 protein, gross cystic disease fluid protein 15, carcinoembryonic antigen, estrogen receptor protein) were of no differential diagnostic value.

Topics: Actins; Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Collagen; Female; Fibrocystic Breast Disease; Humans; Immunoenzyme Techniques; Immunophenotyping; Keratins; Middle Aged; S100 Proteins; Vimentin

The authors studied by immunohistochemistry the intermediate filament (IF) protein profile of 66 frozen samples of breast tissue, including normal parenchyma, all variants of fibrocystic disease (FCD), fibroadenomas, cystosarcoma phylloides, and ductal and lobular carcinomas. Monoclonal antibodies (MAbs) to cytokeratins included MAb KA 1, which binds to polypeptide 5 in a complex with polypeptide 14 and recognizes preferentially myoepithelial cells; MAb KA4, which binds to polypeptides 14, 15, 16 and 19; individual MAbs to polypeptides 7, 13, and 16, 17, 18, and 19, and the MAb mixture AE1/AE3. The authors also applied three MAbs to vimentin (Vim), and three MAbs to glial filament protein (GFP). Selected samples were studied by double-label immunofluorescence microscopy and by staining sequential sections with some of the said MAbs, an MAb to alpha-smooth muscle actin, and well-characterized polyclonal antibodies for the possible coexpression of diverse types of cytoskeletal proteins. Gel electrophoresis and immunoblot analysis also were performed. All samples reacted for cytokeratins with MAbs AE1/AE3, although the reaction did not involve all cells. Monoclonal antibody KA4 stained preferentially the luminal-secretory cells in the normal breast and in FCD, whereas it stained the vast majority of cells in all carcinomas. Monoclonal antibody KA1 stained preferentially the basal-myoepithelial cells of the normal breast and FCD while staining tumor cell subpopulations in 4 of 31 carcinomas. Vimentin-positive cells were found in 8 of 12 normal breasts and in 12 of 20 FCD; in most cases, Vim-reactive cells appeared to be myoepithelial, but occasional luminal cells were also stained. Variable subpopulations of Vim-positive cells were noted in 9 of 20 ductal and in 1 of 7 lobular carcinomas. Glial filament protein-reactive cells were found in normal breast lobules and ducts and in 15 of 20 cases of FCD; with rare exceptions, GFP-reactivity was restricted to basally located, myoepithelial-appearing cells. Occasional GFP-reactive cells were found in 3 of 31 carcinomas. Evaluation of sequential sections and double-label immunofluorescence microscopy showed the coexpression of certain cytokeratins (possibly including polypeptides 14 and 17) with vimentin and alpha-smooth muscle actin together with GFP in some myoepithelial cells. The presence of GFP in myoepithelial cells was confirmed by gel electrophoresis and immunoblotting. Our results indicate that coexpression

Topics: Adenofibroma; Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Female; Fibrocystic Breast Disease; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Phyllodes Tumor; Reference Values; Vimentin

The immunohistochemical reactivity on frozen sections of diverse benign and malignant epithelial proliferations of human breast tissue from 156 patients was examined using antibodies to different cytokeratins. Antibodies recognizing cytokeratins 18 and 19 reacted with luminal epithelial cells but not with myoepithelial cells of normal mammary gland, cystic disease, adenosis, papilloma, and fibroadenoma or with a subpopulation of proliferating cells in sclerosing adenosis and epitheliosis. These antibodies reacted with the tumor cells of all in situ and invasive carcinomas. KA1 antibody, which by one- and two-dimensional gel electrophoresis and immunoblotting was shown to bind preferentially to cytokeratin 14 in a complex with cytokeratin 5, reacted with the nonproliferating myoepithelium of normal gland, cystic disease, adenosis, papilloma, fibroadenoma, and in situ carcinoma; it also reacted with a subpopulation of proliferating cells in sclerosing adenosis and epitheliosis (papillomatosis) but was negative with the tumor cells of all preinvasive and most invasive carcinomas. In adenotic and epitheliotic proliferations, groups of cells were identified that reacted strongly with KA1 antibody in addition to antibodies to cytokeratins 18 and 19. The data are discussed with respect to epithelial cell heterogeneity in the breast. We show that by using such antibodies, benign epithelial proliferations are clearly distinguished from carcinomas.

Topics: Adenofibroma; Adult; Aged; Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Diagnosis, Differential; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins; Middle Aged; Papilloma

The distribution of keratins 8 and 17 and of vimentin in 28 normal human mammary tissue samples, 16 benign tumors, 26 fibrocytic diseases and 52 malignant breast tumors have been studied using monoclonal antibodies HI, E3 and NT30, respectively. Three cell populations in normal mammary epithelium have been identified: luminal epithelium containing keratin 8, myoepithelium of the lobular structures positive for vimentin, and myoepithelium of extralobular ducts positive for keratin 17. In different kinds of benign tumor and dysplastic proliferation a mosaic of cells with all normal phenotypes has been observed. The majority of cells co-expressed keratins 8 and 17 or vimentin. In the overwhelming majority of carcinomas, cells did not contain myoepithelial markers (keratin 17 and vimentin) but expressed only keratin 8 specific to normal luminal epithelium.

Topics: Antibodies, Monoclonal; Biopsy; Breast; Breast Neoplasms; Epithelium; Female; Fibrocystic Breast Disease; Fluorescent Antibody Technique; Humans; Keratins; Vimentin

This report describes the immunocytochemical localization of a human basal- or myoepithelial-specific anti-keratin antibody in benign and malignant breast disease. Reactivity patterns with this antibody have demonstrated the lack of myoepithelial or basal epithelial participation in most benign breast specimens examined including those displaying cystic disease, fibrosis, or hyperplasia. However, in specimens of sclerosing adenosis, strong reactivity with the majority of cells in most ducts suggests a major participation of the myoepithelial cell type. Analysis of 118 breast carcinoma specimens has demonstrated strong, homogeneous reactivity in 4% of the specimens, suggesting a role for the basal epithelial cell in malignancy of the human mammary gland and implications for the prognosis of such tumors. Antigenic characterization of the malignant and benign mammary specimens which are uniformly reactive with the antibody has demonstrated the presence of a 51 kd keratin polypeptide not found in the non-reactive specimens.

Topics: Biomarkers, Tumor; Breast Diseases; Breast Neoplasms; Cross Reactions; Epithelium; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1

Antibodies to different intermediate filament proteins can be used to distinguish cells of epithelial, mesenchymal, muscle, glial and neuronal origin. Antibodies to prekeratin which characterize cells of epithelial origin, and antibodies to vimentin which recognize cells of mesenchymal origin have been used to study twenty cases of breast carcinoma (sixteen infiltrating ductal carcinomas and four infiltrating intraductal carcinomas), two cases of cystic breast disease, two fibroadenomas and one case of benign cystosarcoma phylloides. The prekeratin and vimentin were detected using specific antibodies to these proteins by immunofluorescence microscopy using alcohol fixed paraffin-embedded tissues. In eighteen out of the twenty carcinomas the tumor cells were strongly and specifically stained by antibodies to prekeratin. DIfferent tumors gave different patterns of prekeratin staining. In contrast, when the same specimens were tested with the vimentin antibody, the tumor cells were unstained, and instead only the usual strong staining to fibroblasts and blood vessels in the stroma was observed. In cystic breast disease, fibroadenomas, and benign cystosarcoma phylloides, cells of epithelial origin were strongly stained by the prekeratin but not by the vimentin antibody.

Topics: Adenofibroma; Breast Neoplasms; Cytoskeleton; Female; Fibrocystic Breast Disease; Fluorescent Antibody Technique; Humans; Keratins; Microscopy, Electron; Phyllodes Tumor