Epithelial Membrane Antigen Positivity Research Articles

Paraffin section immunohistochemistry in the diagnosis of Hodgkin's disease and anaplastic large cell (CD30+) lymphomas

Morphological and immunohistological studies were carried out on a series of 137 lymphomas including CD30+ anaplastic large cell (ALC) lymphomas (48 cases) and non-lymphocyte predominant Hodgkin's disease (HD) (89 cases), with the aim of assessing in situ expression of a combination of antibodies including anti-CD30/BerH2, epithelial membrane antigen (EMA), CD15 and CD45, in addition to other monoclonal antibodies suitable for paraffin tissues. A greater proportion of cases of ALC lymphomas than of HD exhibited positivity for CD45 (91.7% vs 17.6%), EMA (56.2% vs 4.5%), CD43 (53.6% vs 13.1%) and CD45RO (39.5% vs 3.5%), whereas Reed-Sternberg (RS) cells in HD most frequently expressed CD15 (93.2% vs 20.8%) antigen. Moreover, in 35 of 48 (72.9%) ALC lymphomas tumour cells expressed the CD30+, CD45+, CD15-, EMA- or + phenotypic profile, while in the same percentage (62/85) of HD cases RS cells were found to express the CD30+, CD45-, CD15+, EMA- profile. This study suggests that the differential expression of CD45, EMA, and CD15 may be used in the separation of ALC lymphomas and HD. However, co-expression of CD30, CD45 and CD15 antigens by RS cells in HD (14/85 cases, 16.5% in this series) and by tumour cells in ALC lymphomas (9/48 cases, 18.7% in this series) may be encountered in a non-negligible fraction of cases.

An immunohistochemical study of epithelial membrane antigen, cytokeratin, and vimentin in papillary thyroid carcinoma. Recognition of lethal and favorable prognostic types.

Immunoreactivity for epithelial membrane antigen (EMA), cytokeratin, and vimentin was investigated in 15 papillary thyroid carcinomas (PTC) with distant metastases, 25 PTC without distant metastases, and 34 occult PTC without distant metastases that were found incidentally at autopsy. More than 50% of the tumor cells were positive for EMA in 7 (47%) of 15 PTC with distant metastases, 0 (0%) of 25 PTC without distant metastases, and 1 (3%) of 34 occult PTC. The incidence of EMA positivity in PTC with distant metastases was significantly different from that of both PTC without distant metastases and occult PTC (P < 0.001). Cytokeratin reactivity was similar in the three groups, and almost all PTC stained strongly for cytokeratin. Concerning vimentin positivity, there were no significant differences in three groups; however, PTC with distant metastases tended to stain more weakly or focally than PTC without distant metastases or occult PTC. These results suggest that EMA reactivity may be a useful factor for anticipating the individual risk of distant metastasis or death from PTC at the time of initial surgical treatment.

The distribution of epithelial membrane antigen in thymic epithelial neoplasms.

Thymic carcinomas arising within a thymoma have been reported, but the relationship between thymoma and thymic carcinoma is poorly understood. Epithelial membrane antigen (EMA) is known to be an effective marker for establishing the epithelial nature of neoplastic cells, and it is reported that staining of tumors is clearly related to the degree of tumor differentiation. Eighty-one thymomas (59 noninvasive, 22 invasive) and 14 thymic carcinomas were studied immunohistologically using antiepithelial membrane antigen (anti-EMA) monoclonal antibody. Thymic carcinomas tended to express much larger quantities of EMA than thymomas, and instances of EMA-positive thymoma were seen significantly more often in invasive thymomas than in noninvasive ones (P < 0.05). However, EMA positivity was also associated with gland-like structures, which were not necessarily associated with malignant disease. Nevertheless, in view of the concept that thymoma and thymic carcinoma show a similar cellular differentiation, EMA-positive epithelial cells in thymoma with no relation to gland-like configurations might represent a pool of cells having a latent potential for malignant disease and might be transformed into thymic carcinoma cells under certain conditions. Immunolabeling for EMA appears to be a useful tool for determining the degree of malignant disease among thymic epithelial neoplasms.

The utility of immunocytochemistry in invasive adenocarcinoma of the cervix

The purpose of the study was to evaluate the utility of immunocytochemistry in the management of cervical adenocarcinoma. Patterns of reactivity to various immunocytochemical markers were correlated with clinically known risk factors for recurrence. A retrospective evaluation of 55 patients with invasive cervical adenocarcinoma was conducted. Monoclonal antibodies were generated against various human intermediate filament proteins and tested on fixed, paraffin-embedded tissue by the avidin-biotin complex immunoperoxidase method. Dako V9 antivimentin antibodies and two anticytokeratin antibodies, 35 beta H11 and 34 beta E12, were used. Polyclonal antibodies to carcinoembryonic antigen and antibodies to epithelial membrane antigen were used. Of 55 patients, 50 (91%) had positive epithelial membrane antigen antibodies in tumor cells. Tissue from patients with cervical adenocarcinoma demonstrated positivity for 35 beta H11 antibodies in 46 of 53 patients (87%) and positivity for 34 beta E12 antibodies in 15 of 54 patients (28%). Vimentin antibodies were negative in all except one patient. Carcinoembryonic antigen-positive antibodies were detected in 37 of 55 patients (67%). This study also demonstrated consistent negative expression of vimentin in invasive cervical adenocarcinoma. Carcinoembryonic antigen expression rates were 50% and 75% for patients with small tumors (less than or equal to 2 cm) and large tumors (greater than 2 cm), respectively (p less than 0.01). Patients with carcinoembryonic antigen expression are at increased risk for recurrence and also sustain reduced survival potential. Patients with cervical adenocarcinoma and carcinoembryonic antigen expression are at increased risk for recurrence. We speculate that immunocytochemistry may detect lymph node micrometastases otherwise unsuspected by conventional microscopy.

Clear cell tumors of minor salivary gland origin: An immunohistochemical and ultrastructural analysis

Three cases of monophasic glycogen-rich clear cell tumors of palatal gland origin were examined immunohistochemically and ultrastructurally in attempts to characterize their cellular composition. Despite their histologic resemblances, the clear cells from each case showed different immunohistochemical features. In case 1 the extensive positivity for vimentin and S- 100 protein, in addition to the focal expression of actin and glial fibrillary acidic protein, strongly suggested that the clear cells were myoepithelial in nature. In contrast, the clear cells from case 2 exhibited both keratin and epithelial membrane antigen positivity, as well as ultrastructural features that suggested that they were glandular epithelial in nature. In case 3 no special markers except for keratin could be detected, indicating the less differentiated nature of the clear cells. These results show the heterogeneity of the clear cell tumor group of minor salivary glands.

Primary cutaneous mucoepidermoid carcinoma: report of a case

Primary mucoepidermoid carcinomas of the skin are extremely rare tumors. We describe a primary cutaneous mucoepidermoid carcinoma arising in the right ear (posterior mid helix) of a 66-year-old white man. The tumor was 0.6 cm in diameter, ulcerated and nonencapsulated. No other tumors were found in the patient. Histologically the tumor showed the characteristics of a "low grade" mucoepidermoid carcinoma, consisting of lobules of polygonal cells with vesicular nuclei. In the center of the lobules were large vacuolated cells (goblet cells). Transitions between the two cell populations were present throughout the tumor. An epidermal attachment of the tumor, as well as epidermal dysplasia, predominantly at the acrosyringium was present, consistent with the theory of sweat duct histogenesis of these tumors. Immunoperoxidase staining showed positivity for epithelial membrane antigen, keratin and carcinoembryonic antigen. The latter was predominantly positive in the goblet cells. Cutaneous metastasis of mucoepidermoid carcinomas with epidermal attachment has been reported. Our case showed only ear involvement and follow-up at 8 months has revealed no evidence of recurrence. These findings are consistent with the diagnosis of primary cutaneous mucoepidermoid carcinoma.

Pancreatic mucinous cystadenocarcinoma with pseudosarcomatous mural nodules. A report of a case with immunohistochemical study

A case of pancreatic mucinous cystadenocarcinoma (PMC) with two pseudosarcomatous mural nodules (PMN) is described. These nodules have not been previously described in this type of tumor. In ovarian mucinous tumors (OMT), similar nodules have been reported, the nature of which has been discussed in detail. Here the similarity between the tumor described here and ovarian tumors is stressed. The immunohistochemical study carried out disclosed in the nodules strong positive staining for vimentin and moderate positivity for keratin and epithelial membrane antigen. These findings, along with histologic details, favor the epithelial nature of the nodules. It was concluded that the nodules are foci of anaplastic carcinoma with high proliferative cell rate, which could explain the coexpression of vimentin and keratin.

Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations

The authors report three cases of sarcomatoid carcinoma arising in the stomach. This uncommon tumor is characterized by a mixture of malignant epithelial and spindle cell elements. All three tumors were large (average diameter, 5 cm) and infiltrated deep into the stomach wall. Two of the tumors had a polypoid configuration; the third was ulcerated and endophytic. Intestinal metaplasia was present adjacent to the tumor in all cases, with dysplasia in two. Immunohistochemical studies showed positivity for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen in the epithelial component of all tumors, and Leu-M1 was positive in the epithelial component of one. The spindle cell components contained vimentin, and in tumor 2, the spindle cell component was also positive for desmin. Two tumors showed focal positivity for cytokeratin in the spindle cells immediately adjacent to the epithelial component. Ultrastructurally, the spindle cell component of two tumors was composed of undifferentiated cells without specific epithelial or mesenchymal features. The third tumor contained occasional cells with features of myofibroblasts.

A Case of Malignant Rhabdoid Tumor Arising from Soft Parts in the Prepubic Region

An extrarenal malignant rhabdoid tumor arising from soft parts in the prepubic region of a 37-year-old man is described. This case appears to be unusual with regard to its location and age at onset. To our knowledge, the patient is the oldest recorded in whom such a lesion has arisen. Histologically, the tumor consisted of an admixture of polygonal and elongated cells with abundant eosinophilic cytoplasm frequently containing hyaline-like globules. Ultrastructurally, these cytoplasmic inclusions were compatible with intermediate filaments. Immunohistochemical staining disclosed keratin (non-squamous epithelial type) and epithelial membrane antigen positivity. These characteristic features were identical to malignant rhabdoid tumor of the kidney seen in infants and young children. This extrarenal malignant rhabdoid tumor showed an aggressive clinical course, although its exact histogenesis was unclear.

Immunohistochemical distribution of epithelial membrane antigen in bladder carcinomas as detected with a monoclonal antibody.

Expression of epithelial membrane antigen (EMA) was investigated immunohistochemically in 27 cases of bladder carcinoma using a monoclonal antibody. Normal urothelial epithelium showed EMA staining restricted to the upper layer of the surface epithelium. G-I transitional cell carcinomas demonstrated positive EMA staining which could be divided into the following 3 types; type 1, in which highly stained cells occurred in the upper layer of the neoplastic epithelium; type 2, in which the whole tumour focus was slightly stained; and type 3, in which cells strongly positive for EMA were scattered throughout the tumour focus. G-III (undifferentiated) transitional cell lesions exhibited irregular expression of EMA whereas squamous cell demonstrated specific intense EMA staining within keratinized tumour cells.

Solitary Circumscribed Neuroma of the Skin (So-called Palisaded, Encapsulated Neuroma)

Solitary, circumscribed neuroma is a distinctive benign cutaneous tumor that was first described under the name "palisaded, encapsulated neuroma" over 15 years ago. Despite the fact that it is not uncommon, it has received minimal attention and is very poorly known among pathologists. We have studied the clinicopathologic and immunohistochemical features of 39 cases. These lesions almost always present on the face or close to a mucocutaneous junction in middle-aged adults. Most examples measure less than or equal to 0.5 cm and are composed of a partially encapsulated mass of bland Schwann cells and innumerable tiny axons arranged in interlacing fascicles. The capsule is composed of perineural cells that show epithelial membrane antigen positivity. Solitary, circumscribed neuroma is not associated with von Recklinghausen's neurofibromatosis, nor is there evidence to support its possible relationship to the type IIb multiple endocrine neoplasia syndrome. This entity warrants wider recognition.

Immunohistochemical characterization of chondroid syringomas.

This study was initiated because the histogenesis of chondroid syringomas (CSs), especially the role of the myoepithelial cells, is still controversial. Twelve cases of CS were analyzed by immunohistochemical methods with a broad panel of routinely used antibodies. The epithelial elements were classified as tubuloglandular components, stromal cells, and solid nests. The authors' results indicated the following: (1) The inner cell layers of tubuloglandular components have distinct epithelial features with cytokeratin (CK), carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA) positivity. (2) The outer cell layers had negative results for muscle-specific actin (MSA), desmin, CEA, EMA, and CK (if antibody AE1/3 was used) and had positive results for vimentin, S-100 protein, neuron-specific enolase (NSE), and in three cases for glial fibrillary acidic protein (GFAP). (3) The stromal cells and, to a lesser extent, the solid nests expressed immunophenotypes similar to those of the outer cell layers. These data suggest that the stromal components may derive from the outer cells of the tubuloglandular elements but derive from the outer cells of the tubuloglandular elements but do not confirm their exclusive myoepithelial origin.

Primary cutaneous leiomyosarcoma. A histological and immunohistochemical study of 9 cases, with ultrastructural correlation

Leiomyosarcoma (LMS) of dermal and subcutaneous tissues is an uncommon neoplasm. In order to analyze the specialized pathologic features of this tumor, we undertook a histological, ultrastructural, and immunohistochemical study of 9 superficial LMS, including 7 dermal lesions and 2 subcutaneous neoplasms. These were compared with 12 examples of "deep" extracutaneous LMS. Metastases to the skin from two of the latter neoplasms were also examined. Immunohistochemistry was found to be a useful diagnostic adjunct to light microscopic and ultrastructural studies in that all LMS coexpressed vimentin and desmin, regardless of site, and 90% also expressed muscle-specific actin. Variable expression of cathepsin B and myelin basic protein was noted in 8 and 10 tumors, respectively, whereas none contained cytokeratin. Weak cytoplasmic positivity for epithelial membrane antigen was seen in 1 dermal and 3 extracutaneous LMS. Of 7 dermal LMS, 4 contained S-100 protein, whereas this determinant was found in only 1 of 12 extracutaneous tumors. Conversely, Leu 7 reactivity was present in 7 of 12 extracutaneous LMS, but only 2 of 9 superficial lesions. Review of clinical features confirmed that subcutaneous LMS is capable of aggressive behaviour, whereas dermal LMS was more likely to behave in an indolent fashion. However, one example of dermal LMS exhibited aggressive local recurrences and distant metastasis, ultimately leading to the death of the patient. Therefore, careful clinical followup is indicated in all cases.

Spindle-cell and pleomorphic neoplasms of the skin. A clinicopathologic and immunohistochemical study of 30 cases, with emphasis on "atypical fibroxanthomas".

Atypical fibroxanthoma belongs to the family of spindle-cell and pleomorphic neoplasms of the skin. The lineage of differentiation of this tumor and the means whereby it can be diagnostically separated from other similar morphologic entities have been controversial. In order to address these issues, the authors studied 30 spindle-cell and/or pleomorphic cutaneous tumors, including atypical fibroxanthomas (AFXs), superficial malignant fibrous histiocytomas (MFHs), dermatofibrosarcoma protuberans (DFSPs), sarcomatoid squamous-cell carcinomas (SCCs), spindle-cell malignant melanomas (MMs), and leiomyosarcomas, (LMSs). These cases were analyzed using a panel of eight antibodies and the immunoperoxidase technique. AFXs were reactive for vimentin, alpha-1-antichymotrypsin (AACT), alpha-1-antitrypsin (AAT), and cathepsin-B (CB) but failed to display cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, and desmin. MFHs and DFSPs exhibited immunophenotypic profiles that were nearly identical to that just described. In contrast, SCCs were typified by positivity for CK and EMA; MMs exhibited uniform reactivity for S-100 protein; and LMSs contained desmin in four of five cases. A surprising result was the expression of S-100 by LMSs. Also, all tumors displayed at least one of the three proteolytic enzymes assessed in this study (AAT, AACT, and CB), demonstrating the relative diagnostic nonspecificity of these determinants. It is concluded that AFXs are "fibrohistiocytic" neoplasms, with substantial morphologic and immunohistochemical similarity to MFHs. The immunohistochemical classification of spindle-cell and pleomorphic tumors of the skin necessitates the use of antibody panels to assess the presence of markers that are characteristic of each diagnostic group.

Immunohistochemical Identification of Epithelial Membrane Antigen in Sweat Gland Tumours by the Use of a Monoclonal Antibody

A total of 78 cases of adnexal tumors of the skin were examined with the use of monoclonal antibody against epithelial membrane antigen (EMA). The EMA reaction was confined to luminal surfaces and lateral borders of sweat glands, both eccrine and apocrine, being usually absent in ductal segments. Neoplastic lesions of all the adenomatous tumours and mixed tumours of sweat glands showed specifically positive EMA staining of luminal surfaces and lateral borders of tubular, duct-like, and cystic structures. However, solid foci of those tumours were negative for EMA. Tumours of ductal origin, e.g. syringomas and poromas, exhibited positive EMA staining in their plasma membrane, although normal intact keratinocytes did not stain for EMA. Immunohistochemical distribution of EMA in skin adnexal tumours was classified into two types: one in which the luminal surfaces and lateral outer borders were positive, similar to that of the normal secretory coil, and the other in which the plasma membrane of neoplastic cells of ductal origin was positive.

Immunohistochemical observations on binding of monoclonal antibody to epithelial membrane antigen in epithelial tumors of the oral cavity and skin

A total of 211 cases of benign and malignant tumors of epithelial origin were studied by the immunoperoxidase method to determine the distribution profile of epithelial membrane antigen (EMA) with the use of monoclonal antibody. Normal epithelial cells in the oral mucosa and skin were usually negative for EMA staining, as were epithelial cells in hyperplastic lesions and papillomas. Paget cells and tumor cells of Bowen's disease (carcinoma in situ) demonstrated a high incidence of EMA positivity, whereas the frequency in basal cell carcinoma was unexpectedly low. Squamous cell carcinomas revealed positive EMA staining of cytoplasmic membranes, and the antigen was also present in keratinized areas. EMA expression in squamous cell carcinoma generally showed a high incidence (85%) and was higher in keratinized lesions than in unkeratinized or less well-differentiated neoplasms. EMA distribution could be classified into two forms: one in which the cytoplasmic membranes demonstrate positivity and in which a positive cytoplasmic pattern is found in parakeratinized cells in malignant foci.

Immunohistochemical Identification of Epithelial Membrane Antigen in Sweat Gland Tumours by the Use of a Monoclonal Antibody

A total of 78 cases of adnexal tumours of the skin were examined with the use of monoclonal antibody against epithelial membrane antigen (EMA). The EMA reaction was confined to luminal surfaces and lateral borders of sweat glands, both eccrine and apocrine being usually absent in ductal segments. Neoplastic lesions of all the adenomatous tumours and mixed tumours of sweat glands showed specifically positive EMA staining of luminal surfaces and lateral borders of tubular, duct-like, and cystic structures. However, solid foci of those tumours were negative for EMA. Tumours of ductal origin e.g. syringomas and poromas, exbibited positive EMA staining in their plasma membrane, although normal intact keratinocytes did not stain for EMA. Immunohistochemical distribution of EMA in skin adnexal tumours was classified into two types: one in which the luminal surfaces and lateral outer borders were positive, similar to that of the normal secretory coil, and other in which the plasma membrane of neoplastic cells of ductal origin was positive.

Placental-like alkaline phosphatase reactivity in human tumors: An immunohistochemical study of 520 cases

Placental-like alkaline phosphatase (PLAP) activity has been reported in various human neoplasms of both somatic and germ cell types. The expression of PLAP was examined with a polyclonal antibody and the immunoperoxidase technique in formalin-fixed, paraffin-embedded sections of 37 germ cell neoplasms and 483 somatic tumors. The expression of keratin and epithelial membrane antigen (EMA) was concurrently assessed to determine whether these stains were helpful in distinguishing germ cell neoplasms from somatic tumors that might mimic them microscopically. All germ cell lesions were reactive for PLAP, but so were 62 somatic carcinomas, usually in female müllerian, intestinal, and lung cancers and less often in carcinomas of the breast and kidney. PLAP-reactive somatic tumors exhibited EMA and keratin positivity in the absence of prior protease digestion, whereas germ cell neoplasms failed to do so. Malignant mesotheliomas were nonreactive for PLAP, as were carcinomas of the nasopharynx, adrenals, liver, pancreas, stomach, prostate, and urinary bladder. PLAP is a highly sensitive but nonspecific immunohistologic marker of germ cell differentiation. However, non-protease-enhanced stains for keratin and EMA allow separation of germ cell and somatic carcinomas, despite their shared capacity for PLAP expression. In somatic neoplasms, PLAP immunoreactivity might be of potential use in predicting possible primary sources for metastatic tumors of unknown origin.

Epithelial membrane antigen—A diagnostic discriminant in surgical pathology: Immunohistochemical profile in epithelial, mesenchymal, and hematopoietic neoplasms using paraffin sections and monoclonal antibodies

Glycoproteins isolated from human milk fat globule membranes, designated epithelial membrane antigen (EMA), have been detected immunohistochemically in most nonneoplastic epithelia and are potentially a highly effective marker for establishing the epithelial nature of neoplastic cells. With commercially available monoclonal antibodies and an indirect immunoperoxidase technique, EMA localization was evaluated in paraffin-embedded tissues from a wide variety of neoplasms (320 specimens). Adenocarcinomas from various primary sites (breast, lung, colon, stomach, pancreas, gallbladder, prostate, endocrine glands, ovary, kidney, thyroid) were immunoreactive for EMA in 88 of 97 cases (91 per cent). Cytoplasmic and apical luminal membrane staining were the most common patterns of immunoreactivity, with peripheral membrane staining or other patterns also seen in some neoplasms. Squamous cell (13 of 13 cases) and transitional cell (12 of 12 cases) carcinomas, small cell anaplastic carcinomas (12 of 12 cases), and mesotheliomas (six of six cases) were also uniformly EMA-positive. Malignant lymphomas of the Hodgkin's (15 cases) and non-Hodgkin's types (74 cases), except for the true histiocytic lymphomas and occasional T-cell lymphomas, were nonreactive for EMA. Neoplastic and nonneoplastic plasma cells showed variable EMA positivity. Endocrine neoplasms (17 cases), including carcinoid tumors, medullary carcinoma of thyroid, adrenocortical carcinomas and pheochromocytomas, and germ cell tumors (eight cases, embryonal carcinoma and seminoma), and a wide variety of soft tissue tumors (27 cases) generally lacked immunoreactivity for EMA; the exceptions to this finding were synovial sarcomas and an epithelioid sarcoma. Malignant melanomas (eight cases) were typically nonreactive. Based on the observations in this large series of neoplasms, EMA is an excellent marker of epithelial differentiation, appears to be highly reliable for discriminating between poorly differentiated carcinomas and malignant lymphomas, and is especially helpful in characterizing small cell anaplastic carcinomas. Epithelial membrane antigen immunoreactivity is well preserved in paraffin sections of routinely processed tissues, facilitating application of this technique in diagnostic surgical pathology.