Analysis of the tumour-associated antigen TAG-12 by monoclonal antibody 7A9 in normal,benign and malignant mammary tissues

Summary A monoclonal antibody 7A9 was raised against the tumour-associated glycoprotein TAG-12 purified from T47-D breast carcinoma cells. In immunoblots from cytosol of T47-D cells and from sera of breast cancer patients, antibody 7A9 detects the high molecular weight mucin-like TAG-12 antigen. A series of paraffin sections of normal, benign and malignant mammary tissues have been studied with monoclonal antibody 7A9 and the immunoalkaline phosphatase method. In resting gland, proliferating gland and fibroadenoma ducts, reactivity of 7A9 was mainly restricted to luminal membranes of epithelial cells and secretions. 77/79 primary breast carcinomas including ductal, lobular and various other carcinoma types showed cytoplasmic and/or membrane-associated staining with 7A9 in most tumour cells. Metastases (31/31) from different sites were also positive. Strong immunoreactivity with single tumour cells was noted in cytological preparations from freshly resected breast cancer tissue. Thus, monoclonal antibody 7A9 seems to be very useful for the targeting of breast carcinoma cells.     

Use of a monoclonal antibody (B72.3) as a novel immunohistochemical adjunct for the diagnosis of carcinomas in fine needle aspiration biopsy specimens

Monoclonal antibody B72.3 has been shown to be reactive with a high-molecular-weight glycoprotein complex termed TAG(tumor-associated glycoprotein)-72. By the avidin-biotin immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumor tissues from both malignant and benign tissues were analyzed for TAG-72 expression. Staining (range, 1 to 100 per cent of tumor cells) with monoclonal antibody B72.3 was observed in needle aspirates from 18 of 18 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, and six of six adenocarcinomas of the colon, as well as adenocarcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, and sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid, and thyroid also failed to stain. In 66 patients, tumor-bearing tissue had also been resected and was available for comparative examination with monoclonal antibody B72.3. In 62 of these 66 patients, the staining patterns in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tissues. From these studies it is concluded that monoclonal antibody B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells but not in benign cells and is most selectively expressed in adenocarcinomas. This monoclonal antibody may be used as a novel adjunct for the diagnosis of carcinoma in fine needle aspiration biopsy specimens.     

Distribution of BCA-225 in adenocarcinomas. An immunohistochemical study of 446 cases

BCA-225 is a glycoprotein identified in human breast carcinoma cells that has been reported to show a restricted distribution in other human tissues. To further define the presence of BCA-225 in human carcinomas, the authors performed an immunohistochemical study, applying a commercially available monoclonal antibody to BCA-225 to formalin-fixed, paraffin-embedded sections of 446 adenocarcinomas from a variety of sites. BCA-225 expression was found to be common in adenocarcinomas of the breast (98%), kidney (94%), ovary (80%), and lung (74%) but was infrequent in adenocarcinomas of the gastrointestinal tract (10-16%). Adenocarcinomas of the prostate, bile ducts, thyroid, endometrium, endocervix, and pancreas showed an intermediate frequency of BCA-225 expression (36-68%). Although rare tumor cells in three hepatocellular carcinomas showed reactivity for BCA-225, staining of more than 10% of the tumor cells was not seen in any of the 23 hepatocellular carcinomas that were studied. The authors conclude that BCA-225 is expressed commonly in human adenocarcinomas and that it is not a breast-specific antigen. Antibodies to BCA-225 may have utility in helping one to exclude hepatocellular carcinoma in certain clinical settings.     

Conserved antigen expression in epithelial tumors recognized by monoclonal antibody 4A9 generated against canine mammary carcinoma cells

Hybridoma-derived murine monoclonal antibodies (MoAbs) were generated by fusing P3X63-Ag8.653 myeloma cells with splenic cells from BALB/c mouse which had been immunized with viable canine mammary adenocarcinoma cells, CMT-2. Fifteen MoAbs were shown to react with immunizing cells in indirect immunofluorescence (IFA) and enzyme-linked immunosorbent (ELISA) assays. The reactivity of one IgM MoAb, designated 4A9, was evaluated. The antigen recognized by 4A9 on CMT-2 cells appeared to be localized both in cell membrane and cytoplasm against fixed and unfixed preparations by IFA. The 4A9 MoAb was found to bind with four of five canine mammary carcinoma cell lines while no binding was detected with normal fibroblastic cell lines. In vivo tissue distribution of 4A9 antigen was evaluated by indirect immunoperoxidase (IP) assay against formalin-fixed, paraffin-embedded sections of normal and neoplastic tissues. 4A9 MoAb reacted strongly to moderately with 75% of mammary carcinomas, moderately to weakly with 57% of benign mammary tumors, and strongly with squamous cell and perianal gland carcinomas (100%), interstitial cell tumors (100%), transitional cell carcinomas (43%), lung adenocarcinomas (40%), colon carcinomas (33%), and pancreatic adenocarcinomas (20%). Moderate to weak staining was detected with granulosa cell tumors (25%) and apocrine gland adenocarcinomas (50%). Strong reactivity with perianal gland carcinomas contrasted to no reactivity with perianal gland adenomas. No immunostaining was detected with a large variety and number of normal adult and fetal tissues tested; negligible and very restricted staining was observed in a few adult and fetal tissues. Normal mammary gland was negative. Since the antigen is expressed on the cell surface and in the cytoplasm of most mammary carcinoma cells and a variety of other epithelial tumor cells, the 4A9 antibody may have potential application in diagnosis and management of canine mammary cancer and a variety of other epithelial tumors.     

Reactivity of a monoclonal antibody with tissues and tumors from the human breast. Immunohistochemical localization of a new antigen and clinicopathologic correlations.

The reactions of a monoclonal antibody to the MCF7 breast cancer cell line were immunohistochemically studied on a variety of breast tumors, primary and metastatic, on mammary epithelium and on nonneoplastic breast lesions. A high proportion of positive reactions was observed in ductal, lobular, and tubular carcinomas as well as in mammary Paget's disease. Mucinous, medullary, and papillary carcinomas showed a low incidence of reactivity. Carcinomas with metaplasia, carcinoids, and nonepithelial breast tumors were unreactive with the antibody. Positive immunostaining was documented also in nodal and extranodal metastatic lesions. The staining of nodal metastases was correlated with the positive reaction of the primary tumor. Reactivity was widely distributed in normal breast epithelial cells and in benign breast lesions. Staining of nonneoplastic mammary epithelial was associated with reactivity of adjacent neoplastic tissues. Staining differences between nonneoplastic and neoplastic mammary tissues were related to the intensity and cytologic distribution of the labeling. Heterogeneous reactivity of morphologically similar cells was documented in nonneoplastic and neoplastic breast epithelial cells as well as in nodal and extranodal breast carcinoma metastases. Immunohistologically detectable antigen was not correlated with prognostic factors such as histologic grade or nodal status. A retrospective study of T1NO cases failed to substantiate any prognostic value for the reactivity of primary breast tumors with this monoclonal antibody.     

Malignant mesotheliomas. Improved differential diagnosis from lung adenocarcinomas using monoclonal antibodies 44-3A6 and 624A12.

Forty-three malignant pleural mesotheliomas and 10 known metastatic pulmonary adenocarcinomas to the pleura were studied by immunohistochemistry using monoclonal antibodies 44-3A6 and 624A12. Monoclonal antibodies 44-3A6 and 624A12 were raised against human pulmonary carcinoma cell lines; they recognize a membrane-associated protein of 40,000 mol wt and a specific sugar sequence of lacto-N-fucopentose III, respectively. Samples were also studied with a broad-spectrum antikeratin antibody and a polyclonal antibody to carcinoembryonic antigen (CEA). These investigations were performed on formalin-fixed and paraffin-embedded tissues. The mesotheliomas comprised only grossly evident, pleurectomized, or pneumonectomized cases; they included 22 epithelial, 15 biphasic, and 6 spindle cell types. Electron-microscopic study was also done on 9 cases. None of the mesotheliomas was immunoreactive to 624A12, while 9/10 metastatic pulmonary adenocarcinomas were convincingly immunoreactive. Monoclonal antibody 44-3A6 immunostained all of the metastatic adenocarcinomas strongly, whereas only 10/43 mesotheliomas were focally and weakly immunoreactive. The latter included 5 epithelial and 4 biophasic mesotheliomas and 1 spindle cell mesotheliomas; the immunoreaction was confined to scattered single cells, and the staining pattern was readily discernible from that of adenocarcinomas. Forty of 43 mesotheliomas were strongly immunoreactive with the broad-spectrum anti-keratin antibody, whereas 8/10 metastatic pulmonary adenocarcinomas showed focal and rather weak staining. Seven of 10 metastatic adenocarcinomas were immunoreactive to anti-CEA antibody, while only 15/43 mesotheliomas displayed weak immunoreactivity. It is concluded that monoclonal antibodies 44-3A6 and 624A12 are excellent phenotypic markers of metastatic pulmonary adenocarcinomas to the pleura and thus are useful for the differential diagnosis of pleural mesotheliomas. Given conventionally fixed and processed tissues, it appears that the combined use of these monoclonal antibodies may be more effective for that differential diagnosis than anti-CEA and anti-keratin antibodies.     

Immunohistochemical demonstration of nonspecific cross-reacting antigen in normal and neoplastic human tissues using a monoclonal antibody. Comparison with carcinoembryonic antigen localization

Nonspecific cross-reacting antigen (NCA) immunoreactivity was localized in normal and neoplastic human tissues using a monoclonal antibody to 55, 90 and 95 kDa molecules of NCA. This was compared to the localization of immunoreactive carcinoembryonic antigen (CEA) as demonstrated by polyclonal and monoclonal antibodies. In frozen sections, CEA was localized in normal surface epithelium of the stomach and colon where NCA was only weakly detected. Type 1 and type 2-like pneumocytes were positive for NCA, while CEA was localized only in type 2-like pneumocytes. CEA and NCA were both demonstrated in ductal cells of frozen pancreatobiliary and mammary tissues. The antigenicity of CEA and NCA in normal tissues was significantly lost after paraffin embedding as compared to frozen sections. NCA was consistently demonstrated in eccrine sweat glands embedded in paraffin. In various tumor tissues, CEA and NCA were colocalized and expression increased sufficiently to be detected in paraffin sections. Adenocarcinomas of the stomach and colon and cystadenocarcinoma of the pancreas, as well as neuroendocrine carcinomas of the lung and thyroid, showed a CEA predominance over NCA. In ductal adenocarcinomas of the pancreas and breast and in cholangiocarcinoma, NCA reactivity was greater than CEA. Keratinizing foci of most squamous cell carcinomas of mucosal origin and some adenocarcinomas equally expressed both. Hepatocellular carcinoma, lobular mammary carcinoma and papillary thyroid carcinoma were positive only with unabsorbed polyclonal antibody which widely recognizes CEA-related substances. Renal cell carcinoma, prostatic adenocarcinoma, transitional cell carcinoma, anaplastic carcinomas, choriocarcinoma and basal cell carcinomas showed little or no immunoreactivity. Hence the relative ratio of CEA/NCA expression in tumors was dependent on the tissue of origin and histologic type. The cytoplasmic granular staining of NCA in cancer cells was a noteworthy difference from the plasma membrane-associated localization of CEA.     

Anti-Leu 7 immunoreactivity with human tumours: its value in the diagnosis of prostatic adenocarcinoma

The reactivity of the anti-Leu 7 monoclonal antibody (Leu 7) was tested on 83 human tumours and on non-neoplastic prostatic, hepatic and pancreatic tissues. A four-step peroxidase-anti-peroxidase method was used on paraffin embedded tissues and we observed strong cytoplasmic positivity in all 19 primary prostatic tumours, in two metastatic, poorly differentiated prostatic adenocarcinomas, and in normal and hypertrophic prostatic epithelium. All the primary prostatic tumours also stained positively for prostate-specific antigen and for prostatic acid phosphatase using polyclonal antisera. The degree of positivity for these antigens varied from case to case. Adenocarcinomas arising from the gastrointestinal tract, pancreas and gallbladder were anti-Leu 7 negative. Focal Leu 7 positivity, largely confined to cell membranes, was observed in some ovarian, endometrial, renal, lung and breast adenocarcinomas. These tumours, as well as some of the gastrointestinal, hepatic and pancreatic tumours, also showed focal cytoplasmic positivity for prostate-specific antigen and prostatic acid phosphatase. Our findings suggest that the anti-Leu 7 monoclonal antibody is a marker that may facilitate the detection of metastatic prostatic adenocarcinoma, especially when used in conjunction with staining for prostate-specific antigen.     

Immunohistochemical Demonstration of Nonspecific Cross-reacting Antigen in Normal and Neoplastic Human Tissues Using a Monoclonal Antibody: Cornparison with Carcinoembryonic Antigen Localization

Nonspecific cross-reacting antigen (NCA) immunoreactivity was localized in normal and neoplastic human tissues using a monoclonal antibody to 55, 90 and 95 kDa molecules of NCA. This was compared to the localization of immunoreactive carcinoembryonic antigen (CEA) as demonstrated by polyclonal and monoclonal antibodies. In frozen sections, CEA was localized in normal surface epithelium of the stomach and colon where NCA was only weakly detected. Type 1 and type 2 like pneumocytes were positive for NCA, while CEA was localized only in type 2-like pneumocytes. CEA and NCA were both demonstrated in ductal cells of frozen pancreatobiliary and mammary tissues. The antigenicity of CEA and NCA in normal tissues was significantly lost after paraffin embedding as compared to frozen sections. NCA was consistently demonstrated in eccrine sweat glands embedded in paraffin. In various tumor tissues, CEA and NCA were colocalized and expression increased sufficiently to be detected in paraffin sections. Adenocarcinomas of the stomach and colon and cystadenocarcinoma of the pancreas, as well as neuroendocrine carcinomas of the lung and thyroid, showed a CEA predominance over NCA. In ductal adenocarcinomas of the pancreas and breast and in cholangiocarcinoma, NCA reactivity was greater than CEA. Keratiniring foci of most squamous cell carcinomas of mucosal origin and some adenocarcinomas equally expressed both. Hepatocellular carcinoma, lobular mammary carcinoma and papillary thyroid carcinoma were positive only with unabsorbed polyclonal antibody which widely recognizes CEA-related substances. Renal cell carcinoma, prostatic adenocarcinoma, transitional cell carcinoma, anaplastic carcinomas, choriocarcinoma and basal cell carcinomas showed little or no immunoreactivity. Hence the relative ratio of CEA/NCA expression in tumors was dependent on the tissue of origin and histologic type. The cytoplasmic granular staining of NCA in cancer cells was a noteworthy difference from the plasma membrane-associated localization of CEA. Acta Pathol Jpn 40: 85–97, 1990.     

Monoclonal antibody to a human pancreatic carcinoma cell line recognizes gastrointestinal neoplasms.

A monoclonal antibody designated RWP1.1 was produced against a human pancreatic carcinoma cell line RWP1. This antibody was shown to recognize an epitope of carcinoembryonic antigen. The reactivity of the antibody was evaluated on formalin-fixed normal tissues, 86 malignant neoplasms, 10 colonic polyps, and 6 cases of chronic pancreatitis using the peroxidase anti-peroxidase technique. RWP1.1 did not react with normal tissues apart from weak staining of fetal pancreatic ducts. This antibody preferentially reacted with primary and metastatic adenocarcinomas of the colon, stomach, pancreas, and colonic polyps but not with most adenocarcinomas from other sites nor with other types of tumors or cases of chronic pancreatitis. It also reacted with colon adenocarcinomas on frozen sections. The restricted specificity of this antibody could be used in differentiating gastrointestinal adenocarcinomas from other types of tumors including adenocarcinomas from other sites and most pancreatic adenocarcinomas from chronic pancreatitis.     

Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors

We have defined a human breast tumor associated antigen using a murine monoclonal antibody (MAb DF3) prepared against a membrane-enriched fraction of a human breast carcinoma. This antigen has a MW of 290 kD and is detectable on the cell surface of human breast carcinoma cells using a live cell radioimmunoassay and fluorescence flow cytometry. More important, immunoperoxidase staining with MAb DF3 clearly distinguishes malignant and benign breast lesions. A cytoplasmic staining pattern has been observed with 40 of 51 (78%) breast carcinomas, but only one of 13 fibroadenoma or fibrocystic disease specimens. In contrast, reactivity of benign breast lesions with MAb DF3 primarily occurs along apical borders on ductules. These results demonstrate that the DF3 antigen is present on apical borders of more differentiated secretory mammary epithelial cells and in the cytosol of less differentiated cells.     

Immunohistochemical reactivity of a monoclonal antibody prepared against human breast carcinoma

Summary The reactivity profile of an IgM monoclonal antibody, MBR1, raised against the human breast cancer cell line MCF7, was studied in a variety of human tumours and non-neoplastic tissues by light microscopic immunohistochemistry. The range of reactivity included specific types of non-neoplastic epithelial cells and a number of epithelial tumours. Most mammary carcinomas reacted with MBR1, but adenocarcinomas and squamous carcinomas from different sites were also strongly positive. Different patterns of immunoreactivity were apparent in microscopically normal tissues, in tissues with inflammatory changes and in carcinomas. Heterogeneous staining, despite morphological similarities, was documented in neoplastic and non-neoplastic epithelial cells. The reactivity of MBR1 was different from that reported for other monoclonal antibodies, but revealed similarities to that of monoclonal antibodies and polyclonal sera against human milk fat globule membrane.     

Prostatic adenocarcinoma. Evaluation of immunoreactivity to monoclonal antibody B72.3

Monoclonal antibody B72.3 reacts with a tumor-associated glycoprotein designated TAG-72 that is expressed in many adenocarcinomas but not in normal tissues. The authors evaluated the immunoreactivity of B72.3 to benign, hyperplastic prostate, and to primary adenocarcinoma of the prostate to determine the frequency of TAG-72 production by benign and malignant prostatic epithelium. Focal cytoplasmic staining of gland cells was seen in 19 of 20 cases of glandular hyperplasia, and weak, homogeneous staining of secretions was seen in five cases. In contrast, 27 of the 35 (77%) adenocarcinomas studied showed at least focal intense staining of secretions, and 30 (86%) of the tumors showed some cytoplasmic immunostaining with B72.3. Positive staining occurred in all of the well-differentiated adenocarcinomas (100%) but was seen less often in moderately differentiated (82%) and poorly differentiated adenocarcinomas (58%). Because benign gland cells may express the TAG-72 antigen, immunohistochemistry results must be interpreted with caution and with regard to the overall morphologic pattern. Nonetheless, a positive B72.3 immunostain may be useful in identifying adenocarcinoma of the prostate, especially when an intense luminal reaction is found. A negative stain does not exclude the presence of adenocarcinoma, however.     

Immunocytochemical distribution of a breast carcinoma associated glycoprotein identified by monoclonal antibodies.

A glycoprotein, BCA-225 (Mr 225,000-250,000), has been identified in cells and spent medium of clone 11 T47D breast carcinoma cells by three murine monoclonal antibodies, CU18, CU26, and CU46. The antigen was localized in paraffin sections of 167/178 (94%) Bouin's-fixed human breast carcinoma tissues and few other carcinomas (1/8 lung [squamous], 4/4 uterine cervix) in an intracellular pattern, whereas an apical or glycocalyx distribution was seen in several normal tissues, benign lesions, and malignant tumors. Although the immunocytochemical staining patterns observed with these antibodies have many similarities to those described with other previously reported monoclonal antibodies, notable differences include the lack of reactivity of CU18, CU26, and CU46 with lactating mammary gland and with gastrointestinal malignancies. BCA-225 binds to wheat germ lectin, not to concanavalin A, but monoclonal antibody binding does not appear to involve the carbohydrate component of the molecule. The frequency of the immunocytochemical detection of BCA-225 in breast carcinomas and its restricted distribution in other human tissues suggest considerable clinical potential for this antigen and its corresponding monoclonal antibodies.     

Reactivity spectrum of 30 monoclonal antimelanoma antibodies to a panel of 28 melanoma and control cell lines

Thirty monoclonal antibodies from eight laboratories exchanged after the First Workshop on Monoclonal Antibodies to Human Melanoma held in March 1981 at NIH were tested in an antibody-binding radioimmunoassay using a panel of 28 different cell lines. This panel included 12 melanomas, three neuroblastomas, four gliomas, one retinoblastoma, four colon carcinomas, one lung carcinoma, one cervical carcinoma, one endometrial carcinoma, and one breast carcinoma. The reactivity pattern of the 30 monoclonal antibodies tested showed that none of them were directed against antigens strictly restricted to melanoma, but that several of them recognize antigenic structures preferentially expressed on melanoma cells. A large number of antibodies were found to crossreact with gliomas and neuroblastomas. Thus, they seem to recognize neuroectoderm associated differentiation antigens. Four monoclonal antibodies produced in our laboratory were further studied for the immunohistological localization of melanoma associated antigens on fresh tumor material. In a three-layer biotin-avidin-peroxidase system each antibody showed a different staining pattern with the tumor cells, suggesting that they were directed against different antigens.     

Monoclonal antibody directed against neuroendocrine properties of both normal and malignant cells

A monoclonal antibody, 6H7, was produced by the immunization of small cell carcinoma of the lung (SCCL). Immunohistochemical examination indicated that 6H7 reacted not only with SCCL but also various neuronal and/or endocrine tumors such as neuroblastoma, pheochromocytoma, carcinoid and adrenal cortical tumors. 6H7 was also reactive with normal neuroendocrine tissues including brain, spinal cord, thyroid follicular cells, pancreatic islet cells and adrenal cells. 6H7 did not react with squamous cell carcinomas, one large cell carcinoma or most adenocarcinomas of the lung, or carcinomas of the stomach, colon, pancreas, breast and esophagus. The antigen recognized by 6H7 was analyzed on gel filtration after purification of the antigen by liquid chromatography which indicated the molecular weight of the antigen to be 270,000-300,000. From SDS-PAGE analysis the antigen reactive with 6H7 appeared to consist of polypeptide dimers of 128,000.     

Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti-H731 antibody

The novel gene H731 (approved name: PDCD4 (programmed cell death 4)) has been isolated as an antigen gene of the monoclonal antibody Pr-28 which recognized a nuclear antigen in proliferating cells. The gene is homologous to the mouse gene (MA-3/Pdcd4/A7-1) which was associated with apoptosis and was shown to suppress tumor promoter-induced neoplastic transformation. A polyclonal antibody against H731-protein derived from an extract of Escherichia coli transformed with an H731 expression plasmid was prepared, and the H731-protein expression in human normal and tumor cells using the antibody was studied. The staining patterns of asynchronous cultures of human normal fibroblasts (MRC-5) were heterogeneous but the antigen was accumulated in the nuclei at the G0 phase. On the contrary, the antigen was overproduced and localized in the cytoplasm during the cell cycle in tumor cell lines. Immunohistological studies revealed that the H731-protein was highly expressed in bladder carcinoma and breast carcinoma tissues compared with the normal tissues so far tested. These results indicated that expression of the H731-protein was up-regulated or induced in the proliferative cells. Immunohistological studies also revealed that the protein was abundantly expressed in the small duct epithelial cells of the normal mammary gland.     

A monoclonal antibody, NCRC-11, raised to human breast carcinoma. 1. Production and immunohistological characterization

The production of a mouse monoclonal IgM antibody, NCRC-11, raised against human breast carcinoma is described. It has been characterized immunohistologically. The antigen recognised has a wide but highly specific distribution in normal tissues, being virtually confined to the surface of certain epithelial cell types. It is found in some forms of epithelial metaplasia and most epithelial malignancies, particularly adenocarcinomas. The heterogeneity of staining in mammary carcinomas is outlined and is of particular interest. The immunohistological staining distribution of NCRC-11 is similar to other antibodies, including anti-epithelial membrane antigen, which were raised against human milk fat globule membrane. A competition experiment with some of these antibodies, using a flow cytofluorimeter, showed competition with one antibody, LICR LON/M8.     

Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies.

To evaluate the role of carcinoembryonic antigen (CEA) in solving problems of tumor histogenesis in surgical pathology, monoclonal antibodies to four distinct epitopes of CEA (E-Z-EM) were applied to paraffin sections of 303 epithelial neoplasms from multiple sites. Two epitopes were CEA specific (D14 and B7.1), one was shared with nonspecific cross-reacting antigen (NCA) (B7.8), and the fourth (B18) was common to CEA, NCA, and biliary glycoprotein antigen (BGP). A sample of the tumors (n = 110) was also stained with a polyclonal anti-CEA (DAKO). Gastrointestinal adenocarcinomas, including esophageal and gastric (n = 19), small intestinal (n = 8), colorectal (n = 56), biliary tract (n = 8), and pancreatic adenocarcinomas (n = 14), were consistently positive with all five antibodies. Other predominantly gland-forming carcinomas tested, comprising lung (n = 22), ovary (n = 18), and endometrium (n = 12), were either invariably negative with all five antibodies (endometrial adenocarcinoma, non-mucinous ovarian adenocarcinoma) or demonstrated selective and variable positivity (lung: D14, 50%; ovarian mucinous: D14, 50%). Among large polygonal cell carcinomas (hepatocellular carcinoma, renal cell carcinoma, melanoma, and adrenal carcinoma), only hepatomas stained positively, showing a distinctive canalicular staining pattern with the B18 (BGP epitope) (55%) and polyclonal antibody (50%). In the small polygonal cell carcinoma category, true CEA positivity was rare in breast (D14, 10% and B7.1, 14%) and never seen in prostatic carcinomas and carcinoid tumors. A subset of these breast (8 of 42), prostate (4 of 22), and carcinoids (4 of 7) showed exclusive positivity for the B18 antibody (NCA/BGP epitope). Ovarian serous papillary carcinomas (n = 14), papillary carcinomas of thyroid (n = 12), transitional cell carcinomas of the bladder (n = 11), and mesotheliomas (n = 3) were negative with all monoclonal antibodies. Metastatic carcinomas (n = 74) showed a similar pattern of reactivity to primary tumors. The authors conclude that CEA immunostaining may assist in identifying the histogenesis of epithelial tumors in several morphologic categories; that differential reactivities of the CEA monoclonal antibody panel exceed those of the polyclonal antibody; and that the discriminating power of the monoclonal panel is related to whether (1) CEA is or is not produced or (2) NCA or BGP is produced without concomitant CEA production. There is little evidence to support a concept of site-specific CEA species.     

Distribution of CA 125 in adenocarcinomas. An immunohistochemical study of 481 cases.

To determine the distribution of CA 125 in adenocarcinomas, formalin-fixed, paraffin-embedded tissue from 481 cases of adenocarcinoma from a variety of primary sites were studied using a monoclonal antibody to CA 125 (B27.1) and an avidin-biotin immunohistochemical technique. Positive reactivity was most common in adenocarcinomas of the endocervix, ovary, and endometrium (61% to 94%). However, relatively frequent positive reactions also were seen in adenocarcinomas of the pancreas (48%) and bile ducts (56%). Adenocarcinomas of the breast, lung, thyroid, distal esophagus/stomach, and liver (hepatocellular carcinoma) showed positive reactions in 7% to 20% of cases. Staining of rare tumor cells was seen in 2 of 45 colonic adenocarcinomas and in 1 of 61 prostatic adenocarcinomas. No reactivity was seen in the 54 renal cell carcinomas studied. Although CA 125 is most commonly present in gynecologic adenocarcinomas, it is also produced by some adenocarcinomas from many other sites. Immunostaining for CA 125 may be helpful in ruling out renal cell carcinoma in certain clinical settings.