Carcinoembryonic Antigen and Nonspecific Cross-reacting Antigen in Medullary Carcinoma of the Thyroid

Carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) were studied immunohisto-chemically in formalin fixed, paraffin embedded tissues of 73 cases of medullary carcinoma of the thyroid (MTC) using 2 polyclonal antibodies (CEA antisera cross-reactive with or without NCA), 3 monoclonal antibodies recognizing epitopes only on CEA, and one monoclonal antibody against NCA. The staining patterns of the 5 antibodies against CEA in MTCs were not different, and they reacted with 86.3% of all cases. With regard to the effects of fixatives on the staining patterns, samples fixed with formalin or 4% paraformaldehyde demonstrated CEA immunoreactivity in both the cell membrane and cytoplasm. In Bouin fixed tissue, the immunoreactivity was predominant on the cell membrane, whereas cytoplasmic positivity predominated in alcohol fixed specimens. Thus the difference in fixatives used in previous studies does not appear to be a major reason for the difference in the reported incidence of CEA positive MTCs. It is concluded that CEA is still a useful tumor marker for MTC and that it is detectable only in thyroid tumors originating from C cells, as seen in our series. The epitope defined by monoclonal antibody F106 88, present only on NCA, was found in 42.5% of all cases (49.2% of CEA positive MTCs). The NCA immunoreactivity was located in the tumor cell cytoplasm as globular aggregates, which were also labeled for CEA.     

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.     

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.     

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.     

Carcinoembryonic antigen in medullary thyroid carcinoma: an immunohistochemical study applying six novel monoclonal antibodies

Six novel mouse monoclonal antibodies raised against carcinoembryonic antigen (CEA) were used to study 22 medullary, ten papillary, ten follicular, and eight anaplastic thyroid carcinomas. The antibodies CEA 12-140-5, -7, and -10 reacted with the same epitope group (GOLD 4), whereas antibodies CEA 12-140-1, -2, and -4 recognized different epitopes (GOLD 5, 2 and 1, respectively) on the CEA molecule. All medullary carcinomas of the thyroid (MCTs) were stained when the antibodies CEA 12-140-5, -7, and -10 were applied, whereas CEA 12-140-1 stained all but five MCTs; CEA 12-140-2 and CEA-12-140 -4 each stained all but two. The CEA immunoreactivity was predominantly located diffusely in the cytoplasm but occasionally was also concentrated along the cell membrane. CEA immunoreactivity was also observed in normal C-cells and C-cell nodules. The follicular, papillary, and anaplastic carcinomas were all CEA-negative with the monoclonal antibodies applied in this study. The differences in staining pattern of MCTs found with the various antibodies may be explained as a lack of expression of some epitopes in some tumors, or they may be due to a varying degree of masking of the epitopes by the extensive glycosylation of CEA and CEA-like substances.     

CEA immunoreactivity in metastatic malignant melanoma.

Immunohistochemical techniques may aid in the diagnosis of poorly differentiated metastatic tumors. Anti-carcinoembryonic antigen (CEA) antibodies have been used in the identification of epithelial neoplasms. However, recent unpublished data report CEA reactivity in malignant melanoma and melanoma cell lines. We studied 28 cases of known metastatic malignant melanoma with an antibody panel for CEA (polyclonal and monoclonal), AE1:3, S-100, and HMB-45. Reactivity for CEA (polyclonal) was seen in 15 of 28 (53%) cases: nine exhibited strong diffuse positivity, five moderate focal positivity, and one globular cytoplasmic staining. Focal reactivity for cytokeratin (AE1:3) was seen in three of 28 cases. HMB-45 staining was present in 23 of 28 (82%, including strong positivity in the cytokeratin-reactive cases). Staining for S-100 protein was strong in all cases. No staining was seen for CEA (monoclonal). CEA immunoreactivity is seen in a significant number of metastatic malignant melanoma cases. This may be due to CEA expression by tumor cells, or crossreactivity of the polyclonal antibody with substances such as nonspecific crossreacting antigen (NCA) that share antigenic sites with CEA. These findings emphasize the need for care in interpreting immunohistochemical results. Immunohistochemical evaluation of CEA should not be made alone, but only as part of a diagnostic antibody panel.     

Galectin-3 and carcinoembryonic antigen expression in medullary thyroid carcinoma: possible relation to tumour progression

AIMS: Galectin-3 is a beta-galactoside binding protein involved in multiple biological processes through interactions with complementary glycoconjugates. We analysed the expression and coexpression of galectin-3 and carcinoembryonic antigen (CEA), one of the putative galectin-3 ligands, in medullary thyroid carcinoma (MTC). METHODS AND RESULTS: An immunohistochemical study using monoclonal antibodies was performed on paraffin sections of 20 cases of sporadic MTC comprising 10 cases without and 10 cases with lymph node metastases at the time of surgery. CEA expression was found in all tumours, distributed predominantly in the cytoplasm and occasionally at the cell surface. In the majority of cases (18/20) moderate to strong intensity of staining was found in most of the cells. Positive cytoplasmic staining for galectin-3 was found in 16/20 cases, but varied in intensity and distribution from weak/focal (7/16) to moderate (7/16) or strong (2/16). More intense staining for galectin-3 was mainly associated with MTC cases involving lymph node metastases. Eight out of these 10 cases showed moderate to strong galectin-3 expression concomitant with CEA expression throughout the tumour tissue. CONCLUSIONS: These findings suggest that galectin-3 might play a role in the pathobiology of MTC. Simultaneous expression of galectin-3 and CEA in the same tumour cells at an advanced stage of MTC indicates the possibility of their autocrine cooperation during tumour progression.     

Granular cell myoblastoma: an immunoperoxidase study using a variety of antisera to human carcinoembroyonic antigen

Immunoperoxidase staining using five antisera to human carcinoembryonic antigen (CEA), including a mouse monoclonal antibody, was performed to investigate the expression of CEA reactivity in ten cases of granular cell myoblastoma. The granular cells were negative with four of the antisera although control sections of CEA producing colon carcinoma were positive. The single positive antiserum gave intense granular cytoplasmic staining of all tumour cells in the ten specimens studied. This reactivity was abolished after absorption of the antiserum with a perchloric acid extract of human lung to remove cross-reacting antibodies against non-specific cross-reacting antigen (NCA); a procedure which did not affect the staining of colon carcinoma specimens. The results indicate that the granular cells do not contain CEA but express a related antigen and that care in the choice of primary antiserum is important if the immunocytochemical detection of this antigen is to be used as a diagnostic aid.     

A novel CEA-cross-reacting antigen of molecular weight 140,000 expressed on human lymphoid cell lines

To investigate the possible expression of the carcinoembryonic antigen (CEA) gene family products on lymphoid cells, we screened 28 human cell lines derived from malignant lymphoid cells for reactivity with monoclonal antibodies (MAbs) against CEA and nonspecific cross-reacting antigen (NCA), which is one of the CEA gene family members. Six cell lines (four B cell lines and two non-T, non-B cell lines) were found to react, by a membrane immunofluorescence test, with an MAb, F34-187, which recognizes an antigenic determinant shared between CEA and NCA. None of the 15T cell lines was reactive with any MAbs tested. A glycoprotein antigen isolated with F34-187 from the cell surface showed an apparent molecular mass of ca 140 and 70 kDa in the glycosylated and deglycosylated forms, respectively, and was unreactive with MAbs specific for CEA or NCA, suggesting that the antigen is a new member of the CEA gene family.     

Characterization of monoclonal antibodies to carcinoembryonic antigen with increased tumor specificity

Nine monoclonal antibodies reacting with carcinoembryonic antigen (CEA) were produced after immunization of mice with either purified CEA or a CEA-producing human cell line. Their specificities were assessed by immunohistochemistry on tissue sections of neoplastic and nonneoplastic lesions. These monoclonal antibodies have different patterns of tissue reactivity. Two of them, D14 and B18, were found to have a high degree of specificity for colonic carcinoma and did not react with formalin-fixed paraffin-embedded sections of normal colon with standardized staining conditions. Most cases of noncolonic adenocarcinomas and normal epithelial structures were not stained by these two monoclonal antibodies. The specificity of the monoclonal antibodies was further investigated immunochemically using intact, reduced, and alkylated or chemically fragmented CEA. Liquid phase radioimmunoassays and antibody competition immunoenzymatic assays confirmed that the antibodies recognize different epitopes of CEA. These data support the concept of CEA heterogeneity and the reactivity of the D14 and B18 monoclonal antibodies with colonic adenocarcinomas indicates that they are useful immunohistochemical probes.     

Immunohistochemical characterization of ovarian borderline tumors of intestinal and mullerian types.

A panel of monoclonal antibodies (MAbs) including MOv2, MOv8, anti-CA 19-9, and anti-carcinoembryonic antigen (CEA), and a polyclonal antibody against CEA, was applied to three types of ovarian borderline tumors. The tumors included 19 intestinal-type mucinous borderline tumors (IMBTs), 22 endocervical-like mucinous borderline tumors (EMBTs), and 23 mixed-epithelial borderline tumors (MEBTs); the latter two tumors are of mullerian type. Statistically significant differences in the percentage of positive IMBTs compared to the mullerian tumors were seen for anti-CEA and MOv8; strikingly different staining patterns were also seen. IMBTs were more often and more diffusely CEA-positive than were the mullerian tumors; within the mullerian tumors, only one type of cell, the indifferent eosinophilic cell, was consistently CEA positive. The MAbs MOv2, MOv8, and anti-CA 19-9 showed more extensive positivity in the mullerian tumors than in the IMBTs. This study highlights the differences in cell types between IMBTs and these two types of mullerian borderline tumors.     

Expression of ras oncogene p21 antigen in normal and proliferative thyroid tissues.

The ras oncogene p21 antigen (p21) has been identified in several epithelial malignancies, including breast, colon, bladder, and prostate. The pattern and intensity of immunoreactivity between normal and neoplastic tissues has been distinctly different. The authors examined thyroid lesions from 73 different cases by immunohistochemistry for the expression of p21 with a monoclonal antibody (RAP-5). Normal thyroid tissues (4) showed the least immunoreactivity, while papillary carcinomas (8), Hurthle cell carcinomas (10), and follicular carcinomas as (3) showed slightly more intense staining than Hurthle cell adenomas (12) or follicular adenomas (9). Anaplastic carcinomas (4) showed much less intense staining than most other carcinomas, while medullary thyroid carcinomas (5) showed only slight immunoreactivity. Inflammatory thyroid lesions associated with goiters, including Hashimoto's thyroiditis (6) and Graves' disease (8), showed moderate to intense expression of p21 as did multinodular goiters (4). Semiquantitative analysis of staining intensity by serial dilution of the primary antibody showed significant differences in staining between normal thyroid and some carcinomas (P less than 0.05), but not between carcinomas and adenomas. These results show that while antibody RAP-5 detects an antigen that is only weakly expressed in normal thyroids, this antigen is more strongly expressed in benign and malignant thyroid tumors, as well as in inflammatory and nonneoplastic proliferative thyroid lesions. It is thus not helpful in identifying differences between neoplastic and non-neoplastic thyroid lesions.     

Immunocytological staining reactions of anti-carcinoembryonic antigen, Ca, and anti-human milk fat globule monoclonal antibodies on benign and malignant exfoliated mesothelial cells.

A panel of three monoclonal antibodies were used in an immunoalkaline phosphatase staining method on a series of serous effusion samples from cases of mesothelioma, lung carcinoma, and benign disease. The antibodies used were anti-carcinoembryonic (CEA) antigen, Ca, and anti-human milk fat globule membrane antigen. Antibodies to the Ca antigen and human milk fat globule membrane antigen stained 75% and 83% of mesothelioma and 75% of cases of lung carcinoma, respectively. The anti-CEA antibody stained most cases of lung carcinoma strongly but was negative on 11 of 12 cases of mesothelioma and showed weak staining on one case. Benign cases were negative with all three antibodies. These three antibodies may be useful in distinguishing benign and malignant mesothelial cells and lung carcinoma in serous effusions.     

Induction of microsomal antigen and comparison with histologic localization of HLA-DR in Graves' thyroid tissue

We have characterized thyroid microsomal antigen (M-Ag) prepared from Graves' and normal thyroid tissues using 100,000 x g thyroid membrane fractions in enzyme-linked immunosorbent assays with pooled polyclonal human sera containing high titers of antibody to M-Ag. A ten-fold parallel increase in dose inhibition potencies occurred with M-Ag preparations from Graves' as compared to normal thyroid tissue. The M-Ag preparations were further evaluated by SDS-polyacrylamide gel electrophoresis and proteins visualized by Western blot using high titer microsomal antibody (M-Ab) sera (n = 2) devoid of thyroglobulin antibody activity. We found discrete 100 kD relative molecular mass bands in Graves' M-Ag preparations (n = 3) under nonreducing conditions which were only poorly resolved in normal thyroid M-Ag (n = 3) using up to 100 micrograms of protein per lane. The cellular localization of M-Ag was then investigated using the avidin-biotin-peroxidase technique on frozen sections of Graves' and normal human thyroid tissue with a murine monoclonal antibody reactive with human M-Ag and thyroid peroxidase. M-Ag reactivity was similar in both Graves' and normal thyroid tissues and localized to the entire follicular cell membrane with more intense staining occurring on the inner follicular cell membrane. This was in contrast to follicular cell staining for HLA-DR antigen which was present in 6 of 10 Graves' tissues examined and absent in normal thyroid tissue. Staining for HLA-DR antigen also occurred on the follicular cell surface membrane with occasional enhancement at the thyrocyte apical cell membrane. We conclude: a) M-Ag is induced approximately 10-fold in Graves' thyroid tissue and can be objectively quantified in ELISA systems, 2) There were no detectable qualitative differences between M-Ag from Graves' and normal thyroid tissue, and 3) HLA-DR antigen was detected on 60% Graves' tissues in a cell surface distribution similar to that observed for M-Ag in both Graves' and normal tissues.     

Differential expression of carcinoembryonic antigens and non cross-reacting antigens in the human thymus. Analysis on frozen sections and cultured epithelial cells using monoclonal antibodies

The organization of epithelial cells in distinct areas of the thymus appears important for understanding the pathways of T-cell differentiation. The presence of carcinoembryonic antigen (CEA) was investigated on sections of human thymus and in cultures of thymic epithelial cells through use of monoclonal antibodies (Mab) discriminating CEA and 2 non cross-reacting antigens (NCA 55 and NCA 95). All together, 5 monoclonal antibodies were used. The Mab 35 and 73 recognized exclusively a specific CEA antigenic determinant, whereas Mab 47, 192 and 202 were also reactive with CEA cross-reacting antigens. By immunofluorescence or the immunoperoxidase technique, staining of CEA was restricted essentially to Hassall's corpuscles and a few adjacent epithelial cells on thymic sections; this pattern was similar to distribution of Ca 19-9 antigen. Additionally, the 47, 192 and 202 antibodies were reactive with a keratin-negative subset mainly located in the cortex. Furthermore, a subset of keratin-positive cells bearing CEA molecules was observed in thymic epithelial cell cultures. Positive cells comprised less than 3% with Mab 35 and 73, and reached up to 12% with Mab 47, 192 and 202. By flow cytometry analysis, staining intensity varied with the epitope; it was much weaker with Mab 35, 47 and 73 than with Mab 192 and 202. The CEA content in culture supernatants was inversely correlated to the number of CEA positive cells. Thus, CEA could be considered as a marker of a late maturation stage of medullary epithelial cells culminating in Hassall's corpuscles and could contribute to delineating the heterogeneity of thymic epithelial cells.     

Mouse-human chimeric monoclonal antibody to carcinoembryonic antigen (CEA): in vitro and in vivo activities

Mouse-human chimeric antibody specific for human carcinoembryonic antigen (CEA) was produced by recombinant DNA techniques. The genes of the mouse variable regions of heavy and light chains were cloned from the mouse hybridoma, 2.7.1G.10., which secreted anti human CEA antibody (IgG1, kappa), and were joined with human gamma 1 and kappa constant genes. The affinity of the resultant chimeric antibody to its relevant antigen was the same as that of the parental mouse monoclonal antibody when analysed by Scatchard plot analysis. The chimeric antibody showed a potent antibody dependent cell-mediated cytotoxicity (ADCC) activity with human peripheral blood mononuclear cells against CEA-positive human adenocarcinoma cells. In vivo imaging analysis revealed that the present chimeric antibody was specifically localized on the tumor site. These results indicate that our mouse-human chimeric antibody is a promising reagent for the diagnosis and therapy of CEA-positive human cancers.     

Antigenic phenotype of malignant mesotheliomas and pulmonary adenocarcinomas. An immunohistologic analysis demonstrating the value of Leu M1 antigen.

To evaluate the usefulness of an immunohistologic approach to the differential diagnosis of mesothelioma and pulmonary adenocarcinoma, the authors studied paraffin-embedded, fixed tissue sections from 50 primary adenocarcinomas of the lung and 28 mesotheliomas of the pleura by using a panel of monoclonal antikeratin, antihuman milk fat globule (HMFG-2), anti-Leu M1, and monoclonal anticarcinoembryonic antigen (CEA) antibody; we also used a conventional heterologous anti-CEA antiserum with and without prior absorption with spleen powder to remove antibodies to nonspecific cross-reacting antigen (NCA). Keratin was present in both mesotheliomas and adenocarcinomas and did not help in distinguishing between these two neoplasms. HMFG-2 was detected in 48 (96%), and Leu M1 was positive in 47 (94%) of the adenocarcinomas, but not in any of the mesotheliomas. By using conventional rabbit antiserum, the authors detected CEA in the majority of adenocarcinomas (96%), but also in two cases of mesothelioma. When the anti-CEA antiserum was absorbed with NCA, the number of positively reacting adenocarcinomas decreased considerably to 76%; however, after this treatment, none of the mesotheliomas gave positive reactions. The monoclonal anti-CEA antibody was reactive in 36 of the adenocarcinomas (72%), but in none of the mesotheliomas. Our results indicate that, in addition to HMFG-2 and CEA, the expression of Leu M1 antigen by most primary pulmonary adenocarcinoma (94%) and its absence in mesothelioma could be used as a valuable marker for primary adenocarcinoma of the lung that involves the pleura and permits its differentiation from mesothelioma.     

Immunoscintigraphy

Immunoscintigraphic methods present a great step forward in non-invasive diagnostics. They contribute not only in tumor diagnostic where monoclonal antibodies against tumorous antigens (TAG 72, CEA) are used but also in the sphere of inflammation diagnostic with the use of monoclonal antibody BW 250/183 which is bound onto non-specific cross reacting antigen NCA 95 of granulocytes. Another sphere of interest is the detection of heart muscle damage with the use of monoclonal antibody against myosin and detection of venous thrombosis with the use of monoclonal antibody against fibrin. Monoclonal antibodies are labelled with indium 111 or technecium 99m.     

Comparison of immunoreactivity between two different monoclonal antibodies recognizing peptide and polysialic acid chain epitopes on the neural cell adhesion molecule in normal tissues and lung tumors.

A comparative immunohistochemical study of two different monoctonal antibodies against different epitopes on the neural cell adhesion molecule (N-CAM) was performed. Various normal tissues and lung tumors were examined for reactivity with NCC-LU-243, a monoclonal antibody which recognizes a peptide epitope on N-CAM, and monoclonal antibody 735 (MoAb 735), which reacts with a polysialic acid chain epitope on N-CAM. When acetone-fixed normal tissues were used, the immunoreactivities of MoAb 735 and NCC-LU-243 were not identical. In lung tumors, almost all small cell cancers (SCLC) and carcinoid tumors, and some non-SCLC were stained by both monoclonal antibodies. NCC-LU-243 stained the cell membrane only of almost all SCLC cells and clusters of non-SCLC cells. MoAb 735 stained the cell membrane of SCLC in a patchy manner and not only the cell membrane but also the cytoplasm of some non-SCLC. However cytoplasmic staining was evaluated as ‘not positive’. The number of positive cases and the size of the positive tumor cell population determined by cell membrane staining with MoAb 735 were smaller than those determined with NCC-LU-243 in both SCLC and non-SCLC cases. In routinely formalin-fixed materials, the immunoreactivity of both monoclonal antibodies, especially of NCC-LU-243, decreased after prolonged fixation as in surgically resected and autopsy materials. However, both monoclonal antibodies were found to be useful when materials were fixed for a short period of time as in biopsy specimens.