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Immunohistochemical localization of placental alkaline phosphatase, carcinoembryonic antigen, and cancer antigen 125 in normal and neoplastic human lung
35 categorised semiquantitatively into four proliferative grades, a classification that can be performed rapidly and reproducibly by the pathologist. In keeping with previous cell kinetic studies all small cell carcinomas had high proliferation rates, whereas the carcinoid tumours were in the lowest grade. In contrast, the adenocarcinomas (27 cases) and s~Lqmous cell carcinomas (63 cases) varied widely in their proliferative state, in keeping with their heterogeneous, morphological, and clinical behaviour. In~m/nocytochemical labelling of lung tumour biopsy specimens with antibody Ki67 is a s i d l e technique within the scope of routine surgical pathology laboratories, which might enable these tumours to be classified according to their proliferative status and treatment to be selected accordingly. Neuron-Specific Enolase (NSE) in Lung Cancer: An Immunohistochemical and Inn~unoenzymatic Study. Leonardo, E., Dogliotti, C., Oliaro, A. Cattedra di Tecnica e Diagn. Citopat., Dipartimento di Scienze Biomediche ed Oncologia Umana, Univ. Torino, Torino, Italy. Minerva Med. 77: 977-980, 1986. Serum level of neuro-specific enolase (NSE) was determined in 20 lung cancer patients. NSE concentration was detected also in neoplastic tissue and NSE-positive neoplastic cells on histological sections were observed immunohistochemically. The presence of a high level of NSE was showed in small cell lung cancer. Somatostatin and Adrenocorticotrophic Hormone Like Immunoreactivity in Small Cell Carcinoma of the Lung. Chretien, M.F., Pouplard-Barthelaix, A., Dubois, M.P. et al. Laboratoire d'Histologie-Embryologie-Cytologie, Centre Hospitalier Universitaire, 49045-Angers Cedex, France. J. Clin. Pathol. 39: 418-422, 1986. The inmmnocytological detection of adrenocorticotrophic hormone (ACT}{) and somatostatin release inhibitor factor (SRIF) like inmnlnoreactivity was carried out on tumour cells from bronchial brush smears in 39 cases of lung tumors. Results obtained were compared with the cytological and histological diagnosis and confirmed the high incidence of ACTH synthesis by malignant bronchial carcinoma cells: the same
phenomenon also seems to occur for somatostatin. The concomitant detection of ACTH and SRIF like immunoreactivity seems to be highly suggestive of small cell carcionma and indicates that the inmnmocytological detection of hormones carried out at the same time as cytological examination can improve the accuracy of the diagnosis. Expression of Vimentin in Surgically Resected Adenocarcinomas and Large Cell Carcinomas of the Lung. Upton, M.P., Hirohashi, S., Tome, Y. et al. Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan. Am. J. Surg. Pathol. I0: 560-567, 1986. The expression of vimentin in pulmonary carcinomas was studied in 285 cases of surgically resected lung cancer from our hospital files. Formalin fixed, paraffin-embedded sections were studied by inm~anoreactive staining techniques using two monoclonal antibodies against vimentin. Cases demonstrating vimentin positivity by the avidinbiotin-peroxidase method included ii of 129 adenocarcinomas studied (8.5%), and 15 of 61 large cell carcinomas studied (24.6%). Vimentin expression was not seen in any of the 51 squamous cell carcinomas or 35 small cell carcinomas in our series. The positive cases of adenocarcinoma were in moderately and poorly differentiated cancers. Four of the eight giant cell carcinomas (50%) demonstrated vimentin expression. All cases that exhibited vimentin positivity were studied for cytokeratin expression. Coexpression of vimentin and cytokeratin was demonstrated not only within the same tumor but also within the same cells in some cases stained by double antibody technique, including both adenocarcinomas and large cell carcinomas. Similar i~inunoreactive methods were also applied to sections from h,-,an lung cancer transplants grown in the nude mouse. Of 28 tumours studied, four of ii adenocarcinomas (36%) and all 4 large cell carcinomas demonstrated coexpression of vimentin and cytokeratin, while none of the five squamous cell carcinomas or eight small cell carcinomas expressed vimentin. Immunohistochemical Localization of Placental Alkaline Phosphatase, Carcinoembryonic Antigen, and Cancer Antigen 125 in Normal and Neoplastic H,-,anLung. Nouwen, E.J., Poller, D.E., Eerdekens, M.W.
36 et al. Department of Nephrology and Hypertension, University Hospital, B-2520 Edegem, Belgium. Camcer Res. 46: 866-876, 1986. Human placental alkaline phosphatase (HPLAP), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA 125) were localized i,m~nohistochemically in paraffin sections of normal lung tissue from 16 patients, using monoclonal antibodies and an indirect avidin-biotin-peroxidase staining procedure. HPLAP and CEA were present in epithelial cells of respiratory bronchioli and alveolar type I pneumocytes. CEA was also observed in the tracheal, bronchial, and bronchiolar epithelium. CA 125 was present in the tracheal, bronchial, bronchiolar, and terminal bronchiolar epithelium; in the tracheal and bronchial glands; and in the pleural mesothelium. Normal and hyperplastic type II pneumocytes were negative for HPLAP, CFA, and CA 125 but were histochemically positive for nonspecific alkaline phosphatase. Fetal lung tissue between ii and 15 weeks of gestation was negative for HPLAP, CEA, and CA 125. The fetal tracheal and bronchial epithelium, tracheal glands, and pleural mesothelium were positive for CA 125. For ten malignant pulmonary tumors investigated, HPLAP staining was observed in five, CEA in nine, and CA 125 in seven. The localization of HPLAP, CEA, and CA 125 in apparently normal constituents of all pulmonary specimens is in disagreement with the concept that the expression of these substances in the lung is indicative of abnormal cellular activity. The Diagnostic Distinction Between Malignant Mesothelioma of the Pleura and Adenocarcinoma of the Lung as Defined by a Monoclonal Antibody (B72.3). Szpak, C.A., Johnston, W.W., Roggli, V. et al. Department of Pathology, Duke University Medical Center, Durham, NC 27710, U.S.A. ~ . J. Pathol. 122: 252-260, 1986. The correct distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung has become increasingly complex, with a variety of histochemical, im~/nohistochemical, and ultrastructural studies to be performed on biopsy material. The reliability of immunohistochemical studies has been hampered by the use of polyclonal antisera to 'carcinoembryonic antigen (CEA)' and keratin. Hybridoma technology now offers monoclonal antibodies (MAbs) in unlimited
quantity and standardized quality to selective ranges of specific antigenic determinants. MAb B72.3, generated against a membrane-enriched fraction of ~,,an metastatic breast carcinoma, was used to distinguish malignant mesothelioma of the pleura from adenocarcinoma of the lung in tissue sections and was compared in terms of diagnostic utility with polyclonal anti-keratin and anti-CEA to make the same distinction. Reactivity with MAb B72.3 in at least 10% of tumor cells or more was noted in 19 of 22 adenocarcinomas of the lung (P>O.O001), whereas none of the 20 cases of malignant mesothelioma demonstrated comparable reactivity. Furthermore, MAb B72.3 showed no reactivity with benign mesothelial proliferations. MAb B72.3 thus appears to be an appropriate diagnostic adjunct capable of discriminating between these malignancies. Antigenic Phenotype of Malignamt Mesothelio,~s and Pulmonary Adenocarcinomas. An Immunohistologic Analysis Demonstrating the Value of Leu MI Antigen. Sheibani, K., Battifora, H., Burke, J.S. Division of Anatomic Pathology, City of Hope National Medical Center, Duarte, CA 91010, U.S.A. Am. J. Pathol. 123: 212-219, 1986. To evaluate the usefulness of an immunohistologic approach to the differential diagnosis of mesothelioma and pulmonary adenocarcinoma, the authors studies 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 MI, 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 crossreacting 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 2 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
phenomenon also seems to occur for somatostatin. The concomitant detection of ACTH and SRIF like immunoreactivity seems to be highly suggestive of small cell carcionma and indicates that the inmnmocytological detection of hormones carried out at the same time as cytological examination can improve the accuracy of the diagnosis. Expression of Vimentin in Surgically Resected Adenocarcinomas and Large Cell Carcinomas of the Lung. Upton, M.P., Hirohashi, S., Tome, Y. et al. Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan. Am. J. Surg. Pathol. I0: 560-567, 1986. The expression of vimentin in pulmonary carcinomas was studied in 285 cases of surgically resected lung cancer from our hospital files. Formalin fixed, paraffin-embedded sections were studied by inm~anoreactive staining techniques using two monoclonal antibodies against vimentin. Cases demonstrating vimentin positivity by the avidinbiotin-peroxidase method included ii of 129 adenocarcinomas studied (8.5%), and 15 of 61 large cell carcinomas studied (24.6%). Vimentin expression was not seen in any of the 51 squamous cell carcinomas or 35 small cell carcinomas in our series. The positive cases of adenocarcinoma were in moderately and poorly differentiated cancers. Four of the eight giant cell carcinomas (50%) demonstrated vimentin expression. All cases that exhibited vimentin positivity were studied for cytokeratin expression. Coexpression of vimentin and cytokeratin was demonstrated not only within the same tumor but also within the same cells in some cases stained by double antibody technique, including both adenocarcinomas and large cell carcinomas. Similar i~inunoreactive methods were also applied to sections from h,-,an lung cancer transplants grown in the nude mouse. Of 28 tumours studied, four of ii adenocarcinomas (36%) and all 4 large cell carcinomas demonstrated coexpression of vimentin and cytokeratin, while none of the five squamous cell carcinomas or eight small cell carcinomas expressed vimentin. Immunohistochemical Localization of Placental Alkaline Phosphatase, Carcinoembryonic Antigen, and Cancer Antigen 125 in Normal and Neoplastic H,-,anLung. Nouwen, E.J., Poller, D.E., Eerdekens, M.W.
36 et al. Department of Nephrology and Hypertension, University Hospital, B-2520 Edegem, Belgium. Camcer Res. 46: 866-876, 1986. Human placental alkaline phosphatase (HPLAP), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA 125) were localized i,m~nohistochemically in paraffin sections of normal lung tissue from 16 patients, using monoclonal antibodies and an indirect avidin-biotin-peroxidase staining procedure. HPLAP and CEA were present in epithelial cells of respiratory bronchioli and alveolar type I pneumocytes. CEA was also observed in the tracheal, bronchial, and bronchiolar epithelium. CA 125 was present in the tracheal, bronchial, bronchiolar, and terminal bronchiolar epithelium; in the tracheal and bronchial glands; and in the pleural mesothelium. Normal and hyperplastic type II pneumocytes were negative for HPLAP, CFA, and CA 125 but were histochemically positive for nonspecific alkaline phosphatase. Fetal lung tissue between ii and 15 weeks of gestation was negative for HPLAP, CEA, and CA 125. The fetal tracheal and bronchial epithelium, tracheal glands, and pleural mesothelium were positive for CA 125. For ten malignant pulmonary tumors investigated, HPLAP staining was observed in five, CEA in nine, and CA 125 in seven. The localization of HPLAP, CEA, and CA 125 in apparently normal constituents of all pulmonary specimens is in disagreement with the concept that the expression of these substances in the lung is indicative of abnormal cellular activity. The Diagnostic Distinction Between Malignant Mesothelioma of the Pleura and Adenocarcinoma of the Lung as Defined by a Monoclonal Antibody (B72.3). Szpak, C.A., Johnston, W.W., Roggli, V. et al. Department of Pathology, Duke University Medical Center, Durham, NC 27710, U.S.A. ~ . J. Pathol. 122: 252-260, 1986. The correct distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung has become increasingly complex, with a variety of histochemical, im~/nohistochemical, and ultrastructural studies to be performed on biopsy material. The reliability of immunohistochemical studies has been hampered by the use of polyclonal antisera to 'carcinoembryonic antigen (CEA)' and keratin. Hybridoma technology now offers monoclonal antibodies (MAbs) in unlimited
quantity and standardized quality to selective ranges of specific antigenic determinants. MAb B72.3, generated against a membrane-enriched fraction of ~,,an metastatic breast carcinoma, was used to distinguish malignant mesothelioma of the pleura from adenocarcinoma of the lung in tissue sections and was compared in terms of diagnostic utility with polyclonal anti-keratin and anti-CEA to make the same distinction. Reactivity with MAb B72.3 in at least 10% of tumor cells or more was noted in 19 of 22 adenocarcinomas of the lung (P>O.O001), whereas none of the 20 cases of malignant mesothelioma demonstrated comparable reactivity. Furthermore, MAb B72.3 showed no reactivity with benign mesothelial proliferations. MAb B72.3 thus appears to be an appropriate diagnostic adjunct capable of discriminating between these malignancies. Antigenic Phenotype of Malignamt Mesothelio,~s and Pulmonary Adenocarcinomas. An Immunohistologic Analysis Demonstrating the Value of Leu MI Antigen. Sheibani, K., Battifora, H., Burke, J.S. Division of Anatomic Pathology, City of Hope National Medical Center, Duarte, CA 91010, U.S.A. Am. J. Pathol. 123: 212-219, 1986. To evaluate the usefulness of an immunohistologic approach to the differential diagnosis of mesothelioma and pulmonary adenocarcinoma, the authors studies 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 MI, 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 crossreacting 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 2 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