1159
alcohol may be caused by the generation of endogenous morphine-like alkaloids from the interaction of acetaldehyde and dopamine. Some support came from the work
of Cohen
and Collins8 who demonstrated the formation alkaloids from catecholamines and acetaldehyde such of in bovine adrenal tissue in vitro, but the theory has been strongly criticised by others, notably Seevers.9 Moreover, those accustomed to taking both opiates and alcohol have described the gross differences between their wrote "crude opium ... effects; Thomas de is incapable of producing any state of body at all resembling that which is produced by alcohol: and not in degree only incapable, but even in kind ... it differs
Quincey’O
altogether." However, the discovery of the endogenous opioid peptides has led to renewed speculation and it is possible that alcohol produces intoxication by causing release of such peptides. If this is true, and if the ability of naloxone to prevent, or reverse, the effects of greater degrees of intoxication is confirmed, the physiological and therapeutic, as well as the social and legal, implications are considerable. We thank Winthrop Ltd. and Tanqueray Gordon & Co. Ltd. for financial support. Requests for reprints should be addressed to W. J. J., City Hospital, Nottingham NG5 1PB. REFERENCES 1. Blum K, Futterman S, Wallace JE, Schwertner HA. Naloxone-induced inhibition of ethanol dependence in mice. Nature 1977; 265: 49-51. 2. Schenk GK, Engelmeier M-P, Matz D, Pach J. High dosage naloxone treatment in acute alcohol intoxication. Proc CINP Congress, Vienna 1978; 386. 3. Sorensen SC, Mattison KW. Naloxone as an antagonist in severe alcohol intoxication. Lancet 1978; ii: 688-89. 4. Mackenzie AI. Naloxone in alcohol intoxication. Lancet 1979; i: 733-34. 5. Wilkinson RT, Houghton D. Portable four-choice reaction time test with magnetic tape memory. Behav Res Methods Instr 1975; 7: 441-46. 6. Wilkinson R. Some factors influencing the effect of environmental stressors upon performance. Psychol Bull 1969; 72: 260-72. 7. Davis VE, Walsh MJ. Alcohol, amines, and alkaloids: a possible biochemical basis for alcohol addiction. Science, 1970; 167: 1005-07. 8. Cohen G, Collins M. Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism. Science 1970; 167: 1749-51. 9. Seevers MH. Morphine and ethanol physical dependence: a critique of a hypothesis. Science 1970; 170: 1113-14. 10. de Quincey T. Confessions of an English Opium Eater, London: Taylor and
Hessey, 1822.
"The likely outcome of the forthcoming Government consultative document on the future of the National Health Service will be structural change on such a scale as could endanger financial control in the Service, without providing the improvements in management or the savings so far claimed ... further structural change in the NHS—such as the abolition of the area tier which the Government is now advocating—will, as it did in the mid-1970s, divert management from its vital task of planning to meet future demands within finite resources. Equally seriously, financial control, which has been significantly improved since 1974, will undoubtedly be damaged if staff are expected to move to new posts and experienced officers forced into early retirement . . . Morale in the NHS, already lowered by a combination of uncertainty about the future of the Service and by the shortage of resources, could well sink still further. There is not the same enthusiasm and widespread acceptance of the need for change which welcomed the new management systems in 1974 ... Where change is required it should be made swiftly under schemes prepared by the present Regional Health Authorities ... it is vital that firm financial control should not be sacrificed for too dogmatic a concern for tidy structures."—Mr TREVOR RIPPINGTON, chairman, Association of Health Service Treasurers, at the Association’s annual conference on Nov. 8.
DISTINCTION BETWEEN ENDOCERVICAL AND ENDOMETRIAL ADENOCARCINOMA WITH IMMUNOPEROXIDASE STAINING OF CARCINOEMBRYONIC ANTIGEN IN ROUTINE HISTOLOGICAL TISSUE SPECIMENS TORSTEN WAHLSTRÖM MATTI KORHONEN
JAN LINDGREN MARKKU SEPPÄLÄ*
Departments of Pathology, Bacteriology and Immunology, and Obstetrics and Gynæcology, University of Helsinki, Finland The differential diagnosis of endocervical and endometrial adenocarcinomas can be improved by the demonstration of carcinoembryonic antigen (CEA) in tissue by means of immunoperoxidase staining. Tissue from 131 (80%) of 163 patients with endocervical adenocarcinoma but only 11 (8%) of 137 patients with endometrial adenocarcinoma was CEA-positive. The commonest exceptions were endocervical mesonephroid adenocarcinomas (which were CEA-negative) and endometrial adenosquamous carcinomas (which were CEA-positive). After exclusion of these on simple morphological criteria, 86 of 107 endocervical adenocarcinomas (80%) were CEA-positive, and all 122 endometrial adenocarcinomas were CEA-negative. The remarkable difference in the expression of CEA between endocervical and endometrial adenocarcinomas suggests a novel application of immunohistochemistry in routine clinical practice.
Summary
Introduction THE histological variability of endocervical and endometrial adenocarcinomas has created problems in their differential diagnosis, not least because specimens obtained by curettage of the endocervix may be contaminated with endometrial tissue.1,2 Attempts to improve this distinction have included studies on the cellular content of mucin3 and other mucosubstances,4 but they have not been applicable to clinical practice. We present here results which demonstrate that immunoperoxidase staining of carcinoembryonic antigen (CEA) can be valuable in the routine distinction between endocervical and endometrial adenocarcinomas.
Materials and Methods Tissue Specimens Formalin-fixed paraffin-embedded tissue blocks from 163 patients with endocervical adenocarcinomas (table i) and 137 patients with endometrial adenocarcinomas (table n) were
studied. All adenocarcinomas of the endometrium were obtained by hysterectomy, and only cases with no endocervical spread were included. Endometrial adenocarcinoma was highly differentiated in 61 cases, moderately differentiated in 47, and poorly differentiated in 19. 6 patients had adenosquamous carcinoma and 4 mesonephroid carcinoma.
Immunoperoxidase Staining
,
The characteristics of the antiserum and the three-layer immunoperoxidase technique have been described elsewhere.’ The antiserum stained neoplastic cells of human colorectal carcinoma, and this was abolished by absorption with purified "Present address: Department of Reproductive Physiology, St. Bartholomew’s Hospital, London EC1A 7BE.
1160
Immunoperoxidase staining of CEA in endocervical adenocarcinoma. (a) Hwmatoxylin and eosin staining; (b) staining with anti-CEA antiserum, showing apical localisation of CEA; stained with anti-CEA antiserum completely absorbed with purified CEA. TABLE I-TISSUE CEA IN ENDOCERVICAL ADENOCARCINOMA — —
and
(c) adjacent control section
cinoma were CEA-positive, and CEA was also observed in 5 well-differentiated adenocarcinomas in which keratinised metaplastic squamous cells took the stain, whereas the adenoid cells of the same tumours were
CEA-negative. Discussion
TABLE II-TISSUE CEA IN ENDOMETRIAL ADENOCARCINOMA
The differential diagnosis of endocervical and endometrial adenocarcinomas is essential because of differences in treatment. In this study 80% of endocervical adenocarcinomas were CEA-positive, compared with 8% of endometrial adenocarcinomas, and the difference was accentuated when adenocarcinomas with mesonephroid or squamous elements were excluded. Though the qualitative interpretation of immunoperoxidase slides is unambiguous when appropriate controls are included, the difference between positive and negative results must also be quantitative because the immunoperoxidase test can only detect CEA concentrations of 3-5 µg/g or higher in formalin-fixed specimens.6 Even so, the clear distinction between endocervical and endometrial adenocarcinomas is likely to be valuable in routine clinical practice.
apparent with formalin-fixed human buffy-coat cells or normal endocervical or endometrial tissue. Adjacent control sections of endocervical and endometrial adenocarcinomas were processed with anti-CEA antiserum absorbed with purified CEA, and in each experiment sections from colorectal carcinoma served as a positive control.
CEA. No
staining
was
Results Endocervical Adenocarcinoma CEA was identified in 131 of 163 (80%) endocervical adenocarcinomas. In some tumours only the apical border of the cytoplasm was stained (see figure); in others the cytoplasm below the nucleus or the whole cytoplasm was evenly stained. 32 endocervical adenocarcinomas were CEA-negative (table I): 11 of these were mesonephroid adenocarcinomas, but in 21 cases no unusual histological features were observed.
We thank Prof. Tim Chard for valuable suggestions about the manuscript and Ms Tuula Numminen for technical assistance. This study was supported by grant no. 1 R01 CA 23809-01 from the National Cancer Institute, D.H.E.W. (T.W.) and grants from the Research Council for Medical Sciences, Academy of Finland (M.S.) and the Emil Aaltonen Foundation (J.L.). M.S. is a recipient of a grant from the Medical Research Council through St. Bartholomew’s Hospital, London. Requests for reprints should be addressed to T.W., Department of Pathology, University of Helsinki, 00290 Helsinki 29, Finland. REFERENCES 1.
The pathology and treatment of adenocarcinof the cervix. Cancer 1951; 4: 1066-72. 2. Hepler TK, Dockerty MB, Randall LM. Primary adenocarcinoma of the cervix. Am J Obstet Gynecol 1952; 63: 800-08. 3. Davis JR, Moon LB. Increased incidence of adenocarcinoma of uterine cervix. Obstet Gynecol 1975; 45: 79-83. 4. Sorvari TE. A histochemical study of epithelial mucosubstances in endometrial and cervical adenocarcinomas. Acta path microbiol scand 1969;
Gusberg SB, Corscaden JA. oma
suppl. 207: 1-85. Lindgren J, Wahlström T, Seppälä M. Tissue CEA in premalignant epithelial lesions and epidermoid carcinoma of the uterine cervix: Prognostic significance. Int J Cancer 1979; 23: 448-53. 6. Goldenberg DM, Sharkey RM, Primus FJ. Carcinoembryonic antigen in histopathology: Immunoperoxidase staining of conventional tissue sections. J 5.
Endometrial Adenocarcinoma CEA was identified in 11 of 137 endometrial adenocarcinomas (8%). All 6 cases of adenosquamous car-
Nat Cancer Inst 1976; 57: 11-22.
alcohol may be caused by the generation of endogenous morphine-like alkaloids from the interaction of acetaldehyde and dopamine. Some support came from the work
of Cohen
and Collins8 who demonstrated the formation alkaloids from catecholamines and acetaldehyde such of in bovine adrenal tissue in vitro, but the theory has been strongly criticised by others, notably Seevers.9 Moreover, those accustomed to taking both opiates and alcohol have described the gross differences between their wrote "crude opium ... effects; Thomas de is incapable of producing any state of body at all resembling that which is produced by alcohol: and not in degree only incapable, but even in kind ... it differs
Quincey’O
altogether." However, the discovery of the endogenous opioid peptides has led to renewed speculation and it is possible that alcohol produces intoxication by causing release of such peptides. If this is true, and if the ability of naloxone to prevent, or reverse, the effects of greater degrees of intoxication is confirmed, the physiological and therapeutic, as well as the social and legal, implications are considerable. We thank Winthrop Ltd. and Tanqueray Gordon & Co. Ltd. for financial support. Requests for reprints should be addressed to W. J. J., City Hospital, Nottingham NG5 1PB. REFERENCES 1. Blum K, Futterman S, Wallace JE, Schwertner HA. Naloxone-induced inhibition of ethanol dependence in mice. Nature 1977; 265: 49-51. 2. Schenk GK, Engelmeier M-P, Matz D, Pach J. High dosage naloxone treatment in acute alcohol intoxication. Proc CINP Congress, Vienna 1978; 386. 3. Sorensen SC, Mattison KW. Naloxone as an antagonist in severe alcohol intoxication. Lancet 1978; ii: 688-89. 4. Mackenzie AI. Naloxone in alcohol intoxication. Lancet 1979; i: 733-34. 5. Wilkinson RT, Houghton D. Portable four-choice reaction time test with magnetic tape memory. Behav Res Methods Instr 1975; 7: 441-46. 6. Wilkinson R. Some factors influencing the effect of environmental stressors upon performance. Psychol Bull 1969; 72: 260-72. 7. Davis VE, Walsh MJ. Alcohol, amines, and alkaloids: a possible biochemical basis for alcohol addiction. Science, 1970; 167: 1005-07. 8. Cohen G, Collins M. Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism. Science 1970; 167: 1749-51. 9. Seevers MH. Morphine and ethanol physical dependence: a critique of a hypothesis. Science 1970; 170: 1113-14. 10. de Quincey T. Confessions of an English Opium Eater, London: Taylor and
Hessey, 1822.
"The likely outcome of the forthcoming Government consultative document on the future of the National Health Service will be structural change on such a scale as could endanger financial control in the Service, without providing the improvements in management or the savings so far claimed ... further structural change in the NHS—such as the abolition of the area tier which the Government is now advocating—will, as it did in the mid-1970s, divert management from its vital task of planning to meet future demands within finite resources. Equally seriously, financial control, which has been significantly improved since 1974, will undoubtedly be damaged if staff are expected to move to new posts and experienced officers forced into early retirement . . . Morale in the NHS, already lowered by a combination of uncertainty about the future of the Service and by the shortage of resources, could well sink still further. There is not the same enthusiasm and widespread acceptance of the need for change which welcomed the new management systems in 1974 ... Where change is required it should be made swiftly under schemes prepared by the present Regional Health Authorities ... it is vital that firm financial control should not be sacrificed for too dogmatic a concern for tidy structures."—Mr TREVOR RIPPINGTON, chairman, Association of Health Service Treasurers, at the Association’s annual conference on Nov. 8.
DISTINCTION BETWEEN ENDOCERVICAL AND ENDOMETRIAL ADENOCARCINOMA WITH IMMUNOPEROXIDASE STAINING OF CARCINOEMBRYONIC ANTIGEN IN ROUTINE HISTOLOGICAL TISSUE SPECIMENS TORSTEN WAHLSTRÖM MATTI KORHONEN
JAN LINDGREN MARKKU SEPPÄLÄ*
Departments of Pathology, Bacteriology and Immunology, and Obstetrics and Gynæcology, University of Helsinki, Finland The differential diagnosis of endocervical and endometrial adenocarcinomas can be improved by the demonstration of carcinoembryonic antigen (CEA) in tissue by means of immunoperoxidase staining. Tissue from 131 (80%) of 163 patients with endocervical adenocarcinoma but only 11 (8%) of 137 patients with endometrial adenocarcinoma was CEA-positive. The commonest exceptions were endocervical mesonephroid adenocarcinomas (which were CEA-negative) and endometrial adenosquamous carcinomas (which were CEA-positive). After exclusion of these on simple morphological criteria, 86 of 107 endocervical adenocarcinomas (80%) were CEA-positive, and all 122 endometrial adenocarcinomas were CEA-negative. The remarkable difference in the expression of CEA between endocervical and endometrial adenocarcinomas suggests a novel application of immunohistochemistry in routine clinical practice.
Summary
Introduction THE histological variability of endocervical and endometrial adenocarcinomas has created problems in their differential diagnosis, not least because specimens obtained by curettage of the endocervix may be contaminated with endometrial tissue.1,2 Attempts to improve this distinction have included studies on the cellular content of mucin3 and other mucosubstances,4 but they have not been applicable to clinical practice. We present here results which demonstrate that immunoperoxidase staining of carcinoembryonic antigen (CEA) can be valuable in the routine distinction between endocervical and endometrial adenocarcinomas.
Materials and Methods Tissue Specimens Formalin-fixed paraffin-embedded tissue blocks from 163 patients with endocervical adenocarcinomas (table i) and 137 patients with endometrial adenocarcinomas (table n) were
studied. All adenocarcinomas of the endometrium were obtained by hysterectomy, and only cases with no endocervical spread were included. Endometrial adenocarcinoma was highly differentiated in 61 cases, moderately differentiated in 47, and poorly differentiated in 19. 6 patients had adenosquamous carcinoma and 4 mesonephroid carcinoma.
Immunoperoxidase Staining
,
The characteristics of the antiserum and the three-layer immunoperoxidase technique have been described elsewhere.’ The antiserum stained neoplastic cells of human colorectal carcinoma, and this was abolished by absorption with purified "Present address: Department of Reproductive Physiology, St. Bartholomew’s Hospital, London EC1A 7BE.
1160
Immunoperoxidase staining of CEA in endocervical adenocarcinoma. (a) Hwmatoxylin and eosin staining; (b) staining with anti-CEA antiserum, showing apical localisation of CEA; stained with anti-CEA antiserum completely absorbed with purified CEA. TABLE I-TISSUE CEA IN ENDOCERVICAL ADENOCARCINOMA — —
and
(c) adjacent control section
cinoma were CEA-positive, and CEA was also observed in 5 well-differentiated adenocarcinomas in which keratinised metaplastic squamous cells took the stain, whereas the adenoid cells of the same tumours were
CEA-negative. Discussion
TABLE II-TISSUE CEA IN ENDOMETRIAL ADENOCARCINOMA
The differential diagnosis of endocervical and endometrial adenocarcinomas is essential because of differences in treatment. In this study 80% of endocervical adenocarcinomas were CEA-positive, compared with 8% of endometrial adenocarcinomas, and the difference was accentuated when adenocarcinomas with mesonephroid or squamous elements were excluded. Though the qualitative interpretation of immunoperoxidase slides is unambiguous when appropriate controls are included, the difference between positive and negative results must also be quantitative because the immunoperoxidase test can only detect CEA concentrations of 3-5 µg/g or higher in formalin-fixed specimens.6 Even so, the clear distinction between endocervical and endometrial adenocarcinomas is likely to be valuable in routine clinical practice.
apparent with formalin-fixed human buffy-coat cells or normal endocervical or endometrial tissue. Adjacent control sections of endocervical and endometrial adenocarcinomas were processed with anti-CEA antiserum absorbed with purified CEA, and in each experiment sections from colorectal carcinoma served as a positive control.
CEA. No
staining
was
Results Endocervical Adenocarcinoma CEA was identified in 131 of 163 (80%) endocervical adenocarcinomas. In some tumours only the apical border of the cytoplasm was stained (see figure); in others the cytoplasm below the nucleus or the whole cytoplasm was evenly stained. 32 endocervical adenocarcinomas were CEA-negative (table I): 11 of these were mesonephroid adenocarcinomas, but in 21 cases no unusual histological features were observed.
We thank Prof. Tim Chard for valuable suggestions about the manuscript and Ms Tuula Numminen for technical assistance. This study was supported by grant no. 1 R01 CA 23809-01 from the National Cancer Institute, D.H.E.W. (T.W.) and grants from the Research Council for Medical Sciences, Academy of Finland (M.S.) and the Emil Aaltonen Foundation (J.L.). M.S. is a recipient of a grant from the Medical Research Council through St. Bartholomew’s Hospital, London. Requests for reprints should be addressed to T.W., Department of Pathology, University of Helsinki, 00290 Helsinki 29, Finland. REFERENCES 1.
The pathology and treatment of adenocarcinof the cervix. Cancer 1951; 4: 1066-72. 2. Hepler TK, Dockerty MB, Randall LM. Primary adenocarcinoma of the cervix. Am J Obstet Gynecol 1952; 63: 800-08. 3. Davis JR, Moon LB. Increased incidence of adenocarcinoma of uterine cervix. Obstet Gynecol 1975; 45: 79-83. 4. Sorvari TE. A histochemical study of epithelial mucosubstances in endometrial and cervical adenocarcinomas. Acta path microbiol scand 1969;
Gusberg SB, Corscaden JA. oma
suppl. 207: 1-85. Lindgren J, Wahlström T, Seppälä M. Tissue CEA in premalignant epithelial lesions and epidermoid carcinoma of the uterine cervix: Prognostic significance. Int J Cancer 1979; 23: 448-53. 6. Goldenberg DM, Sharkey RM, Primus FJ. Carcinoembryonic antigen in histopathology: Immunoperoxidase staining of conventional tissue sections. J 5.
Endometrial Adenocarcinoma CEA was identified in 11 of 137 endometrial adenocarcinomas (8%). All 6 cases of adenosquamous car-
Nat Cancer Inst 1976; 57: 11-22.
