ISSN: 0284-186X (Print) 1651-226X (Online) Journal homepage: http://www.tandfonline.com/loi/ionc20
Carcinoembryonic Antigen in Anal Carcinoma Gunnar Tanum, Anna E. Stenwig, Ole P. Børmer & Kjell M. Tveit To cite this article: Gunnar Tanum, Anna E. Stenwig, Ole P. Børmer & Kjell M. Tveit (1992) Carcinoembryonic Antigen in Anal Carcinoma, Acta Oncologica, 31:3, 333-335, DOI: 10.3109/02841869209108181 To link to this article: http://dx.doi.org/10.3109/02841869209108181
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 262
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ionc20 Download by: [220.127.116.11]
Date: 30 May 2016, At: 12:16
Acra Oncologica Vol. 31, No. 3, pp. 333-335, 1992
CARCINOEMBRYONIC ANTIGEN IN ANAL CARCINOMA
Downloaded by [18.104.22.168] at 12:16 30 May 2016
GUNNARTANUM, ANNAE. STENWIG, OLE P. B0RMER and KJELLM. TVEIT
Patients with squamous cell carcinoma of the anal canal occasionally present with an elevated level of carcinoembryonic antigen (CEA) in serum. The present study was performed to evaluate the clinical importanceof this observation.Serum CEA was measured in 106 patientsprior to chemo- and radiotherapy and during follow-up. Twenty patients had elevated serum CEA level before treatment. In 6 of 12 cases, serum CEA did not normalize after successful treatment and in 4 of 7 cases it rose no further despite progressive disease. CEA-positive tumours were more often poorly differentiated than CEA-negative tumours. There was no significant correlation between serum CEA, tumour CEA and prognosis. We conclude that measurement of serum CEA and staining of tumour CEA lack clinical importance.
Carcinoembryonic antigen (CEA) was identified more than 25 years ago (1). The antigen is expressed on the tumour cell surface and is also located in the cytoplasm. It is excreted from the cells of colorectal adenocarcinomas (2-5). The serum level is generally correlated to the tumour burden. About 80% of the patients with adenocarcinoma in colon and rectum have elevated serum CEA, while patients with carcinomas located elsewhere most often have normal values. Small amounts of CEA is present in normal tissue, and several benign diseases induce slightly elevated levels of serum CEA (6-8). Thus, CEA is not specific for certain malignant tumours. The clinical usefulness of serum CEA is mainly limited to patients with colorectal carcinoma. If serum CEA is elevated before treatment, the value falls to normal within one month following successful therapy. For these patients CEA is important for detection of recurrence at an early stage (9- 15). Patients with squamous cell carcinoma of the anal canal sometimes have elevated serum CEA level. The present study was performed to evaluate if measurement of serum CEA and staining of tumour CEA would add any information of clinical significance.
Submitted 5 July 1991. Accepted I I October 1991. Correspondence to: Dr Gunnar Tanum. The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. Address. As above (all authors).
Material and Methods A total of 106 patients received combined chemotherapy and radiotherapy for squamous cell carcinoma, including basaloid carcinomas (16), of the anal canal at the Norwegian Radium Hospital during 1983-1989. The series included 22 men and 84 women, mean age was 65.2 years (range 35-91). The patients received radiotherapy with a daily tumour dose of 2 Gy up to a total dose of 50 Gy given by 2 AP-PA opposed fields which covered the pelvis from perineum to the upper part of sacrum. Chemotherapy consisted of mitomycin C 10- 15 mg given as bolus on day 1 of radiotherapy and 5-Fu 1 000 mg/m2/day given as continuous infusions on days 1-4. The patients were examined one month and 3 months after treatment, then every 3 months for 2 years and every 6 months for 3 more years. Fifty-nine patients were observed for more than 3 years after treatment (end of 1990). Serum CEA was examined before treatment and at every follow-up visit. Until April 1988, serum CEA was measured by a direct radioimmunoassay using polyclonal CEA antibodies ( 17). while after that time an immunoradiometric assay using monoclonal CEA antibodies was employed (18). The reference limits of the assays were 150 IU/l and 5 pg/l respectively, as defined by the 97.5th percentile of population of blood donors and patients with non-malignant diseases ( 17, 18). Biopsy was taken from the primary tumour in all patients with elevated serum CEA ( n =20), fixed in buffered formalin and tumour blocks processed to paraffin. 333
Downloaded by [22.214.171.124] at 12:16 30 May 2016
G. TANUM ET AL.
Five pm sections were stained with hematoxylin and eosin and with a polyclonal CEA (Dako Corp., DK-2600 Glostrup, Denmark). The latter was absorbed with powder from spleen tissue prior to incubation to eliminatelreduce non-specific staining and was localized by an indirect peroxidase procedure. Sections were also stained with alcian green to exclude components of adenocarcinoma. A corresponding number (20 cases) of biopsies from patients with normal serum CEA-level underwent the same procedure. The latter were drawn at random from all patients with normal serum CEA. All sections were examined by one pathologist. Tumours were defined as CEA positive when more than 50% of the cells stained CEA positive. In these cases both cell membrane and cytoplasm showed a dark brown colour. Tumour differentiation was estimated according to generally accepted criteria ( 19), and evaluation was performed without knowing if the tumour was CEApositive or negative. Fisher's exact test was used for statistical calculations. Results None of the biopsies contained adenosquamous carcinoma or adenocarcinoma. Twenty patients presented with increased serum CEA level before treatment, median 352IU/l (range 167-1 728) and 8.5pg/l (range 5.2-28) respectively. Eighty-six patients had normal values ( < 150 IU/l or < 5 pg/l respectively). CEA-positive tumours were more often poorly differentiated than CEAnegative tumours (p < 0.01) but not significantly associated with prognosis (Table 1). Patients with increased serum CEA level (20 cases). One patient died of a heart-attack during treatment. Twelve
patients had a long-term complete response following treatment. Of these, serum CEA normalized within one month after treatment in 6 cases, while serum CEA persisted high in the other 6 cases. Seven patients had progressive disease after treatment. In 4 of these cases the serum CEA increased, while it in 3 cases remained stable. The primary tumour stained CEA-positive in 3 cases and CEA-negative in 17 cases. Elevated serum CEA was not significantly associated with prognosis (Table 2). Patients with normal serum C E A level (20 cases). Four patients had CEA-positive tumours, while 16 tumours were CEA-negative. Three CEA-positive tumours were poorly differentiated and one moderately differentiated. One patient with a poorly differentiated, CEA-positive tumour later developed extremely high levels of serum CEA parallel to growth of distant metastases.
Discussion Patients with squamous cell carcinoma of the anal canal occasionally present with increased serum CEA level. However, there are few, if any, reports about the clinical importance of this observation. The present study was therefore performed to evaluate if measurement of serum CEA and staining of tumour CEA should be included as routine procedures for these patients. In the present study 1/5 of the patients presented with increased serum CEA level. In half of these cases, serum CEA did not normalize during long-term complete response. One reason for this may be that irradiated tissue excrete CEA and hence keep serum CEA high. It is well known that increasing age and smoking may induce a slight increase of serum CEA. However, we found no such correlation that could explain
Table 1 Serum CEA, turnour CEA, and histopathological turnour direrentiation in patients with anal carcinoma Serum CEA level
No. pat. 4
Well Moderate Poor
0 0 3
Moderate Poor Increased
Moderate Poor * Twenty patients drawn by random from the 86 patients in the study population.
1 13 3
CEA IN ANAL CARCINOMA
Serum CEA, tumour CEA, and prognosis in patients with anal carcinoma
1. Gold P, Freedman DS. Specific carcinoembryonic antigens of the human digestive system. J Exp Med 1965; 12: 468-81. 2. Thomson DMP, Krupey J, Freedman DS. The radioim-
Number of patients Total
I 92 20
’ No evident disease at follow up.
Downloaded by [126.96.36.199] at 12:16 30 May 2016
One patient died of intercurrent disease.
the present observations. It is concluded that serum CEA is not a reliable indicator of treatment success in cases of anal carcinoma. Seven patients with high serum CEA before treatment later developed progressive disease. Of these, only 4 had increasing serum CEA. This indicates that serum CEA is of limited value in follow-up, even for patients with increased serum CEA prior to treatment. One patient who initially presented with normal serum CEA, later on developed distant metastases and extremely high levels of serum CEA. Unfortunately, no biopsies were taken from the metastases. One can therefore only speculate that the metastases strongly differed from the primary tumour concerning CEA production. One would expect a positive correlation between serum CEA and tumour CEA, but this was not the case. About 1/6 of the tumours stained CEA-positive, but this was independent of serum CEA level (Table 1). Apparently, the amount of CEA in the tumour cells did not correlate to their CEA secretion. There was a non-significant tendency towards a poorer prognosis in patients with both increased serum CEA and CEA positive tumours (Table 2). CEApositive tumours, however, were more often poorer differentiated than the CEA-negative tumours (Table 1). The importance of this finding remains uncertain, but it is possible that tumour CEA reflects histopathological differentiation and thereby correlates to prognosis. However, it must be concluded from the present study that measurement of serum CEA and staining of tumour CEA do not add information of clinical importance. At present, therefore, these tests have no place in the routine examination of patients with anal carcinoma.
munoassay of circulating carcinoembryonic antigen of the human digestive system. Proc Nat Acad Sci USA 1969; 64: 161-7. 3. Keep PA, h a k e BA, Rogers GT. Extraction of CEA from tumour tissue, fetal colon and patients’ sera and the effect of perchloric acid. Br J Cancer 1978; 37: 171-82. 4. G o s h RH, OBrien MJ, Steele G. Correlation of plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer. Am J Med 1981; 71: 246-53. 5 . Zamcheck N. The expanding field of colorectal cancer markers: CEA the prototype. Cancer Bull 1981; 33: 141-51. 6. Loewenstein MS, Zamcheck N. Carcinoembryonic antigen (CEA) levels in benign gastrointestinal disease states. Cancer 1978; 42: 1412-8. 7. Stevens DP, Mackay IR. Carcinoembryonic antigen raised in heavy cigarette smokers. Lancet 1973; 2: 1238-9. 8. Begent RHJ. The value of carcinoembryonic antigen measurement in clinical practice. Ann Clin Biochem 1984; 21: 231 -8. 9. Wanebo HJ, Stearns M, Schwartz MK. Use of CEA as a guide to second look procedure in patients with colorectal cancer. Ann Surg 1978; 188: 491-3. 10. Staab HJ, Anderer FA, Stumpf E, Hoornung A, Fischer R, Kieninger C. Evaluation of 84 second-look operations based on sequential CEA determinations together with clinical investigations in patients with recurrent gastrointestinal cancer. Am J Surg 1985; 149: 198-204. 11. Doos WG, Wolff WI, Shinva H, et al. CEA levels in patients with colorectal carcinoma and polyps. Cancer 1975; 366: 1996-2003. 12. Ziegenbein R, Jacobash KH, Pilgram G. Determination of CEA in plasma of patients with colorectal carcinoma and polyps. Arch Geschw 1980; 50: 165-8. 13. August DA, Ottow RT, Sugarbaker PH. Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev 1984; 3: 303-24. 14. Minton JP, Hoehn J, Gerber D, et al. Result of a 400-patient carcinoembryonic antigen second-look colorectal cancer study. Cancer 1985; 55: 1284-90. 15. Sugarbaker PM, Bloomer WD, Corbett ED. Carcinoembryonic antigen (CEA) monitoring of radiation therapy for colorectal cancer. AJR, Rad Ther Nucl Med 1976; 127: 641-4. 16. Dougherty BG, Evans HJ. Carcinoma of the anal canal: A study of 79 cases. J Clin Pathol 1985; 83: 159-64. 17. B ~ r m e r0. A direct assay for carcinoembryonic antigen in serum and its diagnostic value in metastatic breast cancer. Clin Biochem 1982; 15: 128-32. 18. Banner 0, Nustad K. Selection of monoclonal antibodies for use in an immunometric assay for carcinoembryonic antigen. J Immunol Methods 1990; 127: 171-8. 19. Morson BC, Dawson IM, Day DW, Jass JR, Price AB, Williams GT. Morson & Dawson’s gastrointestinal pathology. Oxford: Blackwell, 1990: 675-7.