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112 cases, of varying ages, which were diagnosed as having carcinoma of the bladder by cystoscopy and biopsy from the tumor, were investigated for the presence of alphafetoprotein (AFP) in the sera. 59 (52.6 %) out of the total, showed positive results, and no false positive results occured. Radioimmunoassay was capable of increasing the positivity rate still further. All of the cases were proved by liver scan and laparotomy to be free of metastasis, but all had bilharziasis during childhood, in which there is no factor affecting the liver that is responsible for the release of AFP, as the only species of bilharziasis present in Iraq is that of hematobium. Request reprints from: E. A. K. Alsabti, MB Ch BS, Albaath Protein Reference Unit Karadt Marium 500C2/1, Baghdad (IRAQ) Introduction Alphaphetoprotein (AFP) is a normal constituent of fetal serum [Gitlin], but the levels are low at birth and subsequently fall rapidly. The conditions in which elevated AFP in the sera were found, were embryonic tumors of the ovary and testis, primary hepatoma [Abeley], secondary deposits in the liver, hepatitis, cirrhosis, biliary atresia and others. Bladder carcinoma in Iraq is the first common tumor affecting males [Alsaleem]. The disease in more than 3A of the total number of cases is due to previous infestation with bilharziasis [Alsaleem] which is due to hematobium species. Thus the disease is much more common in the middle and lower parts of the country than in the northern part. The present report is concerned with findings in 112 cases with bladder carcinoma that had been studied by extensive clinical, histological, and biochemical investigations including AFP test. Materials and Methods Sera were made available from different hospitals in the country. They all had hematuria and loss of weight without any other genitourinary or general symptoms of the disease. Counter current electrophoresis as had been described by Kohn was used for the detection and identification of AFP in the sera, which was performed on cellulose acetate (CAM) supplied by Shandon (England). The pattern of depressions were described also by Kohn. A series of experiments with standard from various commercial sources, indicated a sensitivity of 220–1000 ng/ml or even higher. Using AFP control provided by Dakopatts, the presence of 220 ng/ml could still be clearly demonstrated. The positive control sera were calibrated and checked against standard sera and pure AFP from Behring. Liver function tests (on all cases), liver scan (on another ten cases), and laparotomy (on 49 cases) were done in the positive AFP cases to exclude any liver secondaries which many may regard as being responsible for AFP production. Results D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /1 8/ 20 17 8 :3 5: 53 P M AFP was detected in 59 (35 males, 24 female) out of the total 112 cases (52.6%). Their ages were ranging between 48–69 years (table J). Histopathological examinations of liver specimens obtained at laparatomy (in 49 cases out of the total 59 positive AFP cases in the series) showed no liver secondaries. In the remaining ten cases liver scan was normal. In all the cases liver function tests were normal. All the 59 positive AFP cases had previous childhood history of infestation with bilharziasis. At laparatomy, the tumor was found resectable in 41 cases and unresectable in the remaining eight cases referred for surgery. Biopsy from the bladder obtained by cystoscopy in the 59 cases showed 51 cases with squamous cell carcinoma and eight with transitional cell carcinoma. Table I. Clinic and histopathology of 59 bladder carcinoma positive AFP cases. Sex incidence Age (years) Complaint Duration of symptoms male 35 female 24 40–49: 3 cases 50–59: 22 cases Hematuria and loss of weight in all 59 cases1 year, 7 cases 2 year, 21 cases 60 + , 34 cases 2+ year, 31 cases Childhood history of bilharziasis in all cases 59 was presentHepatomegaly nil in all 5 9 cases Liver function were normal in all 59 cases Histopathology of bladder biopsy from cystoscopy Operability squamous cell carcinoma, 51 cases inoperable, 10 cases transitional cell carcinoma, 8 cases resectable, 41 cases unresectable, 8 cases Alsabti: Serum Alphafetoprotein in Bladder Carcinoma Discussion The hypothesis regarding the role of AFP in fetal development [Smith], its presence in normal human sera [Ruoslahti et ai] and possible reason for its corresponding reappearance in abnormal amounts in malignant hepatoma, teratocarcinoma [Smith], carcinoma of stomach [Alpert et ai], and other conditions has been extensively reviewed. The previous study in Iraq [Alsabti], showed positive AFP in 141 cases with bilharziasis diagnosed clinically and by intradermal tests and ova in mid stream urine samples, without any liver involvement that had been excluded by liver scan in all cases. Thus, in this study, a correlation was made between AFP and bilharziasis, infestation of which was present in all case histories. The most important point which must be raised in this study, is the failure of the test as a screening method, not only in our country, but in all other endemic areas of bilharziasis in the world. We made an effort to explain these results by assuming that bilharziasis may cause secondary liver fibrosis which may also be responsible for AFP production. Thus, we studied the gammaglobulin level in the sera, which increased in only eleven cases, and the presence of autoantibodies to liver homogenate in only three cases, out of a total of 59 cases. Unfortunately, this supposition was proved by the following factors to be untrue: Studies in Iraq [Shamma] showed that liver fibrosis needs longer time, which did not correspond with the short duration of bilharziasis in the previous study; normal liver scan; D ow nl oa de d by : 54.70.40.11-11/18/20178:35:53PM (3) Studies on pathogenesis [Shamma] showed no liverchanges. In conclusion, these resultsmay dispute Gutlin’Stheory which emphasises that the embryonic and yolk sac arethe onlytissues capable of AFP synthesis, but they will notplay a greater role in screening in our endemiccountry, unlesswe eradicate the disease of bilharziasis.79AcknowledgementGrateful acknowledgement to his Excellency, president Ahmed Hassen Albker, for hisencouragment and great support.Many thanks for Dr. J. Kohn, London, for his advice in preparing this paper, and to my secretaryMiss A. Alsabti.ReferencesAbelev, G. I.; Assecritova, I. V.; Kraevstky, N. A.; Perova, S. D., and Perevodchikova, N. I.:Embryonal serum alpha-globulin in cancer patients diagnostic value. Int. J. Cancer 2: 551–558(1967).Alpert, M. E.: AFP – a serological marker of human hepatoma and embryonal carcinoma. Nat.Cancer Inst. Monogr. 35: 415–420 (1972).Alsabti, E. A. K.: AFP in bilharziasis (unpublished data).Alsaleem, T.: Personal communication.Gitlin, D. and Boesman, M.: J. clin. Invest. 46:1010 (1967).Kohn, J.: Counter immunoelectrophoresis in the detection and identification of AFP. Tumor Res.8:42 (1973).Ruoslahti, E.; Seppala, M.; Vuopio, P.; Saksela, E., and Pelto-kallio, P.: Radioimmunoassay ofAFP in primary and secondary cancer of liver. J. nat. Cancer Inst. 49: 623–630 (1972).Shamma, A. PL: Bilharzial hepatic fibrosis (Shafiek Press, Baghdad 1965).SmithJ. A.: AFP – a possible factor necessary for normal development of embryo. Lancet i: 851(1972). Downloadedby: 54.70.40.11-11/18/20178:35:53PM