K. Robert McIntire

SERUM-ALPHA-FETOPROTEIN LEVELS IN PATIENTS WITH ATAXIA-TELANGIECTASIA

Abstract The serum-α-fetoprotein concentrations of twenty patients with ataxia-telangiectasia, one hundred and forty-nine normal children and adults, fifteen siblings and eleven parents of patients with ataxia-telangiectasia, and fifty-four patients with other immunodeficiency states were measured using a sensitive double-antibody radioimmunoassay. All serum-α-fetoprotein concentrations in patients with ataxia-telangiectasia studied were above 30 ng. per ml. (range 44-2800 ng. per ml.). None of the siblings or parents of patients with ataxia-telangiectasia or patients with various other immunodeficiency diseases had α-fetoprotein levels above 30 ng. per ml. Thus ataxia-telangiectasia seems to be unique among the major immunodeficiency diseases in its association with a raised α-fetoprotein level. The synthesis of this fetal pro tein of hepatic origin by patients with ataxia telangiectasia sud=ggests that liver is not fully developed in these patients. These findings support the hypothesis that a primary abnormality of patients with ataxia-telangiectasia is a defect in tissue differenciation. This abnormality may be due to a defective interaction between the entodermal and mesodermal germ lines, an interaction that seems to be required for the differentiation of gut-associated organs such as the thymus and liver.

Cellular localization of alpha-fetoprotein and human chorionic gonadotropin in germ cell tumors of the testis using an indirect immunoperoxidase technique. A new approach to classification utilizing tumor markers

An immunohistologic study of 21 patients with germ cell tumors of the testis with measured serum levels of chorionic gonadotropin (HCG) and alpha‐feto protein (AFP) was undertaken to correlate the various types of neoplasms with the presence of these tumor markers in the tissue and serum. AFP was demonstrated in mononuclear embryonal cells within embryonal carcinoma and endodermal sinus tumor. HCG was identified within syncytiotrophoblastic giant cells, frequently in association with embryonal carcinoma, and rarely with endodermal sinus tumor and seminoma, as well as in the syncytiotrophoblastic component of choriocarcinoma. Eighteen of the 21 patients (86%) had elevated tumor markers in their serum; serum HCG alone was elevated in five (24%), AFP alone in five (24%) and both were elevated in eight (38%). There was tissue localization of HCG in 12 of the 13 patients (92%) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53%) with elevated serum AFP levels. Based on these findings, a tentative immunohistologic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma, adult type, is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma and teratoma are unlikely to be associated with either marker.

The use of a radioimmunoassay for alpha-fetoprotein in the diagnosis of malignancy.

Using a double antibody radioimmunoassay test, α‐fetoprotein was elevated (i.e., over 40 ng/ml) in 72% of patients with hepatocellular carcinoma, 75% of patients with teratocarcinoma or embryonal cell carcinoma of the testis, 23% of patients with pancreatic carcinoma, 18% of patients with gastric carcinoma, 5% of patients with colonic carcinoma, and 7% of patients with bronchogenic carcinoma studied. In contrast to these positive findings in patients with cancer, none of the 210 normal controls over 1 year of age and only 1 of the 300 patients with chronic nonhepatic diseases other than ataxia telangiectasia had elevated levels. All of the 40 patients studied with the immunodeficiency disease, ataxia telangiectasia, had elevated AFP levels in accord with the view that these patients have a defect in organ differentiation. The radioimmunoassay for AFP was of special value in monitoring the effectiveness of therapy of certain forms of malignancy (e.g., hepatocellular carcinoma, embryonal cell carcinoma, and teratocarcinoma of the testis), since the product of a few tumor cells was detectable with this assay when AFP was undetectable as assessed by agar diffusion tests and when the residual tumor could not be detected by other clinical parameters.

The Value of Serum Tumor Markers in the Staging and Prognosis of Germ Cell Tumors of the Testis

AbstractDuring a 3-year prospective study serum chorionic gonadotropin, alpha-fetoprotein and plasma carcinoembryonic antigen were measured in 111 patients with germ cell tumors of the testis. Either human chorionic gonadotropin or alpha-fetoprotein levels were elevated in 91 per cent of the patients with clinically demonstrable non-seminomatous tumors. Among 24 patients who had recurrent disease 16 (67 per cent) had elevated alpha-fetoprotein or human chorionic gonadotropin at a time when recurrence was clinically undetectable. All patients free of tumor had normal levels of human chorionic gonadotropin or alpha-fetoprotein, there being no falsely positive values. Carcinoembryonic antigen was elevated in 33 per cent of patients with seminoma and in 7 per cent of patients with non-seminomatous tumor but carcinoembyonic antigen levels did not correlate with the course of the disease. Determinations of human chorionic gonadotropin and alpha-fetoprotein before lymphadenectomy decreased the error in clinical ...

Discordance of human chorionic gonadotropin and alpha-fetoprotein in testicular teratocarcinomas.

Human chorionic gonadotropin (hCG) and elevated levels of alpha‐fetoprotein (αFP) were present in the plasma of three patients with metastatic testicular teratocarcinoma. Initial chemotherapy resulted in the disappearance of the hCG and a decrease in the αFP levels in all three patients. Two of the patients had persistently elevated levels of αFP with undetectable hCG, while the αFP in the third patient decreased to and remained in the normal range despite reemergence of high plasma levels of hCG. The discordant behavior of these two proteins indicates that their cells of origin are probably different. When both hCG and αFP are present in the blood of patients with testicular tumors, each should be followed in order to determine the adequacy of therapy.

The value of serial measurement of both human chorionic gonadotropin and alpha-fetoprotein for monitoring germinal cell tumors

Quantitative serial serum measurements of human chorionic gonadotropin (hCG) and alpha‐fetoprotein (AFP) levels using sensitive double‐antibody radio‐immunoassays were performed in nine patients with germinal cell tumors before and during treatment. The sera of eight of the nine were found to have a hCG marker and five of the nine an AFP marker. The sera of four patients were found to have both. Serial serum levels of hCG, of AFP, or both were useful for monitoring disease activity during therapy in all nine patients. In two patients tumor masses failed to diminish during chemotherapy, but the tumor markers fell appropriately. At surgery one patient had a mature teratoma, the other a mature teratoma with a microscopic focus of an embryonal cell tumor. In one patient tumor reactivation was reflected by the emergence of only one of two previously elevated tumor markers. One patient had a rise in hCG, another a rise in both markers coincident with recurrence of tumor. Serial measurements of AFP and hCG are useful for following the response to therapy of germinal tumors, and can assist in making therapeutic decisions.

Serum α-Fetoprotein in Patients with Massive Hepatic Necrosis

Serum concentrations of a-fetoprotein (AFP) were measured by radioimmunoassay in 12 patients with massive hepatic necrosis, 11 of whom died. Levels were significantly elevated after the 8th day of illness in 8 of the 9 patients who died between the 10th and 60th day, and in the 1 patient who survived. All 9 patients with increased levels of serum AFP exhibited histological evidence of hepatic regeneration. These findings indicate that the rise in serum AFP in massive hepatic necrosis is related to the duration of survival after the onset of illness, but does not necessarily imply ultimate recovery. Because available evidence suggests that the serum AFP level reflects hepatic regenerative activity, it appears that the onset of regeneration in fulminant hepatitis is delayed until the 2nd week of illness.

Serum alpha fetoprotein concentration and tumor growth dissociation in a patient with ovarian teratocarcinoma

A 17‐year‐old girl with a malignant ovarian teratoma had an elevated concentration of alpha fetoprotein detected in her serum by an electroimmunodiffusion technique when first seen. Surgery and chemotherapy resulted in regression of all measurable disease and a decrease in alpha fetoprotein level which was not detectable by the electroimmunodiffusion technique. A radioimmunoassay technique demonstrated the decrease in serum concentration of alpha fetoprotein and continuing decrease even though there was subsequent recurrence of tumor. Thus, the disease activity in malignant ovarian teratoma may not always correlate well with serum alpha fetoprotein concentration.

Serum alpha-fetoprotein in 184 Ugandan patients with hepatocellular carcinoma: clinical laboratory and histopathologic correlations.

Qualitative serum alpha‐fetoprotein (AFP) determinations were done on sera from 184 Ugandan patients with hepatocellular carcinoma (HC) and the results correlated with clinical, laboratory, and histopathologic features of the disease. One hundred twenty‐one (66%) were AFP positive. Young patients and those with concomitant hepatitis B antigenemia (HBAg) were AFP positive significantly more frequently than older and HBAg negative patients. There were no differences in AFP frequency between patients with or without antibody to HBAg. There was also a tendency for men and patients with poorly‐differentiated tumors to be positive more frequently than women or patients with well‐differentiated tumors. No correlations with AFP elevation were found for duration of symptoms prior to diagnosis, disease stage, patient survival, standard tests of liver function, elevations of serum proline hydroxylase or serum chorionic gonadotropin, or the presence of concomitant cirrhosis. Sensitive, standardized, quantitative AFP tests should be used in future correlative studies with special emphasis placed on patient age and HBAg.

The Role of the Radioimmunoassay of Serum Alpha-Fetoprotein and Human Chorionic Gonadotropin in the Intensive Chemotherapy and Surgery of Metastatic Testicular Tumors

Quantitative measurement of serum alpha-fetoprotein and human chorionic gonadotropin by double antibody radioimmunoassays reflects the efficacy of surgical, radiation and/or chemotherapeutic regimens in patients with bulky disseminated testicular tumors. When these therapies are effective they produce an immediate decrease in serum levels of these markers that reflects the decrease in tumor size and could be as rapid as the catabolic decay rate for alpha-fetoprotein or human chorionic gonadotropin. The alpha subunit of human chorionic gonadotropin has a short half-life (20 minutes) and has been used for the first time to localize a recurrent metastatic testicular tumor. Cellular localization of these markers by immunochemical techniques has helped us to understand the natural history of this cancer and the cell types responsible for production of the markers.