Ectopic Production of Chorionic Gonadotropin and Its Subunits by Islet-Cell Tumors

Cr, Kahn; Sw, Rosen; Bd, Weintraub; Ss, Fajans; Görden, Phillip

doi:10.1056/nejm197709152971101

Cited by 169 publications

(31 citation statements)

References 25 publications

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“…In a previous study, the hCG-like material found in urine and blood from patients with germ cell tumours appeared to be mainly intact hCG, while material from the patient with a metastatic bladder tumour consisted principally of free beta subunit (Norman et al, 1985). Variability of the relative concentration of intact hormone and free subunits, together with heterogeneous glycosylation of the protein chains, has also been reported in studies on patients with a variety of other tumour types (Weintraub & Rosen, 1973;Rosen & Weintraub, 1974;Kahn et al, 1977;Yoshimoto et al, 1979b). The degree of glycosylation affects various biochemical characteristics and also the rate of metabolism in vivo (Van Hall et al, 1971;Tsuruhara et al, 1972).…”

Section: Resultsmentioning

confidence: 73%

In vitro secretion of human chorionic gonadotrophin by bladder tumour cells

Iles¹,

Oliver²,

Kitau³

et al. 1987

Br J Cancer

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Summary Human chorionic gonadotrophin (hCG) and alphafetoprotein (AFP) were measured in culture media from a panel of 29 cell lines including 9 bladder carcinomas, 5 'normal' bladder epithelia, 10 germ cell tumours, and 5 miscellaneous tumours and 'normal' cell lines. In 7 of the 9 bladder carcinomas and 4 of the 5 'normal' bladder epithelia, the media contained hCG at levels ranging from between 34 and 3,600 IU I -. All other cell lines, including the 10 germ cell tumour lines gave negative results for hCG. These findings indicate that in vitro secretion of hCG is a common feature of normal and neoplastic bladder transitional epithelia, and support the hypothesis that parts of the genito-urinary epithelium have a potential for hCG production.The high incidence of elevated levels of human chorionic gonadotrophin (hCG) and alphafetoprotein (AFP) in association with testicular germ cell tumours is wellrecognised in vivo (Seppala et al., 1986), but this phenomenon is relatively uncommon during culture of these tumours (Andrews et al., 1980). Ectopic production of hCG is also a well-recognised phenomenon in some non-gonadal epithelial tumours (Braunstein et al., 1973;McManus et al., 1976;Bellet et al., 1980). This is particularly common in gastric (24%), hepatic (17%) and pancreatic (50%) cancers (reviewed by Baylin & Mendelsohn, 1980;Heyderman et al., 1985;Seppala, 1986 al., 1986). Immunohistochemical studies suggest that ectopic production of hCG is relatively unusual in bladder tumours with reports varying from 5 of 13 to 12 of 104 cases (Rodenburg et al., 1985;Shah et al., 1986). In the present study we have examined hCG and AFP secretion by normal and neoplastic bladder and testicular germ cell tumours in vitro. Materials and methodsA total of 29 cell lines were examined in this study (Table I). They included: 14 lines of urothelial origin (9 neoplastic (see Table I), 5 'normal'); 10 germ cell tumours (gonadal) and 5 miscellaneous tumours and 'normal' controls. The American Type Culture Collection (ATCC) and other lines held at the London Hospital were grown in a medium consisting of Leibowitz L-15 RPMI 1640 (50/50, v/v) containing 20% heat inactivated foetal calf serum (FCS), transferrin (4 pg ml -1), hydrocortisone (4 ng ml -1), insulin (4 Mg ml -1), and penicillin-streptomycin (1,000 U ml-1) (Gibco Ltd., Paisley, Scotland). Cell lines from the Institute of Urology were grown RPMI 1640 plus 5% FCS (Gibco). Incubation was carried out at 37°C in a mixture of 95% air and 5% CO2. The cell lines were grown to confluence in culture flasks (75 cm adherence area; Falcon Labware).

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Section: Resultsmentioning

confidence: 73%

In vitro secretion of human chorionic gonadotrophin by bladder tumour cells

Iles¹,

Oliver²,

Kitau³

et al. 1987

Br J Cancer

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“…Recently other grouips have also documented increases in a levels in benign as well as malignant conditions (Dosogne-Guerin et al, 1978;Braunstein et al, 1979). These observations are at variance with results of a study of patients with pancreatic islet-cell tumours, in which serum of subunit was high only in malignant tumours, and normal in benign cases (Kahn et al, 1977).…”

Section: Resultsmentioning

confidence: 84%

Serum glycoprotein hormone α subunit, hormone receptors and disease stage in patients with breast cancer

MacFarlane¹,

Barnes²,

Howat³

et al. 1980

Br J Cancer

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Summary.-The concentration of the common a subunit of the glycoprotein hormones was high in the serum of 21/56 (38o%) of premenopausal patients and 22/106 (21 %) of postmenopausal patients with primary breast cancer, at the time of presentation. 7/59 (12%) of patients with benign disease also had high a subunit levels. Tumour cytosol oestrogen and progesterone receptor status was determined in 80% of the patients with cancer, and there was a trend towards higher a levels in patients without receptors, but this was not statistically significant. In the premenopausal patients with cancer there was a significant correlation between a subunit level and disease stage, R=0.47, P=0.0001, but not in the postmenopausal patients. In view of the correlation with disease stage, high levels of a subunit in premenopausal patients with breast cancer at presentation with the primary tumour may indicate poor prognosis.THE COMMON ax subunit of the glycoprotein hormones (thyroid-stimulating hormone-TSH; follicle-stimulating hormone FSH; luteinizing hormone LH, and chorionic gonadotrophin hCG) has been found in breast-tumour cultures (Cove et al., 1979; Miller et al., unpubl.). Immunoperoxidase staining has demonstrated the presence of oa subunit in histological specimens of breast carcinomas, and lymph-node metastases found at the initial operation are said to be common in patients with ay subunit-positive primary tumours (Walker, 1978).Increased concentrations of oa subunit have been found in the serum of persons with various benign and malignant conditions (Dosogne-Guerin et al., 1978;Braunstein et al., 1979) and we report here a study of serum a subunit levels in a large consecutive series of patients presenting with primary breast cancer, and compare them with oa subunit levels in patients with benign breast disease and a normal control population. In order to define the importance of serum oa subunit measurement in our breast-cancer patients, we have correlated oa levels with the tumour hormonereceptor status and disease stage at removal of the primary tumour, both factors known to influence patient survival (Say & Donegan, 1974; Hahnel et al., 1979 and 106 postmenopausal patients, median age 61 yrs (range 33-82).

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“…Recent studies, for example, have shown that the presence of the alpha chain of human chorionic gonadotropin (HCG) both in the plasma and in tissues is highly predictive of malignant behavior in these tumors (23). Biological behavior may also be correlated with the major hormonal species secreted by the tumor (6).…”

Section: Pancreatic Endocrine Cellsmentioning

confidence: 99%

“…These widely dispersed cells contain a set of common enzymes, including neuron-specific enolase (34). It has also become apparent that many of the gut hormones are also present within the nervous system where they arè Presented as part of the program at the 1982 Joint Meeting of the American and Japanese Histochemical Societies, held in Vancouver, British Columbia, Canada, July [20][21][22][23][24]1982.…”

Section: Introductionmentioning

confidence: 99%