G. Crombach

Detection of squamous cell carcinoma antigen in normal squamous epithelia and in squamous cell carcinomas of the uterine cervix.

Squamous cell carcinoma (SCC) antigen is a subfraction of tumor antigen TA‐4 isolated from a cervical squamous cell carcinoma. The specificity of SCC antigen and the factors influencing its release into serum were evaluated. Antigen concentrations were measured in 157 tissue extracts and in 188 sera of patients with nonmalignant or malignant gynecologic diseases. A commercial radioimmunoassay based on polyclonal antibodies (Abbott Laboratories, North Chicago) was used. Cytosol concentrations were significantly higher (P < 0.005) in normal squamous epithelia (x̃ = 6040 ng/mg cell protein [CP]) and in squamous cell carcinomas (x̃ = 2483 ng/mg CP) of the exocervix than those in normal columnar epithelia and in adenocarcinomas of the endocervix, endometrium, ovary, and breast (x̃ = 1–508 ng/mg CP). Despite the high antigen concentrations in normal squamous epithelia, elevated serum levels (>2.5 ng/ml) were almost exclusively found in patients with cervical squamous cell carcinomas. The sensitivity of SCC antigen as a marker for primary carcinomas was 61%, increasing from 29% in Stage I to 89% in Stage IV. The positivity rate was higher in women with well‐differentiated (78%) and moderately differentiated carcinomas (67%) than in those with poorly differentiated tumors (38%). The results show that SCC antigen is not tumor specific. The release into serum is independent of local tissue content, but is apparently influenced by the infiltrative growth, the mass, and the degree of histologic differentiation of the tumor.

CA 125 in normal tissues and carcinomas of the uterine cervix, endometrium and Fallopian tube. II. Immunoradiometric determination in secretions, tissue extracts and serum.

SummaryThe study deals with the occurrence of cancer antigen 125 (CA 125) in the normal and neoplastic uterine cervix, endometrium and fallopian tube and its applicability as a tumour marker. CA 125 concentrations were measured in 52 secretion specimens, in cytosol fractions of 97 tissue biopsies and in serum from 47 women with nonmalignant disorders and from 334 patients with carcinomas. High quantities of CA 125 (780-454860 U/ml) were detected in cervical mucus, intra-uterine and tubal fluid, exceeding those in the corresponding serum samples by factors of up to 2000. CA 125 concentrations were 9–53 fold higher in cytosol fractions of normal and neoplastic glandular epithelia of the endocervix and endometrium than in those of cervical squamous epithelia and the cervical wall. Despite similarly high antigen concentrations in normal glandular epithelia and adenocarcinomas serum levels elevated to above 65 U/ml were only found in patients with malignant tumours. The positivity rates in serum increased with tumour extent and were 0–43% for primary and 63–79% for recurrent cervical, endometrial and tubal adenocarcinomas. During long-term follow-up, CA 125 serum concentrations were concordant with the clinical course in 10 out of 11 patients with progressive carcinomas. According to these results, the release of CA 125 into the peripheral blood is apparently dependent on the infiltrative growth and the mass of the tumour rather than on, the local tissue concentrations. The clinical use of CA 125 is limited to the detection of advanced adenocarcinomas of the Müllerian duct.

Radioimmunoassay of Laminin P1 in Body Fluids of Pregnant Women, Patients with Gynaecological Cancer and Controls

Laminin P1, a pepsin-resistant fragment of the glycoprotein laminin, was determined in body fluids using a double-antibody radioimmunoassay. The median serum concentrations found were: men 1.32, premenopausal women 1.22, postmenopausal women 1.38 and pregnant women (35th gestational week) 2.18 U/ml. The median concentration in amniotic fluid was 1.90, in urine 0.28 and in follicle cyst fluid 1.74 U/ml. During gestation, rising serum levels of up to 5 U/ml were observed which decreased within a few days after delivery. The cut-off value of laminin P1 for 95% specificity of the normal female control group was found to be 1.8 U/ml. The frequencies of elevated serum concentrations were 11, 18, 23 and 33% in patients with primary malignant lesions of the breast, endometrium, cervix and ovary, respectively, and rose up to 50-51% in patients with recurrent or metastatic gynaecological cancer. Laminin P1 was found in high concentrations in the cytosol fractions of breast cancer biopsies. Long-term sequential determinations of serum levels in 10 individual patients with progressive cancer reflected the course of the disease in 8 cases. Although laminin P1 can be considered as a tumour-associated protein, low sensitivity to primary cancer and insufficient specificity limit its application as a tumour marker and its usefulness in monitoring of patients with gynaecological cancer.

Relationship between amniotic fluid insulin and maternal blood glucose concentrations in patients with carbohydrate intolerance during pregnancy

In contrast to maternal blood glucose, amniotic fluid insulin (AFI) directly reflects the functional state of the fetal pancreas. In a prospective study we evaluated the correlation of AFI with maternal metabolic control in 70 amniotic fluid specimens from 61 women having carbohydrate intolerance during pregnancy (White A n = 44, B0 n = 17). AFI was measured with the Insulin RIA 100 kit from Pharmacia (Freiburg). The normal range of AFI was established in 304 healthy pregnant women (16th-42nd gestational week). AFI concentrations increased by a factor of 1.5 to 2 during gestation reflecting the maturation of the fetal pancreas. Elevated AFI levels (> 97th centile) were found in 11% of normoglycemic diabetics and in 50% of women with insufficient metabolic control. Despite a high overall concordance (81%) no direct relationship could be found between fetal and maternal parameters. Patients with increased AFI values had a 5-fold higher rate of large-for-gestational age (LGA) infants than women with normal levels. This finding confirms the pathogenetic role of hyperinsulinism in the development of fetal macrosomia.

Expression of pS2 protein in breast cancer

SummaryThe pS2 protein was first detected in the oestrogen-dependent breast cancer cell line MCF-7. It may have prognostic value for primary breast cancer, and could be used to predict clinical responsiveness to endocrine therapy. In a retrospective study, the concentrations of pS2 protein were determined in 434 cytosol specimens using an immunoradiometric assay. The median values (4, 6 and 3 ng/mg protein) and the third quartiles (27, 26 and 29 ng/mg) in benign breast tumours (n=17), and in primary (n=325) and recurrent (n=37) breast carcinomas were of the same order of magnitude. In primary breast cancer, high pS2 values (>26 ng/mg) correlated significantly with a positive oestrogen receptor (ER) status and a high grade of tumour differentiation (P=0.01). As many as 85% of the pS2 positive tumours were ER positive. A marginally significant correlation (P=0.06) was also found between pS2 status and the quantitative expression of the ER. However, the pS2 values in ER positive endometrial carcinomas (n=12) as well as in other benign and malignant genital tumours (n=43) were more than 30 times lower than those measured in breast tumours. The results reveal a close association between pS2 protein and ER status which appears to be limited to breast cancer.

Vergleich der immunhistochemischen und biochemischen Bestimmung von Kathepsin D beim primären Mammakarzinom

Die Konzentration der lysosomalen Protease Kathepsin D im Tumorzytosol soll vor allem bei lymphknotennegativen Mammakarzinomen prognostische Bedeutung haben (Rochefort et al.; Spyratos et al.; Tandon et al.).