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Serous carcinomas of the fallopian tube, uterus, and ovary resemble each other both histologically and in clinical behavior. Comparative genomic hybridization was performed on 20 primary fallopian tube carcinoma specimens to find regions of the genome involved in tubal carcinogenesis and to compare the genomic alterations with those previously detected in serous ovarian and uterine carcinomas. The most frequent changes detected in fallopian tube carcinoma were gains at 3q (70%) and 8q (75%), with high-level amplifications in several cases. Other common gains occurred at 1q, 5p, 7q, 12p, and 20q. The most frequent losses were found at 18q, 8p, 4q, and 5q. The frequency and the pattern of chromosomal changes detected in tubal carcinoma were strikingly similar to those observed in serous ovarian and uterine carcinomas, suggesting common molecular pathogenesis.

Serum levels of human chorionic gonadotropin (hCG), pregnancy-specific beta-1-glycoprotein (SP1), and placental protein 5 (PP5) were measured prior to treatment in 14 patient with hydatidiform mole and in nine patients with choriocarcinoma. Measurement of circulating levels of SP1 and PP5, but not hCG, provides a distinction between benign and malignant gestational trophoblastic tumors.

alpha 2-Macroglobulin (alpha 2M) was demonstrated in normal syncytiotrophoblasts of both early and full-term human placentas using immunocytological staining. alpha 2M was also detected in hydatidiform moles, the benign tumors of proliferating syncytiotrophoblasts. In contrast, no alpha 2M was detected in invasive moles or choriocarcinomas. In culture conditions, both normal syncytiotrophoblasts and choriocarcinoma cells, identified by production of human chorionic gonadotropin, were negative when stained for alpha 2M or when studied using metabolic labeling and immunoprecipitation or radioimmunoassay. However, alpha 2M was taken up from added human serum by the cultured syncytiotrophoblasts, whereas choriocarcinoma cells remained negative also under these conditions. The possible role of alpha 2M in the regulation of proteolysis in cell invasion is considered.

The binding of pregnancy-specific beta-1-glycoprotein (SP1) to Concanavalin A (Con A) has been studied in serum samples from 34 pregnant women and 13 patients with trophoblastic diseases. In normal pregnancy and in hydatidiform moles, the fraction that did not bind to Con A accounted for 0.5--4.3% of the total SP1 concentration whereas, in 5 out of 6 patients with choriocarcinoma, the fraction was 4.8--30%. The secretion of Con A non-binding SP1 appears to be an inherent characteristic of some malignant trophoblast tissues and may result from its altered glycosylation.

Pregnancy-specific beta-1-glycoprotein (PSBG) and human chorionic gonagotrophin (hCG) were measured by specific radioimmunoassays in 73 serum samples from eight patients treated for gestational choriocarcinoma. Both markers were initially present in all cases, but at the time of writing both had levelled off in six cases and decreased markedly in two. Usually hCG was detectable for longer than PSBG during the course of chemotherapy. Both PSBG and hCG reappeared on clinical recurrence. However, at times during the follow-up period one trophoblastic marker only was expressed. This was hCG in most cases, but in one case PSBG alone was encountered. These results suggest that PSBG may serve as an additional marker for the detection of residual tumour growth in patients with trophoblastic tumours.

Twenty-four women, 11 with endometriosis and 13 with fibrocystic mastopathy, were treated with a medium dose (300-400 mg daily) of Danazol for 6 months. The circulating level of progesterone, the 34K insulin-like growth factor-binding protein (IGF-bp) and endometrial protein PP14 (placental protein 14) were measured by specific radioimmunoassays before and during treatment. The serum progesterone concentration decreased significantly during Danazol treatment, as did the serum levels of 34K IGF-bp and PP14. By the third month of therapy amenorrhoea was observed in 22 out of 24 women and this was accompanied by a further decline in the IGF-bp and PP14 levels. In light of the previous observations on the IGF-bp and PP14 synthesis by secretory endometrium and the fact that Danazol causes endometrial atrophy, these results suggest that Danazol treatment has an effect on endometrial protein secretion.

The circulating levels of chorionic gonadotropin, pregnancy specific beta-I-glycoprotein, prolactin and oestradiol were estimated by radioimmunoassay in 219 serum samples from 18 patients with choriocarcinoma and 45 samples from 8 patients with hydatidiform mole. Prolactin and oestradiol concentrations were higher in samples which also contained trophoblastic markers. This difference was also seen in patients with choriocarcinoma and it was not due to chemotherapy, since the difference between hCG positive and hCG negative samples was maintained during chemotherapy. Prolactin was found by immunoperoxidase technique in the syncytiotrophoblast of normal placenta throughout gestation, and also in hydatidiform mole, invasive mole and choriocarcinoma. It is suggested that the malignant syncytiotrophoblast may contribute to circulating prolactin levels either by direct secretion of prolactin or by oestrogen stimulation of the pituitary.

Luteinizing hormone-releasing factor (LRF)-like immunoreactivity was demonstrated by a three layer bridge immunoperoxidase technique in the syncytiotrophoblast of early human placenta, hydatidiform mole and choriocarcinoma. Anti-LRF antiserum was prepared by immunizing rabbits with synthetic LRF coupled to bovine serum albumin (BSA). The immunoreactive site of LRF reacting with the antiserum resided between residues Tyr(5) and Gly(10)-NH2. Syncytiotrophoblast cells of the normal placenta from the first half of pregnancy and trophoblastic tumours, showed staining with anti-LRF antiserum after solid phase immuno-adsorption with Sepharose-coupled BSA. Adjacent control sections showed no staining when prepared with anti-LRF antiserum after immunoadsorption with a Sepharose-coupled LRF-BSA conjugate. The findings of LRF-like material in the placenta prompted us to examine the effect of exogenous LRF on the circulating levels of placental proteins and protein hormones synthesized by the syncytiotrophoblast. Serum levels of chorionic gonadotrophin, pregnancy-specific beta-l-glycoprotein, placental protein five, and placental lactogen remain unaltered for 2 h after an intravenous bolus of LRF (100-300 micrograms) to ten pregnant volunteers admitted for legal abortion between 8 and 18 weeks of gestation. The significance of LRF-like material for the endocrinology of the normal and malignant trophoblast remains to be elucidated.

The human endometrium has been reported to release CA 125 in tissue culture, and elevated levels have been found in patients with endometriosis and adenomyosis. The serum levels of CA 125 were measured in 22 women undergoing hysterectomy for adenomyosis (n = 11) or fibroids (n = 11) of the uterus. In 20 patients (91%) the pre-operative CA 125 level was normal (less than 35 U/ml). All patients with adenomyosis had a normal pre-operative serum CA 125 concentration. Five weeks after the operation the CA 125 levels did not differ from the pre-operative levels. Our results show that the uterine contribution to the serum CA 125 level is minimal, and do not confirm the initial enthusiasm concerning the possible use of levels as an aid in the diagnosis of adenomyosis.

An immunoperoxidase technique was used for the detection of placental protein 5 (PP5) in tissue specimens from trophoblastic tumours. PP5 was detected in all of 15 cases of hydatidiform mole, in two out of six destructive moles and in one of seven choriocarcinomas. Though the biological importance of PP5 is not clear, its association with inactivation of plasmin suggests a role in the control of placental invasiveness.

The circulating levels of four tumor- or trophoblast-associated antigens were measured by specific radioimmunoassays in 11 patients with gestational choriocarcinoma. The estimations were carried out at the time when the urinary gonadotropin (hCG) excretion was low or negligible. Gonadotropin, measured as the hCG beta-subunit, was detected in serum of three patients, one of whom also showed a slightly raised level of carcinoembryonic antigen (CEA). All patients had normal serum alpha-fetoprotein (AFP) levels and no trace of human placental lactogen could be demonstrated. Repeat estimation after treatment of patients with raised levels showed a disappearance or a marked decrease of the circulating hCG levels and a return to normal of the elevated serum CEA level. The results show that although CEA levels may occasionally be elevated new information can hardly be expected from markers other than hCG when one is monitoring response to treatment, but AFP may have potential significance in the distinction between pregnancy and a trophoblastic disease. The circulating levels of hCG are of vital importance in the monitoring of choriocarcinoma patients who appear to be in remission by the conventional analysis of urinary hCG excretion.

The immunoperoxidase technique was used to study the occurrence of placenta-associated plasma protein A (PAPP-A, SP4) in formalin-fixed paraffin-embedded tissue specimens from 15 hydatidiform moles, 6 invasive moles and 7 choriocarcinomas. PAPP-A was found in the syncytiotrophoblast of all hydatidiform moles, in 5 of the 6 invasive moles and in 6 of the 7 choriocarcinomata. No clinical difference was observed between PAPP-A positive and negative cases of invasive disease.

Serum levels of placental protein 10 (PP10) were measured by radioimmunoassay in patients with trophoblastic (n = 23) and non-trophoblastic (n = 122) gynaecological tumours before, during and after treatment. Elevated levels (greater than 2.0 micrograms/l) were found in 96% of patients with an untreated trophoblastic tumour, and in 22%, 20% and 12% of patients with endometrial, cervical and ovarian carcinoma, respectively. After treatment the levels fell in patients with trophoblastic disease. Although PP10 may be tumour-associated in such cases, it is premature to assume any significance for PP10 as a tumour marker in clinical practice, because changes in serum hCG levels are much more informative.

The differential diagnosis of endocervical and endometrial adenocarcinomas can be improved by the demonstration of carcinoembryonic antigen (CEA) in tissue by means of immunoperoxidase staining. Tissue from 131 (80%) of 163 patients with endocervical adenocarcinoma but only 11 (8%) of 137 patients with endometrial adenocarcinoma was CEA-positive. The commonest exceptions were endocervical mesonephroid adenocarcinomas (which were CEA-negative) and endometrial adenosquamous carcinomas (which were CEA-positive). After exclusion of these on simple morphological criteria, 86 of 107 endocervical adenocarcinomas (80%) were CEA-positive, and all 122 endometrial adenocarcinomas were CEA-negative. The remarkable difference in the expression of CEA between endocervical and endometrial adenocarcinomas suggests a novel application of immunohistochemistry in routine clinical practice.