Probes derived from clones bearing cDNAs corresponding to the alpha subunit of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) were used to localize their respective mRNAs cytologically in sections of first trimester and term human placenta. hPL mRNA was exclusively localized to the syncytial layer, hCG alpha mRNA was found in the syncytial layer and also in some differentiating cytotrophoblasts. Hybridization was specific because no signal was observed when labeled pBR322 was hybridized to placental sections or when the placental probes were hybridized to sections of human tonsils. In addition, RNA in placental interstitial cells did not hybridize with hCG alpha and hPL probes. Hybridization with the hCG alpha probe was much greater in first trimester than in term sections, whereas hPL signals were comparable in both first trimester and term placentae. Syncytial formation proceeds through cellular intermediates of cytotrophoblastic origin, and the data suggest that transcription of the hCG alpha gene is initiated before the completion of syncytial formation. In contrast, hPL mRNA synthesis starts later in trophoblast differentiation, likely after the stage of syncytial formation. The data also suggested that hCG alpha mRNA synthesis becomes attenuated but that hPL is transcribed at a rather constant rate during placental development.

The level of tumor-associated antigen (TA-4) was determined in the serum and tumor tissue of patients with squamous cell carcinoma of the cervix by radioimmunoassay and immunoperoxidase techniques. Using an arbitrary limit of 2.5 ng/ml of serum, positive values were observed in 5.5% of healthy controls and 53.6% of patients with cervical squamous carcinoma. The mean value and incidence of elevation of serum TA-4 increased significantly with advancing disease stage. There was, however, no significant increase in serum TA-4 in the early stages of disease. Elevated TA-4 in serum rapidly fell to normal within 72 hours after radical surgery, but remained elevated if complete excision could not be performed. In case of radiotherapy, TA-4 levels in serum and tumor tissue often increased during the administration of the initial 2000 rad, and subsequently declined after the administration of a total of more than 4000 rad. The decline of serum TA-4 to normal observed during radiotherapy was found to be closely correlated with the disappearance of viable cancer cells in histopathologic specimens from the cervix. Immunohistochemical TA-4 staining was present in large cell nonkeratinizing carcinoma, but not in small cell nonkeratinizing carcinoma. These results indicate that the expression of TA-4 antigen in cervical squamous carcinoma is related to differentiation of the tumor cells and that serum TA-4 determination, despite its limitation for early diagnosis, provides a potential means for monitoring the effects of individual therapy for cervical squamous cell carcinoma.

No abstract

The ability of progesterone to modulate the production and secretion of human CG (hCG) in both normal placenta and choriocarcinoma was compared by culturing explants of each trophoblastic tissue in the presence or absence of progesterone. The cellular level of messenger RNAs (mRNAs) encoding hCG alpha, hCG beta, and human placental lactogen (hPL) were quantitatively estimated by mean grain count per syncytial nucleus on the tissue sections hybridized in situ with labeled complementary DNA probes corresponding to these mRNAs. Immunoreactive hCG, hCG alpha, and hCG beta in the media and explanted tissues were measured by the homologous RIAs, and hPL was assayed by hPL-RIA kit. Addition of progesterone at concentrations of 5-20 micrograms/ml into the culture of normal early placenta caused a decrease in the cellular levels of hCG alpha mRNA and hCG beta mRNA after a 24-h culture, and exhibited a decline in immunoreactive hCG and hCG alpha levels released into the media together with a decrease in immunoreactive hCG alpha and hCG beta levels in the explanted tissues after a 48-h culture. The addition of progesterone neither affected the cellular levels of hPL mRNA nor immunoreactive hPL levels in the media and tissues. On the other hand, addition of 17 beta-estradiol at concentrations similar to those used with progesterone did not alter the levels of immunoreactive hCG and hCG alpha in the media or explanted placental tissues, while lower concentrations (1-10 ng/ml) of 17 beta-estradiol caused an increase in immunoreactive hCG alpha levels in the media and cultured tissues. These findings suggest that the suppressive effect observed with progesterone is not likely to be a toxic effect of steroid, but is rather selective on hCG production and secretion by normal placenta. Thus, progesterone may be a factor responsible for the inhibitory regulation of hCG production and secretion by normal placenta. However, in contrast to normal placenta, the choriocarcinoma culture in vitro did not respond to progesterone. The steroid was without significant effect on the cellular levels of hCG alpha mRNA and hCG beta mRNA, and on the levels of immunoreactive hCG and hCG alpha in the media and explanted tissues. These results suggest that the inhibitory regulation of hCG production and secretion in choriocarcinoma is different from that in normal early placenta.

Inside back cover, the entry in the Contents for this article should read: 1200 Cytological distribution of chorionic gonadotropin subunit and placental lactogen messenger RNA in neoplasms derived from human placenta.

No abstract

Normal trophoblast of the human placenta elaborates at least two major protein hormones, chorionic gonadotropin (hCG), and placental lactogen (hPL). There are several gestational trophoblastic diseases of the placenta called hydatidiform mole, invasive mole, and choriocarcinoma. Molar and choriocarcinoma tissues characteristically synthesize large amounts of hCG and small quantities of hPL. To examine the role of trophoblast differentiation in the expression of the hCG and hPL genes, we studied the cytological distribution of their messenger RNA (mRNA) in tissue sections of human hydatidiform mole and choriocarcinoma by in situ hybridization. Histologically, these tissues are in different stages of cellular differentiation. In normal placenta, hCG~ and -/~ mRNA can be localized to some cytotrophoblasts and primarily to the syncytium, whereas hPL mRNA appears only in the syncytial layer. In hydatidiform mole, which still retains placental villous morphology, the hPL gene and hCG and -~ genes are expressed but are poorly localized because of the admixture of cyto-and syncytiotrophoblasts. By contrast, choriocarcinoma, which is devoid of placental villous pattern but in which the cyto-and syncytiotrophoblast-like components are distinguishable, expresses hCG~ and -~ in the syncytial-like areas but little, if any, hPL.These results suggest that a certain level of trophoblast differentiation, such as villous formation, is associated with hPL expression, while the hCG~ gene and the hCG/3 gene can be expressed in more disorganized tissues that contain cytotrophoblastic elements.

A light microscopic analysis of lectin receptors in normal placenta and trophoblastic disease was performed utilizing biotinylated Concanavalin‐A (Con‐A), wheat germ agglutinin (WGA), and peanut agglutinin (PNA), in conjunction with an avidin‐biotin peroxidase complex. Hydatidiform mole, invasive mole and choriocarcinoma exhibited increased receptors to Con‐A and WGA compared to normal placenta. Increased reactivity to Con‐A and WGA was associated merely with increased growth and proliferation of trophoblasts rather than a malignant transformation. Normal placenta, partial and complete mole generally showed moderate to strong binding with PNA after neuramidase treatment, while invasive mole and choriocarcinoma (11 of 15 cases) generally showed minimal to absent reaction with PNA. Heterogeneity of PNA binding in choriocarcinoma was manifested by the presence of PNA reactivity in the trophoblast membrane in 2 cases wherein no prior neuramidase treatment was given. This suggests that in some malignant trophoblasts, there is absence of sialic acid in the terminal cell surface carbohydrate groups resulting in the exposure of N‐acetylgalactoseamine.