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PubMed1986

Pregnancy-specific parameters in early pregnancies after in vitro fertilization: prediction of the course of pregnancy.

The plasma concentrations of the beta subunit of human chorionic gonadotropin (beta-hCG), pregnancy-specific glycoprotein, and progesterone were measured in 37 pregnancies after in vitro fertilization. Twenty-one pregnancies ended with delivery, 9 as clinical abortions, and 7 as biochemical abortions. To predict the pregnancy outcome as early as possible, we designed a prediction graph by calculating a "cutoff line" using discriminant analysis and prediction bands up to 95% probability. This prediction graph can help in the estimation of the probability of pregnancy outcome with satisfactory reliability by determination of beta-hCG only.

Abortion, Spontaneous↗

PubMed1992

Ectopic pregnancy: evolution after treatment with transvaginal methotrexate.

A prospective study was performed with 25 patients with ectopic pregnancies (EPs) who underwent treatment with transvaginal administration of methotrexate. Nineteen patients (76%) had positive responses to this treatment, and six (24%) had to undergo surgery: five because of increasing abdominal pain and one because of vaginal bleeding. The ultrasonographic (US) resolution of the EP was long and lagged behind the resolution at testing of levels of beta subunit of human chorionic gonadotropin (beta-hCG) in all patients. The fallopian tube in 12 (63%) of the responding group initially increased in diameter from a mean of 2.22 cm to a mean of 3.84 cm. In 13 (68%) of the responding group, it became more vascular at color Doppler examination. Eleven (92%) of the 12 EPs that increased in size also became more vascular. The increase in tubal size and vascularity, in spite of the falling beta-hCG level, represents a healing process and should cause no concern about the follow-up of these patients.

Administration, Intravaginal↗

PubMed2004

A case of pediatric ovarian dysgerminoma associated with high serum levels and positive immunohistochemical staining of neuron-specific enolase.

A 5-year-old girl presented with a painful abdominal mass. Abdominal magnetic resonance imaging (MRI) showed 3 separate masses. Tumor markers including lactate dehydrogenase (LDH), cancer antigen-125 (CA-125), beta-subunit of human chorionic gonadotropin (beta-hCG) and neuron-specific enolase (NSE) were elevated. At operation, the main tumor arose from the left ovary and was associated with torsion, whereas the other lesions were lymph node metastases. A salpingo-oophorectomy was performed. Histopathologic examination indicated that the tumor was a dysgerminoma. Immunohistochemicallly, the cells were positive for NSE and placental alkaline phosphatase (PALP) but were negative for CA-125, beta-hCG, S-100, glial fibrillary acidic protein, and vimentin. The elevated serum levels of tumor markers improved dramatically after the operation and chemotherapy.

Alkaline Phosphatase↗

PubMed2000

CSF/serum beta-hCG ratio in patients with brain metastases of gestational trophoblastic tumor.

OBJECTIVE: To assess the accuracy of cerebrospinal fluid (CSF)/serum ratio of beta-subunit of human chorionic gonadotropin (beta-hCG) in detecting brain metastasis of gestational trophoblastic tumor (GTT). STUDY DESIGN: The subjects were ten patients with GTT and brain metastases. Spinal puncture and veni-puncture were performed for measurement of beta-hCG titer in CSF and serum to determine the CSF/serum ratio before starting multiagent chemotherapy and/or brain irradiation. RESULTS: Five patients manifested a CSF/serum beta-hCG ratio > 1/60, and five manifested a ratio < 1/60. CONCLUSION: The CSF/serum beta-hCG ratio is not accurate enough to be routinely considered in the workup, management, and/or surveillance of GTT with brain metastases. Hence, it is perhaps not necessary to perform spinal puncture if the only purpose is to determine the CSF/serum ratio.

Adolescent↗

PubMed1988

Diagnosis of early pregnancy by enzyme immunoassay of Schwangerschafts-protein 1.

Serum Schwangerschafts-protein 1 (SP1) and beta subunit of human chorionic gonadotropin (beta-hCG) were measured by enzyme immunoassay and radioimmunoassay, respectively, in the follicular phase and luteal phase of 50 human menopausal gonadotropin treatment cycles. SP1 could be detected in 63% of blood samples taken in the follicular phase up to the level of 1.56 micrograms/l. Using a cutoff level of 2 micrograms/l, SP1 could be used to diagnose pregnancy 16 to 25 days after the ovulating dose of hCG. The serum SP1 level is not affected by hCG injections and it can be used for diagnosis of pregnancy even when hCG has been given recently. SP1 also may be used as a prognostic indicator of the outcome of the pregnancy.

Abortion, Spontaneous↗

PubMed2001

Treatable subsets in cancer of unknown primary origin.

The purpose of this study was to investigate the treatable subsets in cancer of unknown primary origin (CUP). Fifty patients (27 males and 23 females; median age, 53 years) with CUP diagnosed between April 1992 and June 1999 were analyzed retrospectively. Of the 50 patients, 39 received chemotherapy: platinum-based in 31, non-platinum-based in 4, and clinical trials of new agents in 4. Of the 39 patients, 13 (33.3%; 95% confidence interval: 19.1 - 50.2%) showed objective responses, with 4 complete responders. Patients with poorly differentiated carcinomas in whom beta-subunit of human chorionic gonadotropin (beta-HCG) was elevated more than 10 mIU / ml and female patients with peritoneal adenocarcinomatosis achieved high response rates (83.3% and 80%, respectively) with platinum-based chemotherapy, as compared with only a 15.3% response rate in the remaining patients. Platinum-based chemotherapy provided promising results in patients with poorly differentiated carcinomas and in female patients with peritoneal adenocarcinomatosis. Significantly elevated serum levels of beta-HCG in patients with poorly differentiated carcinoma might predict a better response to platinum-based chemotherapy. However, the investigation of novel chemotherapeutic approaches is warranted for other groups of patients with CUP.

Adenocarcinoma↗

PubMed1990

Elevated sera levels of SP-1 induced by chemotherapy in patients with metastatic gestational trophoblastic diseases.

6 patients with invasive mole and 5 patients with choriocarcinoma were treated from 1983 till 1986. Serum samples were analyzed by simultaneous determining of pregnancy-specific beta-1-glycoprotein (SP-1) using enzyme-linked immunosorbent assay (ELISA) and beta subunit of human chorionic gonadotropin (beta-hCG) using Serono radioimmunoassay kit. In 2 patients with metastatic gestational trophoblastic disease (MGTD) SP-1 peaks were found during chemotherapy. In patients with MGTD with normalized beta-hCG levels a repeated, temporary elevation of isolated SP-1 levels was observed within some months following chemotherapy. After the last isolated peak of SP-1 the pulmonary metastases disappeared. This phenomenon was interpreted as a consequence of the oncolytic process in the affected tissue. In 1 patient with nonmetastatic choriocarcinoma SP-1 ELISA pseudoreaction was found. To recognize these pseudoreactions, a control plate with nonimmunized rabbit IgG was used, simultaneously with SP-1 determinations.

Adolescent↗

PubMed1998

Endometrial adenocarcinoma with trophoblastic differentiation.

OBJECTIVE: To report a case of stage IIIc poorly differentiated endometrial adenocarcinoma with trophoblastic differentiation and to review previously reported cases. METHODS: The clinical course and histopathology of the case were reviewed, and a literature search for other reported cases was performed. RESULTS: The tumor contained syncytiotrophoblast-like giant cells that stained positively for the beta subunit of human chorionic gonadotropin (beta-hCG), and the patient's serum beta-hCG level was elevated (95 mIU/ml), but became undetectable after treatment. Beta-hCG was used as a tumor marker during further therapy. At 16 months' survival, she remains without evidence of disease and with a beta-hCG (level < 5 mIU/ml). Nine other cases of trophoblastic differentiation in gynecologic nontrophoblastic tumors have been reported, five in endometrial carcinomas which we review. CONCLUSIONS: Trophoblastic differentiation in gynecologic nontrophoblastic tumors is rare. Beta-hCG may be useful as a tumor marker in these cases. The clinical behavior of these tumors has been aggressive, with advanced stages at diagnosis, early widespread metastases or recurrences and poor patient outcomes. The patient presented in this report, however, remains without evidence of disease 16 months following diagnosis and may be the longest survivor with this tumor reported to date.

Adenocarcinoma↗

PubMed2004

Detection of circulating breast cancer cells in peripheral blood by a two-marker reverse transcriptase-polymerase chain reaction assay.

The aim of this study was to use a two-marker assay for the detection of breast cancer cells circulating in patients' blood. We have applied a PCR-based methodology to follow up the possibility of the development of metastatic disease in stage I and II patients who had undergone curative surgery. Since the number of circulating cancer cells in peripheral blood is very low, the technique for their detection needs to be not only highly sensitive, but also very specific. The reverse transcriptase-polymerase chain reaction (RT-PCR) technique may improve the sensitivity of breast cancer cell detection up to only a few cells per one million. The principle of the RT-PCR assay is to amplify a messenger RNA characteristic for breast epithelial cells in a blood sample. Since we do not expect such cells to be circulating in peripheral blood of healthy subjects, detection of the characteristic mRNA should indicate the presence of circulating breast cancer cells. We analyzed the usefulness of three mRNA markers: cytokeratin 19 (CK19), mammaglobin (hMAM) and beta subunit of human chorionic gonadotropin (beta-hCG) for this test. Blood samples (112) were obtained from 55 patients, in stages I and II, with or without metastasis to regional lymph nodes (N0 or N1). We found that a two-marker assay increases the sensitivity of detection of breast cancer cells in comparison with a single-marker one. Combination of two tumor-specific mRNA markers, hMAM/CK19 or beta-hCG/CK19, allowed the detection of circulating breast cancer cells in 65% of N1 patients and 38% of N0 patients. By comparison, the combination hMAM/beta-hCG allowed the detection of circulating breast cancer cells in the blood of 68% of N1 patients and 46% of N0 patients. Addition of the third marker did not significantly increase the detection sensitivity.

Base Sequence↗

PubMed1993

Spontaneous resolution of ectopic pregnancy: initial appearance and evolution at transvaginal US.

Spontaneous resolution of ectopic pregnancy (EP) diagnosed with transvaginal ultrasound (US) was confirmed in 13 patients from May 1990 to December 1991. These cases accounted for 24% of the total number of EPs seen in our institution during the same period. These EPs ranged in size from 1 to 3.5 cm, and the beta subunit of human chorionic gonadotropin (beta-hCG) level was less than 1,000 IU/L in all patients. The serum beta-hCG levels became undetectable in 3-45 days (mean, 15.8 days). All EPs had completely resolved at follow-up transvaginal US performed 10-63 days (mean, 30 days) after initial examination. A gestational sac was present in three of these patients, and various degrees of vascularity were detected in four. Four of the resolving EPs increased in size. Four of the nine EPs without detectable flow initially became mildly vascular during the course of resolution. The authors concluded that spontaneous resolution of EP is not an uncommon phenomenon and occurs more commonly in patients with less advanced and less vascular EPs and serum beta-hCG levels less than 1,000 IU/L. EPs can increase in size and become more vascular during their course of resolution.

Adult↗

PubMedDate not supplied

Detection of circulating breast cancer cells with multiple-marker RT-PCR assay.

RT-PCR assay for multiple markers has been shown to increase the detection rate of circulating tumor cells. This assay targeted against cytokeratin 19 (CK19), cytokeratin 20 (CK20) and beta-subunit of human chorionic gonadotropin (beta-hCG) was used to detect circulating breast cancer cells. 5 ml of peripheral blood was drawn before any surgical procedures from 72 breast cancer patients and 30 cases with benign breast disease. Total RNA was extracted from peripheral blood mononuclear cells, reverse-transcripted and amplified. For the benign cases, 10% (3/30) were positive for CK19 and all were negative for CK20 and beta-hCG, whereas 9.72% (7/72), 2.78% (2/72) and 12.5% (9/72) of the malignant cases were positive for CK19, CK20 and beta-hCG respectively. The detection rate of circulating breast cancer cells was unchanged when CK19 was combined with CK20, but it increased to 18.1% (13/72) when the marker was combined with beta-hCG. A significant difference was observed for beta-hCG between benign cases and affected patients with stage II, III and IV disease (p = 0.026). In conclusion, positive RT-PCR signals in blood samples of affected patients correlated with stage, in particular for beta-hCG. CK19/beta-hCG was a promising marker combination.

Adult↗

PubMed1996

Role of endovaginal sonography in the diagnosis and management of ectopic pregnancy.

Although diagnostic laparoscopy is still considered the standard reference in the diagnosis of ectopic pregnancy (EP), use of high-resolution endovaginal sonography, in conjunction with qualitative serum assays of the beta subunit of human chorionic gonadotropin (beta-hCG), allows detection of earlier and smaller EPs. The most common endovaginal sonographic finding of EP (89%-100% of cases) is an extraovarian, round or elongated, solid tubal mass. A tubal ring (an extrauterine saclike structure) is the second most common finding (40%-68% of cases). Pelvic fluid may be present, but it is a nonspecific finding. An EP may have a pseudosac, which can be distinguished sonographically from the true gestational sac of an intrauterine pregnancy. Color Doppler techniques can complement endovaginal sonographic findings, but they should be performed only after a thorough real-time evaluation of the adnexal region. Current therapeutic options for EP include expectant management (ie, close follow-up), medical treatment (usually injections of methotrexate), and surgery. Accurate diagnosis with endovaginal sonography is the prerequisite to nonsurgical management, since surgery is the logical treatment if laparoscopy is used for diagnosis.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMed1993

Pelvic MR imaging findings in gestational trophoblastic disease, incomplete abortion, and ectopic pregnancy: are they specific?

Thirty-nine patients with abnormally elevated levels of serum beta subunit of human chorionic gonadotropin (beta-hCG) were studied to determine whether findings at magnetic resonance (MR) imaging are specific for primary molar disease, persistent gestational trophoblastic disease (GTD), incomplete abortion, and ectopic pregnancy. Among the latter three groups, the only significant differences were a higher prevalence of endometrial distention in the group with incomplete abortion (P < .0035) and the absence of junctional zone disruption in the group with ectopic pregnancy (P < .05). In the group with primary molar disease, total intrauterine volume was significantly increased (P < .001), and endometrial distention and presence of an endometrial mass had a significantly higher prevalence than that in the persistent GTD groups with (P < .04) or without (P < .001) metastases. Myometrial or extrauterine disease was identified in 65% of the patients with persistent disease and a beta-hCG level greater than 500 mIU/mL (500 IU/L). Thus, although MR imaging findings in persistent GTD, incomplete abortion, and ectopic pregnancy are relatively nonspecific, MR imaging can depict invasive disease that may alter therapeutic management in patients with documented GTD.

Abortion, Incomplete↗

PubMed2001

Expectant treatment of ectopic pregnancies: clinical and sonographic predictors.

OBJECTIVE: We identified the potential clinical and sonographic predictors of the spontaneous resolution of ectopic pregnancies. SUBJECTS AND METHODS: We performed a prospective study of 78 consecutive patients with a transvaginal sonographic diagnosis of ectopic pregnancy who had either two consecutive quantitative measurements of their beta subunit of human chorionic gonadotropin (beta-hCG) more than 24 hrs apart or an embryo with a heart beat. We evaluated the patient's age, time from the last menstrual period, beta-hCG level, size of ectopic pregnancy, presence of a gestational sac or embryonic elements, vascularity on color Doppler sonography, peak systolic velocity, and resistive index of ectopic pregnancy at the time of presentation as potential independent predictors of the final outcome. Logistic regression was performed to identify the independent predictors. RESULTS: Forty-six patients had declining beta-hCG levels, and 32 ectopic pregnancies showed an embryo with a heart beat or had steady or rising beta-hCG levels. Univariate analysis indicated that a longer time from the last menstrual period (older ectopic pregnancies), lower beta-hCG levels, and the absence of gestational sac are statistically more significantly seen in ectopic pregnancies with declining beta-hCG levels (p < 0.05). Resistive index of ectopic pregnancy reached borderline significance (p = 0.05). In a multiple logistic model, the same variables were independent predictors of outcome (p < 0.05). Resistive index was also a predictor (p = 0.09). CONCLUSION: Longer times from the last menstrual period, lower beta-hCG levels, absence of gestational sacs, and higher resistive indexes of ectopic pregnancy at the time of presentation appear to be independent predictors of the spontaneous resolution of ectopic pregnancy.

Adult↗

PubMed2003

Surgery-related shedding of breast cancer cells as determined by RT-PCR assay.

BACKGROUND AND OBJECTIVES: Surgery could result in the shedding of cancer cells into the circulation. These cells were investigated with reverse transcriptase-polymerase chain reaction (RT-PCR) assay for cytokeratin 19 (CK19) and beta-subunit of human chorionic gonadotropin (beta-hCG). PATIENTS AND METHODS: Peripheral blood was sampled from 49 patients with breast cancer before operation (d(-1)), 1 day after operation (d(1)), and 7 days after operation (d(7)). Total RNA was extracted from peripheral blood mononuclear cells, followed by RT-PCR assay. The products for beta-hCG were digested with Sty I endonuclease. The patients were followed up for a median of 33 months for signs of recurrence and metastasis. RESULTS: The results for CK19 at d(-1), d(1), and d(7) were 8.2, 20.4, and 10.2%, respectively. For beta-hCG, the corresponding results were 12.2, 26.5, and 16.3%, respectively. There was a higher positive rate in d(1) samples than in d(-1) samples for CK19 and beta-hCG (P < 0.05 and P = 0.092, respectively). Conversions of signals from being negative to positive were found in all stages. These did not demonstrate a statistical correlation with prognostic factors associated with a poor prognosis. Only two of the five recurrence occurred in the 15 patients with the signal conversions, while the other three occurred in the patients showing no signals in all samples. CONCLUSIONS: Cancerous breast cells that enter into the blood circulation as a result of an operation are unlikely to be involved in the formation of metastatic deposits.

Adult↗

PubMed2006

Ten tandem repeats of beta-hCG 109-118 enhance immunogenicity and anti-tumor effects of beta-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65.

The beta-subunit of human chorionic gonadotropin (beta-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of beta-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with beta-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-betahCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residue sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-betahCGCTP37 and HSP65-betahCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-betahCGCTP37 elicited much higher levels of specific anti-beta-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-betahCGCTP37, which should suggest that HSP65-X10-betahCGCTP37 may be an effective protein vaccine for the treatment of beta-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens.

Amino Acid Sequence↗

PubMed2002

Serum HCG beta, CA 72-4 and CEA are independent prognostic factors in colorectal cancer.

In colorectal cancer, stage is considered to be the strongest prognostic factor, but also serum tumour markers have been reported to be of prognostic value. The aim of our study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4 and free beta subunit of human chorionic gonadotropin (hCG beta) in colorectal cancer. Preoperative serum samples were obtained from 204 colorectal cancer patients, including 31 patients with Dukes' A, 70 with Dukes' B, 49 with Dukes' C and 54 with Dukes' D cancer. The serum levels of CEA, CA 19-9, CA 242 and CA 72-4 were measured with commercial kits with cut-off values of 5 microg/L for CEA, 37 kU/L for CA 19-9, 20 kU/L for CA 242 and 6 kU/L for CA 72-4. The serum hCG beta was quantitated by an immunofluorometric assay (IFMA) with 2 pmol/L as a cut-off value. Survival analyses were performed with Kaplan-Meier life tables, log-rank test and Cox proportional hazards model. The sensitivity was 44% for CEA, 26% for CA 19-9, 36% for CA 242, 27% for CA 72-4 and 16% for hCG beta. The overall 5-year survival was 55%, and in Dukes' A, B, C and D cancers the survival was 89%, 77%, 52% and 3%, respectively. Elevated serum values of all markers correlated with worse survival (p < 0.001). In Cox multivariate analysis, the strongest prognostic factor was Dukes' stage (p < 0.001), followed by tumour location (p = 0.002) and preoperative serum markers hCG beta (p = 0.002), CA 72-4 (p = 0.003) and CEA (p = 0.005). In conclusion, elevated CEA, CA 19-9, CA 242, CA 72-4 and hCG beta relate to poor outcome in colorectal cancer. In multivariate analysis, independent prognostic significance was observed with hCG beta, CA 72-4 and CEA.

Adult↗

PubMed2000

Fine needle aspiration may shed breast cells into peripheral blood as determined by RT-PCR.

OBJECTIVE: A diagnostic test applying reverse-transcriptase chain reaction (RT-PCR) assay targeted against cytokeratin 19 (CK19), cytokeratin 20 (CK20) and the beta-subunit of human chorionic gonadotropin (beta-hCG) mRNAs was used to evaluate the impact of fine needle aspiration (FNA) on breast cell shedding into peripheral blood. METHODS: The sensitivity of this assay was based on the different degree of admix of MCF-7 breast cancer cell line with HL-60 leukemic cell line. For blood samples of 24 cases with benign breast diseases and 20 cases with malignant ones, 5 ml of peripheral blood was drawn before and within 10 min after puncture. Total RNA was extracted from peripheral blood mononuclear (PBMN) cells; beta-actin was used to assess the quality of cDNA. RT-PCR products were run in ethidium bromide gel and observed under ultraviolet. RT-PCR products for beta-hCG were digested with Sty I endonuclease to confirm the specificity. RESULTS: The sensitivity of RT-PCR assay was 1 MCF-7 cell in 10(5) HL-60 cells for CK19 and CK20, and 1 in 10(6) for beta-hCG. For 24 benign cases, none of the pre- FNA samples was positive for CK20 and beta-hCG, and 3 cases (12.5%) were positive for CK19. As for 20 malignant cases, 1 pre-FNA sample was positive for all three markers and 2 other samples were positive for CK19. After aspiration, 3/21 benign cases and 1/17 malignant case with pre-FNA negative signals became positive for CK19, while 3/19 malignant cases with pre-FNA negative signals were converted to a positive result for CK20 and beta-hCG. Of 6 pre-FNA positive cases, all cases remained positive for the respective marker. CONCLUSION: FNA to breast tumor may cause hematogenous dissemination of breast cells.

Adult↗