Tumor-associated Antigen CA Research Articles

Evaluation of a novel ELISA for the tumor-associated antigen CA 72-4 in patients with ovarian cancer.

Aim:Cancer antigen 72–4 (CA 72–4) is an established tumor marker in ovarian cancer. We evaluated a new solid-phase ELISA (DRG TM-CA 72–4 ELISA).Materials & methods:Repeated measures of test samples and controls were performed to evaluate reliability and reproducibility. Afterward, we performed analyses on the sera of 150 patients with primarily diagnosed ovarian cancer. Results were compared with those of the Cobas CA 72–4 kit. Results were correlated with clinical patient data.Results:Results of the DRG TM-CA 72–4 ELISA were reproducible with acceptable deviations within measures, and the measured CA 72–4 serum concentrations were well in accordance with the references. High concentrations were significantly associated with grading, tumor stage and tumor residuals after surgery.

Clinical significance of the circulating tumor-associated antigen CA 19-9 in cancers of the digestive tract

The relevance of the tumour associated antigen CA 19-9, defined by a monoclonal antibody, was investigated in 471 patients with carcinomas of the gastrointestinal tract and in 100 patients with benign diseases of the abdomen. In the early stages of gastric and colorectal carcinomas the sensitivity of the CA 19-9 test was between 10 and 25% and increased to about 50% in tumour stage IV. Detection rate in pancreatic carcinoma was 88% and thus markedly higher. The specificity of the test, as against the group of benign abdominal diseases, was 95%. Postoperative CA 19-9 follow-up showed unaltered individual baseline values in 192 out of 196 cases without clinical evidence of tumour progression. However, in 40 out of 61 cases (66%) with recurrencies or metastases continuous increases of CA 19-9 were observed which preceded the clinical relapse by up to 16 months (median 2 months). Concomitant determination of CEA increased sensitivity to 90% due to partial complementary information. This was particularly pronounced in gastric carcinomas in whom continuous increases of CEA involved only 58% of all patients with tumour progression. By simultaneous determination of both tumour markers this ratio rose by increases of both or one antigen to 83%.

Diagnostic importance of the tumor marker CA 19-9 in pancreatic cancer

The diagnostic value of the tumour-associated antigen CA 19-9 was tested in 309 patients, 156 with malignancies (39 carcinoma of the pancreas, 117 extrapancreatic malignant tumour) and 153 patients with non-malignant disease (54 chronic pancreatitis, 25 acute pancreatitis, 74 general surgical disease). Levels above the normal range of 6-37 U/ml were obtained in 95% of patients with carcinoma of the pancreas (mean value 528 U/ml), in 31% of patients with gastric carcinoma and 16% with colorectal carcinoma (mean 8 U/ml). Results of the pre-operative determination of CA 19-9 indicated for carcinoma of the pancreas a sensitivity of 95%, a specificity of 87% and an overall accuracy of 88%. Pre-operatively elevated CA 19-9 concentrations in patients with carcinoma of the pancreas fell to normal after curative resection of the neoplasm. After palliative operation or in inoperable carcinoma CA 19-9 serum concentrations were never less than 37 U/ml.

Importance of the tumor-associated antigen CA 19-9 in the differential diagnosis of pancreatic diseases

Tumour-associated antigen CA 19-9 was determined in serum from 166 patients (30 without gastro-intestinal disease, 32 with liver cirrhosis, 9 with choledocholithiasis, 65 with acute or chronic pancreatitis and 30 with malignant tumors in the region of pancreas and bile passages). The specificity of CA-19-9 as tumour marker was 97% in patients without gastro-intestinal disease, but in those with liver cirrhosis or choledocholithiasis it was only 56% and 44%, respectively. In particular, cholestasis reduced specificity. Acute pancreatitis in its initial attack gave false-positive CA 19-9 values in 27% of cases, repeated bouts in chronic recurrent pancreatitis in as many as 50%. In chronic pancreatitis the specificity was 90%. Malignant tumours of pancreas and bile ducts were diagnosed with a sensitivity of 80%. Determination of CA 19-9 in pure pancreatic secretion failed to differentiate between the control group (30), chronic pancreatitis (21) and carcinoma of the pancreas (22).

Oregovomab

ViRexx Medical Corp is developing the murine monoclonal antibody oregovomab [OvaRex, MAb B43.13] for the treatment of ovarian cancer. Oregovomab targets the circulating tumour-associated antigen CA 125, which is shed from the surface of human ovarian cancer cells; the antibodies induce broad cellular and humoral immune responses against CA 125 via complex formation. Unlike free CA 125, CA 125-oregovomab complexes can prime dendritic cells, leading to downstream activation of T cells. The antibody is undergoing advanced clinical development. AltaRex, the originator of oregovomab, was acquired by, and merged into, ViRexx Medical Corp in December 2004. AltaRex (now ViRexx Medical Corp) has established several strategic corporate alliances for the development and/or commercialisation of oregovomab. Unither Pharmaceuticals, a subsidiary of United Therapeutics Corporation, entered into a licensing agreement with ViRexx in April 2002. The agreement covers most territories worldwide, except Europe and the Middle East, which are covered by other agreements (see below); ViRexx did retain the rights to most member nations of the EU and certain other countries. In August 2003, the agreement was extended, granting United Therapeutics Corporation development rights for Germany. AltaRex and Dompe entered into a distribution agreement for oregovomab in July 2004. Territories included in the agreement are Italy, Spain, Portugal, Hungary, Poland, Czech Republic, Switzerland, Austria and certain other Eastern European countries. Under the terms of the agreement, ViRexx retains responsibility for product development and registration of the antibody, upon commercialisation in the agreed territory. The two companies will work closely to achieve product registration throughout Europe. In June 2001, Dompe entered into a sublicensing agreement with FAES for the commercialisation of oregovomab in Spain and Portugal. ViRexx is also seeking collaboration partners for Northern European markets. Medison Pharma and AltaRex entered into an agreement in April 2002. Under the terms of the agreement, the two companies will establish a joint venture to market oregovomab in Israel and the Middle East. ViRexx also has an agreement with Genesis Pharma covering the commercialisation of the antibody in Greece, Turkey, Cyprus and the Balkans. Unither Pharmaceuticals has completed trial enrollment for its two pivotal phase III trials investigating oregovomab for the treatment of advanced ovarian cancer. In June 2006, Unither reached its enrollment goal of 177 patients for the IMPACT II study, the second of two identical double-blind, placebo-controlled trials. The IMPACT I study achieved its enrollment target in December 2005. Both IMPACT studies are designed to assess the effect of oregovomab on time to disease relapse in patients with advanced ovarian cancer (stage III/IV) who have achieved an optimal response with front-line chemotherapy, and are being conducted at over 60 sites across the US. Data from the studies are intended to support registration of the antibody in the US. ViRexx also plans to utilise results from the IMPACT studies to support regulatory filings in Europe and in other countries. In addition, a phase II trial is being conducted to evaluate two dosing regimens of adjunctive oregovomab plus platinum-based first-line chemotherapy in patients with advanced ovarian cancer. The enrollment target of 40 patients has been achieved; primary study analysis is anticipated to be completed by the end of 2006. Several phase II trials with oregovomab as monotherapy or in combination with other chemotherapeutics have been completed across the US and Canada. Clinical trials have also been conducted in the EU, but ViRexx has suspended such EU studies on the basis of commercial considerations. Oregovomab has orphan drug status for the treatment of ovarian cancer; designation was granted by the US and the EU in 1996 and 2002, respectively. In addition, the US FDA granted fast-track status to the antibody in 1998. AltaRex (now ViRexx Medical Corp) has been awarded the US patent covering the company's technology for administering a low dose of foreign antibody to patients expressing the CA 125 antigen. A second US patent has also been issued for oregovomab covering the technique of photoactivation using ultraviolet light to modify antibodies and enhance specific beneficial immune responses. Furthermore, AltaRex was granted a 'multi-epitopic' patent application covering oregovomab by the European Patent Office (EPO) in October 2003. The patent covers the company's technology of IV administration of a low-dose foreign antibody, such as oregovomab, to patients expressing the target tumour-associated antigen CA 125. The EPO's grant of the patent for the European Union enables intellectual property protection of oregovomab in the great majority of worldwide markets.

Persistent Unilocular Ovarian Cysts in a General Population of Postmenopausal Women

In Brief OBJECTIVE At present it is not well known whether some persistent unilocular ovarian cysts can develop into malignancy. The aim of this observational study was to define the management of postmenopausal women with persistent unilocular ovarian cysts less than 50 mm in diameter and with normal serum CA 125 levels. METHODS Retrospective data were obtained from 226 post-menopausal women (mean age 56.2 years, range 45–87) with unilocular ovarian cysts who were followed up for a 5-year period. Women were referred because of postmenopausal symptoms, abdominal discomfort, and postmenopausal bleeding. All women underwent pelvic examination, transvaginal ultrasonography, and serum CA 125 measurement. Tumor-associated antigen CA 125 and ovarian cyst diameter were assessed routinely. Surgery was offered according to clinical indications and women's wishes. RESULTS Ovarian cyst diameter and serum CA 125 levels did not change in 172 of 226 women (76.1%). Conversely, the remaining 54 women had an increase in cyst diameter, and six of those (11.1%) also had raised serum CA 125 levels. All women with suspicious ovarian pathology (n = 54) and 84 without ovarian pathology underwent surgical management. International Federation of Gynecology and Obstetrics stage IB well-differentiated serous cystoadenocarcinomas were diagnosed in two of 54 women (3.7%). Serum CA 125 levels were elevated in both cases. CONCLUSION These findings suggest that the majority of unilocular ovarian cysts with diameter less than 50 mm are benign and remain unchanged. These lesions can be managed expectantly when there is no increase in the ovarian cyst diameter and the serum CA 125 concentration is normal. In postmenopausal women, persistent unilocular ovarian cysts can be managed conservatively provided the diameter and serum CA 125 levels remain within the normal range.

P363 Clinical significance of elevated tumor-associated antigen CA 19-9 in a patient with acute hepatitis citomegalovirus-related: does it always imply malignancy?

P363 Clinical significance of elevated tumor-associated antigen CA 19-9 in a patient with acute hepatitis citomegalovirus-related: does it always imply malignancy?

Persistent unilocular ovarian cysts in a general population of postmenopausal women: is there a place for expectant management?

At present it is not well known whether some persistent unilocular ovarian cysts can develop into malignancy. The aim of this observational study was to define the management of postmenopausal women with persistent unilocular ovarian cysts less than 50 mm in diameter and with normal serum CA 125 levels. Retrospective data were obtained from 226 postmenopausal women (mean age 56.2 years, range 45-87) with unilocular ovarian cysts who were followed up for a 5-year period. Women were referred because of postmenopausal symptoms, abdominal discomfort, and postmenopausal bleeding. All women underwent pelvic examination, transvaginal ultrasonography, and serum CA 125 measurement. Tumor-associated antigen CA 125 and ovarian cyst diameter were assessed routinely. Surgery was offered according to clinical indications and women's wishes. Ovarian cyst diameter and serum CA 125 levels did not change in 172 of 226 women (76.1%). Conversely, the remaining 54 women had an increase in cyst diameter, and six of those (11.1%) also had raised serum CA 125 levels. All women with suspicious ovarian pathology (n=54) and 84 without ovarian pathology underwent surgical management. International Federation of Gynecology and Obstetrics stage IB well-differentiated serous cystoadenocarcinomas were diagnosed in two of 54 women (3.7%). Serum CA 125 levels were elevated in both cases. These findings suggest that the majority of unilocular ovarian cysts with diameter less than 50 mm are benign and remain unchanged. These lesions can be managed expectantly when there is no increase in the ovarian cyst diameter and the serum CA 125 concentration is normal.

Clinical outcome and tissue trauma after laparoscopic and abdominal hysterectomy: a randomized controlled study

To evaluate clinical outcome and tissue trauma after laparoscopic and abdominal hysterectomy. Fifty women scheduled for abdominal hysterectomy were randomized to undergo either laparoscopic (n = 25) or abdominal (n = 25) hysterectomy. Surgical characteristics, hospital stay, convalescence and complications were analyzed. Blood samples for assay of markers of tissue trauma (interleukin-6, C-reactive protein, tumor-associated trypsin inhibitor and tumor-associated antigen CA 125) were taken preoperatively, on the first, second and seventh postoperative day and at the follow-up visit four weeks after surgery. In uncomplicated hysterectomies (n = 18) the operating time (85.3 min versus 57.5 min, p < 0.00001) was longer for laparoscopic group but the hospital stay (2.1 days versus 3.4 days, p < 0.00001) and sick leave (21.4 days versus 38.5 days, p < 0.00001) were shorter in the laparoscopic group. Postoperative increases in all markers were significant in both groups. The interleukin-6 concentration was highest on the first postoperative day in both groups, that of C-reactive protein on the second postoperative day in both groups, tumor-associated trypsin inhibitor on the seventh postoperative day in the laparoscopic group and on the second postoperative day in the abdominal group and tumor-associated antigen CA 125 on the seventh postoperative day in both groups. Both interleukin-6 and C-reactive protein levels were lower in the laparoscopic group on the first (p = 0.01 and p = 0.03, respectively) and on the second postoperative day (p = 0.02 and p < 0.001, respectively) compared with the abdominal group. No differences were seen in tumor-associated trypsin inhibitor and tumor-associated antigen CA 125 levels between the groups. Laparoscopic hysterectomy should replace abdominal hysterectomy whenever possible because of a more favorable clinical outcome and less tissue trauma.

Biliary CA 19-9 values correlate with the risk of hepatic metastases in patients with adenocarcinoma of the pancreas

Serum values of the tumor-associated antigen CA 19-9 are useful as an independent predictor of survival in patients with adenocarcinoma of the pancreas. However, the utility of biliary CA 19-9 values is unknown. This study was undertaken to determine whether biliary CA 19-9 levels are predictive of hepatic metastases. Between 1991 and 1996, thirty-eight patients treated for adenocarcinoma of the pancreas were evaluated using a biliary CA 19-9 assay. Bile was obtained from percutaneous stents placed during the perioperative period. Five of the 38 patients had low serum levels of CA 19-9 (<2 U/ml) and were excluded from the study. Twenty-seven (80%) of the 33 patients developed distant metastases: five pulmonary, five peritoneal, and 17 hepatic. Liver metastases were discovered initially in 10 and after resection of the primary tumor in seven (median interval 10 months). Biliary CA 19-9 values were significantly higher in patients with hepatic metastases (median 267,400 U/ml; range 34,379 to 5,000,000 U/ml) compared to patients without metastatic disease (median 34,103 U/ml; range 6,620 to 239,880 U/ml; P <0.006). Patients with hepatic, peritoneal, and pulmonary metastases had median survivals of 8, 14, and 35 months, respectively ( P <0.0041). All patients without metastatic disease are alive (median follow-up 13 months). Biliary CA 19-9 values are associated with a stepwise increase in the risk of developing metastatic disease. Patients with biliary CA 19-9 levels greater than 149,490 U/ml have an increased risk of developing recurrent disease in the liver and may warrant further hepatic evaluation or therapy.

High coincidence of Mirizzi syndrome and gallbladder carcinoma

Background. Mirizzi syndrome is a rare complication of long-standing cholelithiasis. It is defined as obstructive jaundice caused by external compression of the common hepatic duct by an impacted stone in the gallbladder neck. Gallstone disease and cholelithiasis-associated chronic biliary inflammation may play a causative role in the pathogenesis of gallbladder carcinoma. The purpose of this study was to investigate the coincidence of gallbladder carcinoma associated with Mirizzi syndrome. Furthermore, the diagnostic value of elevated CA 19-9 levels as indicator for a coincidental gallbladder carcinoma in this syndrome was studied. Methods. Patient demographics, clinical findings, laboratory data, results of diagnostic studies, pathologic reports, and intraoperative findings of 1579 patients undergoing cholecystectomy were obtained from patient records and were retrospectively studied. Only patients with proven Mirizzi syndrome (i.e., extrinsic mechanical compression of the common hepatic duct by impacted gallstones, associated chronic cholecystitis, and a history of jaundice) were included in this study. Results. Eighteen cases of Mirizzi syndrome (1.0%) out of 1759 cholecystectomies performed between January 1986 and March 1995 were identified. The seven male patients and 11 female patients had an average age of 74.8 years (range, 32 to 87 years). In five of these patients (27.8%) coincidental cases of gallbladder carcinoma were detected. The incidence of unsuspected malignancies in long-standing gallstone disease was 36 (2%) of 1759 and was statistically significantly different (p < 0.001) from the incidence in patients with Mirizzi syndrome (27.8%, 5 of 18). No significant difference was noted in age, gender, duration of jaundice, and type of lesions between these two groups. Tumor-associated antigen CA 19-9 level was elevated in 12 patients with Mirizzi syndrome, but it was significantly higher (p < 0.0001) in all five patients with coincidental gallbladder neoplasm and peaked at 1000 units/ml. All patients diagnosed with gallbladder carcinoma died within 18 months after operation. Conclusions. There is high association of gallbladder cancer in Mirizzi syndrome. Elevated CA 19-9 levels in this syndrome are indicative of a coincidental gallbladder malignancy. Because of this high coincidence of Mirizzi syndrome and gallbladder cancer we recommend an intraoperative frozen section of the gallbladder in all patients presenting with Mirizzi syndrome.

Effects of Irradiation on the Expression of Surface Antigens in Human Ovarian Cancer

Tumor cells from four established human ovarian carcinoma cell lines were analyzed for their expression of surface antigens including MHC Class I, Class II, ICAM-1, and the tumor-associated antigens CA 125 and Her2-neu before and after exposure to high doses of gamma irradiation. All four ovarian cell lines expressed variable levels of MHC Class I and Her2-neu. ICAM-1 antigens were expressed in only two cell lines and Class II and CA 125 surface antigens were absent in all the cell lines evaluated. Exposure to high doses of gamma irradiation (i.e., 5000 to 10,000 cGy) significantly and consistently increased the expression of all surface antigens present on the cells prior to irradiation. Importantly, the irradiation-induced upregulation was persistent and lasted until all the cells died. Irradiation was unable to induce neoexpression of antigens previously not expressed by the cells (i.e., MHC Class II or ICAM-1). These findings may partially explain the increased immunogenicity of tumor cells following irradiation and may suggest enhanced immune recognition in tumor tissue in patients receiving radiation therapy.

A monoclonal antiidiotypic antibody ACA 125 mimicking the tumor-associated antigen CA 125 for immunotherapy of ovarian cancer.

A new concept of oncological immunotherapy comprises the attempt to trigger the immune system of the host into a response against tumor cells. Antiidiotypic antibodies bearing the internal image of an antigen expressed on the surface of the tumor seem to be most suited for this purpose. We have generated a murine antiidiotypic antibody (ACA 125) functionally imitating the tumor-associated antigen CA 125, which can be detected in about 80% of ovarian carcinomas. The hybridoma cell was adapted to serum-free medium and antibody was produced in a hollow fiber cell culture system (Technomouse). ACA 125 (Ab2) shows high affinity for the paratope of Ab1 (affinity constant: 2.3 x 10(9) liters/mol) and binding of Ab2 to Ab1 is completely inhibited by the nominal antigen. Application of F(ab')2 fragments of ACA 125 to rats lead to an anti-CA 125 immunity by production of IgG and IgM antiantiidiotypic antibodies (Ab3) that bind to both ACA 125 and CA 125. Furthermore the induction of a non-MHC-restricted cell-mediated cytotoxicity for human ovarian adenocarcinoma cell line NIH-OVCAR3 (expressing CA 125 on its surface) could be proved; additionally complement-dependent cytotoxicity (CDC) as well as an antibody-dependent cellular cytotoxicity (ADCC) was observed. Thus, monoclonal antiidiotypic antibody ACA 125 fulfills recent criteria for an antibody, which might be successful in immunotherapy using the anti-idiotypic network approach.

The patterns of coexpression of tumor-associated antigens CA 19-9, TAG-72, and DU-PAN-2 in human pancreatic cancer

Coexpression of CA 19-9, DU-PAN-2, and TAG-72 was examined by a multilabeling immunohistochemical procedure in 31 surgically resected human pancreatic carcinomas. CA 19-9 was expressed in 74%, DU-PAN-2 in 84%, and TAG-72 in 65% of the cases. CA 19-9 and DU-PAN-2 were coexpressed in 16 cases (52%), CA 19-9 and TAG-72 in 10 cases (32%), DU-PAN-2 and TAG-72 in 8 cases (26%), and all three antigens in 10 tumors (32%). With the combination of the three antibodies, all 31 tumors were labeled. However, heterogeneity in antigen expression existed and the antibodies against CA 19-9, DU-PAN-2, and TAG-72 depicted 55%, 49%, and 35% of the tumor cells, respectively. The average number of cells coexpressing CA 19-9 and DU-PAN-2, CA 19-9 and TAG-72, DU-PAN-2, and TAG-72 was 22%, 11%, and 10%, respectively. Only about 3% of tumor cells coexpressed all three antigens, whereas 8% of tumor cells did not express any of the antigens. There was no correlation between the patterns of antigen expression and age or sex. However, there was a tendency of reduced CA 19-9, DU-PAN-2, and TAG-72 expression in less differentiated tumor areas. The results show that: 1) pancreatic cancer cells coexpress two or three antigens in different proportions; and 2) although the sensitivity for pancreatic cancer reaches 100% by all three antibodies, a remarkable heterogeneity exists and a minor fraction of tumor cells does not seem to produce any of these antigens.

Immunocytochemical and serological expression of CA 125: a clinicopathological study of 40 malignant ovarian epithelial tumours.

Elevated serum levels of the tumour-associated antigen CA 125 occur in more than 80% of cases of ovarian carcinoma. The antigen can be demonstrated in formalin-fixed tissue using the monoclonal antibody OC 125, which localizes it to the surface membrane or cytoplasm. This study was performed to determine the relationship between pre-operative serum levels of CA 125 and the subsequent immunocytochemical findings in the surgical specimen. Paraffin-wax embedded sections from 40 consecutive borderline and frankly malignant ovarian epithelial tumours were stained with OC 125. The pattern and distribution of immunostaining were investigated in relation to histological appearances. Serous tumours showed a 100% correlation between immunocytochemical findings and elevated serum levels of CA 125. Amongst the other histological types, correlation was less good; mucinous tumours and undifferentiated carcinomas showed a poor correlation. Immunostaining within tumours was heterogeneous and only loosely related to morphological appearances. Our finding suggests that, with the exception of serous tumours, immunolocalization of CA 125 is insufficiently sensitive to provide reliable clinical guidance to the likely value of serum CA 125 monitoring on follow-up.

Differential diagnosis of ovarian cancer with tumour markers CA 125, CA 15‐3 and TAG 72.3

To determine the accuracy of tumour associated antigens CA 125, CA 15-3 and TAG 72.3 in the differential diagnosis of benign and malignant pelvic masses and to compare the results with a previously defined risk of malignancy index (RMI). Retrospective analysis of samples collected during a prospective observational study. Department of Obstetrics and Gynaecology, the Royal London Hospital and Duke University Medical Center. One hundred and forty-three consecutive patients undergoing surgery for an adnexal mass. Tumour marker levels were determined by radio-immunoassay in stored serum samples obtained from 143 study subjects. The highest diagnostic accuracy of the tumour marker panel was achieved by defining a positive result as elevation of any two of CA 125 (> 30 u/ml), CA 15-3 (> 30 u/ml) and TAG 72.3 (> 10 u/ml), (sensitivity 66.7%, specificity 93.1%). Similar diagnostic accuracy could be achieved by CA 125 alone using an upper limit of 50 u/ml (sensitivity 66.7%, specificity 94.1%). Inclusion of CA 15-3 or TAG 72.3 in stepwise logistic regression analysis did not improve the discriminative performance of the RMI. The risk of malignancy index incorporating CA 125, menopausal status and ultrasound is superior to the panel of three tumour markers for pre-operative differential diagnosis of the pelvic mass.

Elevated serum CA 19-9 levels in hepatobiliary cystadenoma with mesenchymal stroma. Two case reports with immunohistochemical confirmation

Hepatobiliary cystadenomas with mesenchymal stroma (CMS) are rare tumors. Two cases are reported that illustrate many features of CMS, including polypoid involvement of the common hepatic duct in one case. Both tumors were associated with elevated serum levels of the tumor-associated antigen CA 19-9 but normal levels of carcinoembryonic antigen and alpha-fetoprotein. Immunohistochemical analysis confirmed the presence of CA 19-9 in the epithelial component of the tumor. The implications of these findings are discussed, both in relation to the histogenesis of CMS and its preoperative diagnosis. A minimally elevated level of CA 19-9 was found in only one of five patients with hydatid disease of the liver, an important differential diagnosis in clinical management.

The use of porcine liver (2 → 3)-α-sialyltransferase in the large-scale synthesis of α-Neu p5Ac-(2 → 3)-β- d-Gal p-(1 → 3)- d-Glc pNAc, the epitope of the tumor-associated carbohydrate antigen CA 50

α-Neu p5Ac-(2 » 3)-β- d-Gal p(1 » 3)- d-Glc pNAc ( 2) and, α-Neu p5Ac-(2 » 3)-β- d-Gal p-(1 » 3)-β- d- Glc pNAcOMBn were prepared on a large scale by the action of β- d-Gal pNAC (2 » 3)α-sialyltransferase (partially purified from porcine liver) on β- d-Gal p-(1 » 3)- d-Glc pNAc and β- dGal p (1 » 3)-β- d-Glc pNAcOMBn, respectively. The trisaccharide 2 is the epitope of the tumor-associated carbohydrate antigen CA 50, highly expressed in human pancreatic adenocarcinoma.

Effect of differentiation agents on expression of CA 125, alkaline phosphatase, and cytokeratins in human ovarian adenocarcinoma cells (OVCA 433)

A number of chemical agents have been found to influence the proliferation, morphology, enzymatic activity, and antigen expression of neoplastic cells toward a more differentiated pheno-type. We studied the effects of differentiating agents retinoic acid, sodium butyrate, and dibutyryl cyclic AMP on the expression of the tumor-associated antigen CA 125 and several biochemical markers of differentiation in cultured OVCA 433 ovarian cancer cells. Treatment of OVCA 433 cells with these agents for 96 hr reduced cellular proliferation and altered cellular morphology. Quantitation of cell surface CA 125 using flow cytometry revealed that CA 125 expression was reduced by 35–50%. The amount of CA 125 antigen shed into the culture media was reduced to a similar degree. In addition, differentiation inducers markedly enhanced cellular alkaline phosphatase activity and induced the expression of a 65–67-kDa cytokeratin. These findings provide support for the induction of a more differentiated phenotype by these agents.

The value of the tumor marker CA 15-3 in diagnosing and monitoring breast cancer. A comparative study with carcinoembryonic antigen

To estimate the utility of the tumor-associated antigen CA 15-3 in the diagnosis of patients with breast cancer, this tumor marker was measured preoperatively in 1342 patients. This group included 509 patients with malignant disease (134 breast cancer patients and 375 patients with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast and 738 patients with other benign diseases). The results were compared with those obtained for carcinoembryonic antigen (CEA) in the diagnosis of breast cancer. The CA 15-3 level was above normal (25 U/ml) in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. The CEA level was elevated in 26% of patients with breast cancer (more than 3 ng/ml). There was a good correlation of CA 15-3 levels with the tumor stage of breast cancer. Both CA 15-3 and CEA also were determined in 671 patients who had received initial curative surgery of breast cancer and who regularly attended our follow-up clinic. The CA 15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the postcare period, carcinoma recurred in 205 patients. Of these, 73% had CA 15-3 concentrations above 25 U/ml; only 50% had CEA values above 3 ng/ml (P less than 0.0001). Although neither CA 15-3 nor CEA were sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 was significantly better than CEA in the detection of breast cancer metastases.