[CANCER RESEARCH 43, 4491-4496, September 1983]

Clinical Value of Serum Glycoprotein Galactosyltransferase Levels inDifferent Histológica! Types of Ovarian Carcinoma1

Pascal Gauduchon, Catherine Tillier, Christine Guyonnet,2 Jean-François Heron, Edith Bar-Guilloux, andJean-Yves Le Talaer3

Service de Biochimie Clinique et Expérimentale[C. G., C. T., J-Y. L.¡and Service de Médecine[J-F. H.] du Centre FrançoisBadesse (Centre Régionalde Lutte contre le

Cancer), Laboratoire de Biochimie et de Toxicologie de la Facultéde Pharmacie, Universitéde Caen [P. G.], and Laboratoire de Biochimie de la Facultéde Pharmacie,UniversitéRenéDescartes [E. B-G.¡,Paris, France

ABSTRACT

Serum glycoprotein galactosyltransferase levels were determined in 28 healthy women and 113 patients with ovariancarcinoma with various histological types, at different clinicalstages. Ovomucoid, which possesses terminal A/-acetylglucosa-

minyl residues, was used as glycoprotein acceptor. Clinical correlations between galactosyltransferase levels and tumor burdenwere examined, as well as the variations due to histology. Follow-

up studies could be done for 60 patients, and correlations withclinical evolution, established. Galactosyltransferase might be apromising marker for the diagnosis and follow-up of ovarian

carcinomas.

INTRODUCTION

Important changes in cell surface glycoconjugates have beendescribed in malignant diseases (13, 26, 28). Synthesis of thecarbohydrate moieties of those molecules is achieved by glyco-syltransferases of various specificities. In general, these aremembrane-bound enzymes, but soluble forms have also been

found in human physiological fluids (14,15, 20).Altered glycosyltransferase activities in malignant cells and

tissues (5, 10, 30), as well as in sera of cancer patients (1, 9),have been reported. In earlier publications (16, 29), levels ofserum GT4 [UDP-galactose:/V-acetylglucosaminyl-glycoprotein

GT (EC 2.4.1.38)] in some patients with various types of cancerwere elevated compared to those of healthy controls, althoughin many cases such an increase was not observed (29); on theother hand, other pathologies, especially liver diseases, also ledto elevated serum GT levels (16). However, a GT isoenzymewhich might be tumor-specific was characterized (22, 23, 25).

Bhattacharya ef a/. (4) observed that total GT level was significantly elevated in the sera of ovarian cancer patients as compared to normal controls. The levels of the enzyme appeared tocorrelate well with tumor volume and clinical status of the patient,although discrepancies were observed in a few cases (6-8).

Since these papers concerned only small numbers of patients,more data were still needed in order to assess the practicalusefulness of this biological marker in ovarian carcinoma. Thus,serum GT levels were tested in 113 patients and 28 healthy

' This work was supported by the Ugue Nationale Françaisecontre te Cancer,

the FédérationNationale des Centres de Lutte contre le Cancer, and théLigueDépartementale Française(Calvados) contre le Cancer.

2 Recipient of a grant from the Ligue Nationale contre le Cancer, France.3To whom requests for reprints should be addressed, at: Centre François

Badesse, Route de Lion sur Mer, 14021 Caen Cedex, France.* The abbreviations used are: GT, galactosyltransferase; SGF, fetuin lacking

terminal sialic acid and penultimate galactose residues.Received May 27,1982; accepted June 10,1983.

women. Correlation between serum levels of this enzyme andclinical status was examined for each histological type. Furthermore, for 60 patients, serum GT levels were serially determinedduring therapy.

MATERIALS AND METHODS

Materials. UDP-[3H]galactose (13.1 Ci/mmol) was obtained from the

Radiochemical Centre, Amersham, England. Unlabeled UDP-galactose,

ovomucoid, and sodium cacodylate were obtained from Sigma ChemicalCo. Other chemicals were purchased from Merck.

Collection of Serum Samples. Blood was collected by venipuncturein 10-ml B-D Vacutainer tubes without anticoagulant. After centrifugation

to remove blood cells, the serum samples were used immediately orstored frozen at -20° until assay. Control subjects were 28 female

laboratory workers from our Cancer Institute. Pathological blood sampleswere drawn from 113 patients with ovarian carcinoma. Some of thepatients were in complete clinical remission for 2 to 10 years. Most,however, were included in the study directly after initial surgery, onreferral to our Cancer Institute for complementary treatment. Finally, asmall number were new patients who had not yet received treatmentprior to inclusion in the investigation. In our therapeutic protocol afterinitial surgery, Stage I patients [according to International Federation ofGynecology and Obstetrics staging (complete surgery for postmeno-

pausal women, including omentectomy and lomboaortic node biopsies)]received no further treatment; Stage II patients received pelvic radiotherapy; and Stages III and IV patients received various monthly coursesof chemotherapy. Whenever possible, "second-look" surgery was per

formed on Stages III and IV patients 6 to 8 months after the firstoperation. Tumor volume was also evaluated clinically with ultrasonicand radiological examinations when necessary. Choice of treatment wasin no way influenced by the results of the serum GT assay, since thesewere obtained quite some time after the samples had been taken.Histological classification was according to WHO criteria. For 60 patientsreceiving regular chemotherapy, serial serum GT tests were performed,since blood samples could be taken just before drug infusions.

Assay of GT. Serum GT activity was assayed according to the methoddescribed by Podolsky and Weiser (23). However, ovomucoid was usedinstead of asialoagalactofetuin (SGF) as glycoprotein acceptor. Ovomucoid has A/-acetylglucosaminyl residues in a nonreductive terminal posi

tion (18). The assay mixture contained 10 M! of serum and 2 mg ofovomucoid in a final volume of 150 /¿I.Final concentrations of the otherchemicals were: 26 rriM sodium cacodylate, pH 7.2; 50 mw sodiumchloride; 20 mw manganese chloride; and UDP-[3H]galactose, 0.075 ITIM,

with a specific activity of 0.23 Ci/mmol.An assay mixture without UDP-[3H]galactose was first preincubated

at 37°for 30 min. The reaction was then started by adding the UDP-[3H]galactose solution. The reaction was stopped by adding 1 ml of 5%

phosphotungstic acid in 2 N HCI. The precipitate was collected on aWhatman GF/A filter. The filter was washed several times with phosphotungstic acid and cold ethanol. Radioactivity precipitated on the filterwas counted using 10 ml of Biofluor scintillator (New England Nuclear),with a counting efficiency of 35%. Radioactivity obtained by stopping

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P. Gauduchon et al.

the reaction at 0 min was subtracted from the total radioactivity. Theresults were expressed as units of GT per ml of serum, whereby oneunit of GT is the amount of enzyme which transfers one nmol [3H]-

galactose to the acceptor during a 60-min incubation period. Enzyme

assays were carried out in duplicate on each serum sample; the meanof those values was used in "Results." In our experimental conditions, a

linear kinetic of incorporation was observed for at least 2 hr. UDP-

galactose and acceptor saturation were effective. Virtually no incorporation of galactose occurred when the acceptor was deleted. Manganousion was an absolute requirement, and an optimal Mn2* concentrationwas used in the assay.5

RESULTS

GT Activities in Normal and Cancer Subjects

Values of serum GT activities from 28 normal control womenranged from 5.6 to 11.9 units/ml with a mean value at 9 ±3units/ml (mean ±2 S.D.). Thus, a value of over 12 units/ml wasconsidered as abnormal (Chart 1). One of our control subjects,a 23-year-old woman, had an elevated serum GT activity when

first assayed; she subsequently received surgery for a benignserous ovarian cyst, and her serum GT returned to normal.Thirty-six of the 113 patients had abnormal serum GT levels at

the beginning of the study (Chart 1). The highest values wereobserved in patients presenting large peritoneal masses, asciticor pleural effusion, or hepatic métastases. For 4 patients, weobserved a dramatic drop of the serum GT level after evacuationof the effusion: in these cases, GT levels in ascitic fluids werevery high. On the other hand, almost all of the disease-free

patients (49 of 54) had serum GT values within the normal range.In order to correlate serum GT activities with the estimated

tumor volume, patients were first grouped according to histology,and then divided further into 3 subgroups: untreated tumor-bearing patients (no surgery), treated tumor-bearing patients,and clinically or surgically proven disease-free patients. Results

of this study are provided in Chart 2. All but 2 of the 15 untreatedpatients exhibited abnormal values. The values of treated tumor-

bearing patients varied. Patients with serous adenocarcinomafrequently had abnormal values, although these were generallylower than those observed for the untreated patients with thesame histology. Nine of the 10 patients with mucinous adenocarcinoma were within the normal range, in contrast to the highlevels observed for the 3 untreated patients with the samehistology. Seven patients were classified as having borderlinetumors (3 serous type; 4 mucinous type); all but one had normalGT correlating with the absence of any residual tumor at thetime of the assay. Eighteen patients had other histological typesof ovarian malignant tumors. Among the 9 patients with germcell tumors, only one was clinically exhibiting tumor; her GTactivity was 18.8 units. The other 8 were clinically free of disease.Two of them had subnormal GT values; in one case, the assayhad been done only 10 days after reductive surgery, and the GTlevel returned to normal in the subsequent assays. The 4 patientswith undifferentiated histology had normal values, although oneof them was still bearing tumor. Three of 4 patients with granulosa cell tumors were clinically free of disease; the other hadmetastasis to the liver, and her GT level was very high. A normalGT value was found for one patient bearing a mesonephroid

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5C. Guyonnet, P. Gauduchon, E. Bar, C. Tillier, J. F. Heron, and J-Y. Le Talaer,

Analytical studies on human serum glycoprotein:galactosyltransferase, manuscriptin preparation.

n - 28 59 »

Chart 1. GT activity in the sera of normal subjects and ovarian cancer patients;n, number of cases in each group; i£, range between the mean ±2 S.D. of thecontrol group.

tumor. Finally, for 5 patients, obvious ovarian malignant tumorwas present, although histologies were unknown; 3 of them hadhigh GT values.

Serial Determinations

Patients with Clinical Evidence of Disease (34 Cases). For11 of the 13 new patients whose initial values had been abnormal, a striking drop of serum GT was observed in correlationwith a significant clinical improvement due to the first courses ofchemotherapy, as shown in Chart 3 (the other 2 patients diedsoon after the first treatment).

A good correlation between GT levels and clinical course wasobserved, during prolonged follow-up studies, for 18 of 34 pa

tients. In 15 cases, the decrease of serum GT correlated withpartial or complete clinical remission; when relapse occurred (10of those patients), serum GT rose simultaneously. For the other3 patients, high serum GT correlated with permanent clinicalevidence of disease. For example, Chart 4 (Patient A. L.) showsa dramatic fall of serum GT after one course of chemotherapy,corresponding to the almost complete disappearance of 2 largepelvic masses. Six months later, there was no clinical evidenceof tumor, although small disseminated peritoneal masses werefound at second-look laparotomy. Chart 4 shows this same

correlation between serum GT alterations and clinical course for2 cases of papillary serous adenocarcinoma (Patients O. R. andM. I.).

A delayed response was observed for 5 of 34 patients withclinical evidence of disease: the rise in serum GT appeared onlyafter clinical changes had occurred, and at a time when therewere no longer any gross clinical changes. For instance, PatientT. L. (Chart 5), who was irradiated 1 year before inclusion in thestudy, exhibited stable serum GT values despite recurrence ofdisease; a rise in levels was only observed during the last 4months prior to death. The same phenomenon was observed for

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GTin Ovarian Carcinoma

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22 22 10 10 20Chart 2. GT activity in the sera of cancer patients, according to clinical status and histology; B. same as in Chart 1; "other" histologies are: A, germ cell; •,borderline;

I, undifferentiated; *, granulosa cell; T, mesonephroid; *, unknown. TBP, tumor-bearing patients; CR, complete clinical remissions; UT, untreated; 7",under treatment.

Charta Effect of the first chemotherapy courses on serum GT activity./.beforeany treatment; //, 1 to 2.5 months after the first chemotherapy course. Ü,sameas in Chart 1.

Patient F. F. (Chart 5), whose clinical status remained relativelystable, under low dosages of Alkeran, although there was clinicalevidence of tumor. Her serum GT levels rose slightly without anyclear correlation with the course of the disease. Further documentation is needed to determine whether or not a sudden risecorrelates with terminal development, as was recently observedat our Center.

No correlation was found for 11 of the 34 patients with clinicalevidence of disease; serum GT tests were of no clinical utility,since their values remained within the normal range, whether thepatient entered in clinical remission or relapsed. For instance,

Patient D. R. (Chart 6) was in clinical remission from serousadenocarcinoma when she entered the study; this remission wasconfirmed by second-look laparotomy; however, when local relapse occurred, terminating in massive ascitis, no modification ofserum GT was observed. When Patient M. J. C. (Chart 6)enteredthe study, her serum GT level was normal, despite relapsingStage III serous adenocarcinoma. Serum GT values continuedto remain within normal range even after complete remissionwas obtained under chemotherapy. Patient S. L. (Chart 6), whoserecurrent mucinous adenocarcinoma failed to respond to treatment, followed her entire terminal course without exhibiting anychange in serum GT levels. Similarly, the Stage III endometrioidadenocarcinoma of Patient M. C. (Chart 6) followed a slow localdevelopment, while her serum GT remained slightly subnormal.

Patients in Complete Remission. Twenty-six patients hadcomplete response to therapy and continued to be clinically freeof disease during our study. Nineteenof them always had normalGT values. One of the remaning 7 patients, T. L., was incomplete clinical remission under chemotherapy, with normalvalues of GT for 8 months after entering the study. Then sherefused the second-look laparotomy and any further treatment.She came back to our institution 3 months later with severe renalinsufficiency. At that time, serum GT was 30.7 units/ml. Shesuccumbed to her renal disease shortly thereafter, without anyclinical evidence of relapse. Only her autopsy revealed a smallcancerous mediastinal node without any other tumor site. PatientG. M. (Chart 7) also suffered from renal insufficiency and hearingproblems due to cisplatin toxicity, which improved slightly aftercessation of this drug. Second-look surgery did not show anytumor, and she remains well, although her serum GT rose for 5months, during which time there was no evidence of disease,

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20

D D O O D O O O

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Chart 4. Serial determination of GT activity in sera of ovarian cancer patients.B, same as in Chart 1. Cfi, clinical remission; LE. local evolution; M. evidence ofmétastases;¿,first surgical operation; [[. second-look operation; D, chemotherapy

and then returned to normal. The same elevation of valueswithout clinical changes was observed for 3 other patients.Patient F. L. (Chart 7), with a Stage IV endometrioid carcinoma,responded dramatically to chemotherapy, with a complete surgically proven remission. Her serum GT levels were still slightlyelevated, although she was perfectly well until a recent herpeszoster. The last patient recently showed progressive increase ofher serum GT, up to 30 units, and lomboaortic pains suggestinga relapse. Careful surveillance of these patients for possiblerecurrent disease might help shed light on the significance of theserum GT alterations.

DISCUSSION

White there is a general need for tumor markers in the management of malignant disease, this is particularly true for ovariancarcinoma, since the clinical course of this disease is usuallyoccult. Clinicians often have difficulty in assessing response totreatment, and especially in predicting early relapse. Althoughfor other cancer types, in situ assays of tumor markers have

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Chart 5. Serial determination of GT activity in sera of ovarian cancer patients.For details, see legend of Chart 4.

been proven to be of great interest in clinical practice, generally,a tumor marker is most useful when present in biological fluids,and when it correlates with tumor burden, allowing a clinicalmonitoring of the disease.

First described by Bhattacharya ef a/. (4), serum GT might bejust such a marker. We were able to confirm their results byfollowing the serum GT levels of 113 patients with various typesof ovarian carcinoma.

These authors used asialoagalactofetuin (SGF) as an acceptor.SGF bears both N-acetylglucosaminyl- and W-acetylgalactosa-minyl-terminal residues (2). Thus, when using SGF as acceptor,

at least 2 different enzyme activities are determined simultaneously: UDP-galactose:A/-acetylgalactosaminylglycoprotein-^-3-galactosyltransferase ("mutin-type" GT); and UDP-galactose:W-

acetylglucosaminylglycoprotein-/3-4-galactosyltransferase. The

former generally appears to be low in normal human serum (2,15); it is present in various tissues; however, in human colonadenocarcinoma extracts (12) and in human lung adenocarci-

noma homogenates (11), no significant increase of GT activitieswere found using mutin as acceptor, as compared with normaltissues. The other enzyme activity, which can be assayed withSGF, can be measured with ovomucoid as acceptor. Saccharidicchains of ovomucoid bear many terminal W-acetylglucosaminyland no A/-acetylgalactosaminyl residues (21) and need no pre

vious desialylation and degalactosylation. In this respect, usingovomucoid as acceptor appears to be more defined, althoughassaying the other activities might also be clinically useful.

We found that serum GT showed lower V™»and Km forovomucoid as compared to SGF. Thus, normal values usingovomucoid and expressed as nmol of galactose transferred/ml/60 min are lower than those obtained by us and others usingSGF. This might be due to differences in the structure of the N-

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GT in Ovarian Carcinoma

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Chart6. SerialdeterminationofGTactivityinseraofovariancancerpatients.Fordetails,seelegendofChart4.

glycosidically linked glycans of ovomucoid and SGF.Serum GT levels satisfactorily reflected the clinical status of

the patient for 81 of 113 patients (72%) in the general study.Five false-positives and 27 false-negatives were observed. Prolonged follow-up studies (60 patients) showed, however, thatthe true clinical usefulness of total serum GT might be lower,since 37 patients would have been correctly classified with thisassay (62%) to be compared with 7 false-positives and 16 false-negatives (38% misclassified). Five of these 16 patients had anincrease in their serum GT later with disease evolution (delayedresponse).The increase of serum GT could have been predictive

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Chart 7. Serial determination of GT activity in sera of ovarian cancer patients.For details, see legend of Chart 4.

of relapse in 6 of 18 cases. Whether the false-positive patientsare in occult evolution, although still in clinical remission, canonly be demonstrated by continuing follow-up (becoming predictive rises). Although 14 of 23 patients with serous adenocarci-noma and only 3 of 9 patients with mucinous adenocaränomaswere correctly classified, the number of patients is too low toaffirm that the observed difference is significant.

Other diseases might interfere with serum GT determinationand explain some of the transient variations we observed inpatients in clinical remission. For instance, renal insufficiency,inflammation, or hepatic dysfunction might influence the resultseither by increasing normal serum GT production by lowering itsdegradation or possibly reducing elimination, or by modifying theisoenzyme pattern. On the other hand, specific activators orinhibitors, or endogenous acceptors might appear in the serumduring these pathologies (24). Thus, further studies are needed,and are in fact underway, to clarify the influenceof those differentparameters. Obviously, total serum GT activity does not systematically reflect the tumor burden of the patient.

Chatterjee et al. (6) also occasionally observed false-negativesin their studies. Other markers might prove useful in these false-negatives. For almost every tumor-bearing patient with mucinousadenocarcinoma, we observed an abnormal elevation of carci-noembryonic antigen which generally reflected the clinical evolution. In a parallel study, we measured the placenta-likealkalinephosphatase isoenzyme with the specific thermal denaturationtechnique described by Moss ef al. (19). We observed a pathological elevation of this isoenzyme in a few tumor-bearing patients including some with normal GT values.6However, a more

* Theseresultswillbepublishedelsewhere.

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accurate evaluation of placenta-like alkaline phosphatase isoen-

zyme as an ovaríantumor marker might be soon possible withthe recently published more specific and sensitive immunoassays(17). Other potential markers have been described recently, suchas ovarian isoamylase (27) and /3-hexosaminidase (3).

Simultaneous investigations of these various markers, in closecorrelation with clinical course and histological type, will allow asatisfactory evaluation of each of them and hopefully lead to achoice combination of biochemical markers for the clinical management of ovarian carcinoma.

ACKNOWLEDGMENTS

This work is dedicated to C. Guyonnet. whose youthful enthusiasm for researchwas cut short by her untimely death last June.

The authors gratefully acknowledge the clinical staff of the gynecological unitfor allowing us access to their patient charts, and our colleagues of the pathologyunit, nurses, and technicians for their assistance.

We thank P. Guiltet, Y. Verbauwhede, and J. Mauduit for their help duringpreparation of the manuscript, and M. Aubert for her technical assistance.

We thank Dr. J. S. Abbatucci, director of our Cancer Institute, for his encouragement and support.

REFERENCES

1. Bauer, C. H., Reutter, W. G . Erhart. K. P., Kottgen. F., and Gerok. W.Decrease of human serum fucosyltransferase as an indicator of successfultumor therapy. Science (Wash. D. C.), 201:1232-1233,1978.

2. Berger, E. G., Kozdrowski, I., Weiser, M. M., Van Der Eijnden, D. M., andSchiphorst, W. E. C. M. Human serum galactosyltransferase: distinction,Separation and product identification of two galactosyltransferase activities.Eur. J. Biochem., 90: 213-222,1978.

3. Bhattacharya, M., and Barlow. J. J. Tumor markers for ovarian cancer. Int.Adv. Surg. Oncol., 2:155-176,1979.

4. Bhattacharya, M.. Chatterjee, S. K., and Barlow. J. J. Undine S'-diphosphate-

galactose:giycoprotem galactosyltransferase activity in the ovarian cancerpatient. Cancer Res., 36. 2096-2102,1976.

5. Bosmann. H. B., and Hall, T. C. Enzyme activity in invasive tumors of humanbreast and colon. Proc. Nati. Acad. Sei. U. S. A., 71:1833-1837,1974.

6. Chatterjee, S. K., Bhattacharya, M., and Barlow. J. J. Correlation of UDP-

galactose glycoprotein:galactosyltransferase levels in the sera with the clinicalstatus of ovarian cancer patients. Cancer Lett., 5: 239-244,1978.

7. Chatterjee, S. K., Bhattacharya, M., and Barlow, J. J. Glycosyltransferase andgiycosidase activities in ovarian cancer patients. Cancer Res., 39:1943-1951,

1979.8. Chatterjee, S. K., Bhattacharya, M., and Barlow, J. J. Determination of serum

galactosyltransferase levels in ovarian cancer patients for the evaluation of theeffectiveness of therapeutic programs. Cancer Lett., 8:247-253,1980.

9. Kessel, D., and Allen, J. Elevated plasma sialyltransferase in the cancer patient.Cancer Res.. 35: 670-672,1975.

10. Kessel, D., Sykes, E., and Henderson, M. Glycosyltransferase levels in tumorsmetastatic to liver and in unmvolved liver tissue. J. Nati. Cancer Inst., 59: 29-

32,1977.

11. Kijimoto-Ochiai, S., Makita, A., Kameya, T., Kodama, T., E., Araki, and Yoney-ama, T. Elevation of glycoprotein galactosyltransferase activity in human lungcancer related to histological types. Cancer Res., 41:2931-2935,1981.

12. Kim, Y. S., and Isaacs, R. Glycoprotein metabolism in inflammatory andneoplastic diseases of the human colon. Cancer Res., 35:2092-2097,1975.

13. Kim, Y. S., Isaacs, R., and Perdomo, J. M. Alterations of membrane glycopep-tides in human colonie adenocarcmoma. Proc. Nati. Acad. Soi. U. S. A., 714869-4873.1973.

14. Kim, Y. S., Perdomo, J., Bella, A., and Nordberg. J. Properties of CMP-W-acetylneuraminic acid:glycoprotein sialyltransferase in human serum and eryth-rocyte membranes. Biochim, Biophys. Acta, 244: 505-512,1971.

15. Kim, Y. S., Perdomo, J., and Whitehead, J. S. Glycosyltransferase in humanblood. I. Galactosyltransferase in human serum and erythrocyte membrane. J.Clin. Invest., 57: 2024-2032,1972.

16. Kim, Y. S., Perdomo, J., Whitehead, J. S., and Cortis, K. L. Glycosyltransferasein human blood. II. Study of serum galactosyltransferase and W-acetylgalactosaminyltransferase in patients with liver diseases. J. Clin. Invest,57: 2033-2039,1972.

17. Millan.J. L., and Stigbrand.T. Sandwichenzymeimmunoassayfor placentalalkalinephosphatase.Clin.Chem.,27:2014-2018,1981.

18. Morel. E,, Spik. G., and Montreuil.J. Mise en evidenced'une activitéglycopro-

téine:galactosyltransfèrasedanslesfluidesascitiqueset lesserumsde sourisporteusesde la tumeurYC8, C. R. Acad.Set.(Paris),282. 317-320,1976.

19. Moss, D. W., Shakespeare, M. J., and Thomas, D. M. Observations on théheat-stability of alkaline phosphatase isoenzyme in serum. Clin. Chim. Acta,40:35-41,1972.

20. Munro, J., and Schachter, M. The presence of two GDP-t-fucose glycoproteinfucosyltransferases in human sera. Arch. Biochem Biophys., 756: 534-542,1973.

21. Parente. J. P., Wieruszeski. J. M., Strecker, G., Montreuil, J., Fournet. B., VanHalbeek. H., Dorland. L.. and Vliegenthart. J. F. G. A novel type of carbohydratestructure present in hen ovomucoid J. Biol Chem., 257:13173-13176,1982.

22. Podolsky. D. K., McPhee. M. S., Alpert, E., Warshaw. A. L, and Isselbacher,K. J. Galactosyltransferase isoenzyme II in the detection of pancreatic cancercomparison with radiologie, endoscopie, and seroiogicai tests. N. Engl. J.Med.. 304:1313-1318,1981.

23. Podolsky, D. K., and Weiser, M. M. Galactosyltransferase activities in humansera: detection of a cancer-associated isoenzyme. Biochem. Biophys. Res.Commun., 65: 545-551,1975.

24. Podolsky, D. K., and Weiser, M. M. Detection, purification and characterisationof a human cancer-associated galactosyltransferase acceptor. Biochem. J.,778:279-287,1979.

25. Podolsky, D. K., Weiser, M. M., Isselbacher, K. J., and Cohen, A. M. A cancerassociated galactosyltransferase isoenzyme. N. Engl. J. Med., 299:703-707,

1978.26. SkJdiqui, B., Whitehead, J. S., and Kim, Y. S. Glycosphmgol.pids in human

colonie adenocarcmoma. J. Biol. Chem., 253: 2168-2175,1978.27. Van Kley. H., Cramer, S., and Bruns, D. E. Serous ovarian neoplastic amylase

(SONA): a potentially useful marker for serous ovarian tumors. Cancer (Phila. ).48:1444-1449,1981.

28. Waren, L., Buck, C. A., and Tuszynski, G. P. Glycopeptide changes andmalignant transformation. A possible role for carbohydrate in malignant behaviour. Biochim. Biophys. Acta, 576:97-127,1978.

29. Weiser, N. M.. Podolsky, D. K., and Isselbacher, K. J. Cancer associatedisoenzyme of serum galactosyltransferase. Proc. Nati. Acad. Sol. u. S. A., 731319-1322,1976.

30. Whitehead, J. S., Feamey, F. J., and Kim. Y. S. Glycosyltransferase andgiycosidase activities in cultured human fetal and colonie adenocarcinoma celllines. Cancer Res., 39:1259-1263,1979.

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