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CA 72-4 Measurement of Tumor-Associated Glycoprotein 72 (TAG-72) As a Serum Marker in the Management of Gastric Carcinoma1

CA 72-4 Measurement of Tumor-Associated Glycoprotein 72 (TAG-72) As a Serum Marker in the Management of Gastric Carcinoma1

( RESEARCH 52, 1222-1227, March 1, 1992] CA 72-4 Measurement of Tumor-associated Glycoprotein 72 (TAG-72) as a Serum Marker in the Management of Gastric Carcinoma1

Fiorella Guadagni, Mario Roseli!, Teresa Amato, Maurizio Cosimeli!, Pasquale Ferri, Vincenzo Casale, Massimo Carlini, Eugenio Santoro, Renato Cavaliere, John W. Greiner, and Jeffrey Schlom2

/ Department of Surgery [M. Co., P. P., R. C.], Department of Digestive Endoscopy /K C.], and II Department of Surgery [M. Ca., E. S.J, Regina Elena Cancer Institute [F. G., T. A.¡,and Department of Surgery, II University of Rome, School of Medicine [M. R.], Rome, Italy, and Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892 [J. W. G., J. S.J

ABSTRACT serum markers specifically associated with a high percentage of patients diagnosed with gastric . Among the serum The presence of three distinct serum markers of carcinoma, tumor- markers currently available for the diagnosis of gastric carci associated glycoprotein 72 (TAG-72; as measured by the CA 72-4 assay), noma are CEA3 and CA 19-9 (8-13). CEA, a M, 180,000 CA 19-9, and carcinoembryonic (CEA), was evaluated in 194 glycoprotein, and CA 19-9, a sialylated Lewis3 antigen, are patients diagnosed with either malignant (n = 94) or benign (n = 100) gastric disease. Of the 94 patients diagnosed with gastric carcinoma, the distinct tumor markers expressed by human gastric percentage of patients whose serum samples were positive for TAG-72, (9, 14). An analysis of the data shows that of all patients CA 19-9, or CEA was 42.6, 31.9, and 20.2%, respectively. Furthermore, diagnosed with gastric carcinoma, 20.6% had positive serum fewer false positive samples were observed for TAG-72 than either CA CEA levels. Of those patients with advanced stage (stage IV) 19-9 or CEA. The analysis of serum TAG-72, CA 19-9, and CEA levels gastric carcinoma, measurable serum CEA was found in 37% in patients diagnosed with early (stage I and II) versus advanced (stage (13). CA 19-9 has also been evaluated as a possible serum III and IV) disease revealed a significantly higher level of TAG-72 and marker for gastric cancer. Elevated serum levels of this tumor CA 19-9 in the serum of patients with advanced stage gastric carcinoma. antigen were found in 26% (15) to 72% (11) of the patients The serum samples were also analyzed to determine whether any advan with gastric carcinoma, while 7% of the patients diagnosed with tage might be gained by simultaneously measuring two or more of the benign gastric disease had positive serum CA 19-9 levels (11). tumor markers. The data clearly indicate that the measurement of TAG- 72 with CA 19-9 significantly increased the percentage of gastric carci The studies revealed some potential utility as well as limitations noma patients with positive serum levels of either antigen. This advantage for monitoring CEA and/or CA 19-9 serum levels in patients was achieved with no significant increase in the number of false positives. diagnosed with gastric carcinoma. The data also suggest the Twenty-one patients were followed postsurgically for up to 3 years to need to evaluate other serum tumor markers for their potential determine whether the appearance or reappearance of TAG-72, CA 19- role in the management of gastric cancer. 9, or CEA accurately predicted disease recurrence. Positive serum TAG- For several years, the potential utility of a novel serum 72 levels correlated with disease recurrence in 7 of 10 patients, compared antigen, TAG-72, has been investigated (16, 17). TAG-72 was with 5 and 2 patients for CA 19-9 and CEA, respectively. The findings originally identified and characterized by MAb B72.3 (18-22) suggest that serum TAG-72 as measured by the CA 72-4 assay may be and the B72.3 epitope has, subsequently, been identified as a a useful marker for late stage gastric carcinoma and its measurement sialosyl-2—»6a-TV-acetylgalactosaminyl epitope (23). A series alone or in combination with CA 19-9 may have utility in the clinical of "second generation" MAbs were produced by immunization management of gastric carcinoma. with purified TAG-72 (24). One such MAb is CC49 which has a higher affinity for TAG-72 than B72.3 and also recognizes INTRODUCTION an epitope on TAG-72 which is distinctive from that recognized by B72.3. CC49 was used in combination with B72.3 to develop Although the incidence and death rate from gastric cancer in a double-determinant immunoradiometric assay, designated the United States have declined in past decades, it remains a CA 72-4 (25, 26), which detects TAG-72 in sera or body fluids common cause of cancer-related death (1, 2). The highest of carcinoma patients. Using the CA 72-4 assay, several groups incidence rates of gastric carcinoma are found in certain Med have studied the presence of TAG-72 in the serum of patients iterranean countries, in Eastern Europe, and in the Pacific Rim, diagnosed with gastrointestinal malignancies (27-30). The with Japan having the highest incidence worldwide (3-5). In studies revealed that a significant percentage of patients diag Italy, the incidence of gastric carcinoma is 25.1/100,000 for nosed with gastrointestinal carcinoma whose serum CEA levels males and 16.1/100,000 for females, representing the second were negative had elevated TAG-72 (>6 units/ml), indicating a leading cause of cancer-related death in males and the third most common cause of cancer-related deaths (14,500/year, in complementarity between the two tumor . Moreover, the measurement of serum TAG-72 in patients during postsur- the past 5 years) (3). gical follow-up was predictive of the appearance of recurrent The early stage of gastric carcinoma is often complicated and disease (30). extremely difficult to diagnose due to presentation with vague, The present study evaluates the preoperative serum levels of nonspecific symptoms which are sometimes associated with TAG-72, CEA, and CA 19-9, alone or in combination, in nonmalignant diseases (6, 7). The development of additional patients diagnosed with primary gastric carcinoma or benign methods for this diagnosis includes the desire for efficient, gastric disease. The findings suggest the potential utility of noninvasive diagnostic procedures such as the identification of using the CA 72-4 assay to detect serum TAG-72, either alone Received 10/14/91; accepted 12/17/91. or in combination with CA 19-9, for the diagnosis of gastric The costs of publication of this article were defrayed in part by the payment carcinoma. In addition, a longitudinal follow-up of gastric of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. carcinoma patients also revealed the potential utility of the CA ' This work has been partially supported by a grant from A.I.R.C., 1991. 72-4 assay alone, or in combination with CA 19-9, as part of 2To whom requests for reprints should be addressed, at Laboratory of Tumor Immunology and Biology, Building 10, Room 8B07, National Cancer Institute, 3The abbreviations used are: CEA, ; TAG-72, tumor- NIH, Bethesda, MD 20892. associated glycoprotein 72; MAb, monoclonal . 1222

Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 1992 American Association for Cancer Research. ÇA72-4 MEASUREMENT OF TAG-72 AS SERUM MARKER the clinical management of postsurgical gastric carcinoma Table 2 Correlation of presurgical TAG-72, Ca 19-9 and CEA serum levels and clinical stage in gastric cancer patients patients. levelsStageI Serum antigen of 19-9>37 MATERIALS AND METHODS patients14 >6units/ml1 units/ml4 >5ng/ml1 (7.1)° Patient Information. One hundred ninety-four patients, 94 with his (28.6) (7.1) II 16 2(12.5) 2(12.5) 2(12.5) tologically diagnosed primary gastric [SO males, 44 III 36 19(52.8) 11 (30.6) 7 (19.5) females; mean age, 58 ±1.3 (SE) years, ranging from 30 to 89 years IVTotalNo. 2894TAG-72 18(64.3) 13(46.4) 9 (32.2) old], and 100 patients with histologically confirmed benign [gastritis, 40 (42.6)CA 30(31.9)CEA 19 (20.2) ulcer, adenomas, polyps] gastric disease [54 males, 46 females; mean " Numbers in parentheses, percentage of patients within each stage of malig age, 53 ±1.9 years] were evaluated. All patients with malignant disease nant gastric cancer in which their serum samples contain positive titers of the underwent surgery for their primary tumor at the Department of indicated . Surgery, while patients diagnosed with benign gastric disease underwent endoscopie examination at the Department of Digestive Endoscopy of assay-monoclonal antibody assay. As shown in Table 1, 42.6% the Regina Elena National Cancer Institute, Rome, Italy. Malignant of the sera from patients diagnosed with primary gastric carci gastric disease was pathologically staged according to the tumor-nodes- noma had elevated TAG-72 levels (>6.0 units/ml). In contrast, metastasis classification (Union International Contre le Cancer tumor- nodes-metastasis classification of malignant tumors, 1983): Stage I (n only 1 of 100 of the sera from patients with benign gastric = 14); Stage II (n = 16); Stage III (n = 36); and Stage IV (n = 28). disease had positive TAG-72 levels. CA 19-9 serum levels were Serum samples were drawn within 1 week prior to surgery; 3, 7, and elevated (>37.0 units/ml) in 31.9 and 7% in patients with 14 days postoperatively; and every 3 months during clinical follow-up. malignant and benign disease, respectively. Serum CEA was Serum samples from patients with benign disease were drawn at the elevated (>5.0 ng/ml) in 20.2% of sera from patients with time of endoscopy. All samples were aliquoted, coded, and stored at gastric carcinoma and 9% of sera from patients with benign -20°Cuntil assays were performed. disease. CA 72-4, CEA, and CA 19-9 Radioimmunoassays. Serum TAG-72 The relationships between serum TAG-72, CA 19-9, and antigen levels were determined by a double-determinant immunoradi- CEA levels and the clinical staging of the patients with gastric ometric assay , CA 72-4, supplied by Centocor (Malvern, PA), as carcinoma were also evaluated (Table 2). In particular, positive described previously (25). Samples and TAG-72 standards were assayed serum TAG-72 levels were found in patients diagnosed with in duplicate. Briefly, 100 n\ of specimen in the presence of 100 n\ of phosphate buffer were incubated at 37°Cfor4 h with beads coated with advanced stage gastric carcinoma. Of the 40 patients which had positive serum TAG-72 levels, 37 were diagnosed with either MAb CC49. The beads were washed 3 times with distilled water and incubated with '"I-B72.3 for 18 to 20 h at 4'C. After 3 washes with stage III or stage IV gastric carcinoma. Likewise, elevated distilled water, bound radioactivity was measured in a gamma counter. serum CA 19-9 and CEA were also found predominantly in TAG-72 levels, expressed as units/ml, were determined by converting sera samples from patients with advanced stage gastric carci cpm to concentration values using a concurrently obtained standard noma (Table 2). Fig. 1 summarizes the statistical analysis of curve. The cutoff limit for this assay was set at 6 units/ml as suggested the mean CA 72-4, CEA, and CA 19-9 presurgery serum levels (25). CEA serum levels were determined using a CEA RIA MAb kit for gastric carcinoma patients classified as early (stages I and (Abbott Laboratories, Inc., Chicago, IL). Several different cutoff limits, II) and advanced (stages HI and IV) disease. The mean serum ranging from 2.5 to 10.0 ng/ml, have been used for the analysis of CEA TAG-72 levels from patients with stage I and II gastric carci serum levels (31-33). In the present study, we used a cutoff limit of 5.0 ng/ml for better specificity. CA 19-9 serum levels were determined as noma was 3.3 ±0.6, while the mean value from patients with stage III and IV disease was 24.1 ±7.8 (Fig. 14) (P < 0.002). previously described using the suggested cutoff limit of 37 units/ml (12). Measurement of serum TAG-72, CEA, and CA 19-9 was done A statistically significant difference between serum CA 19-9 without any prior knowledge of the clinical diagnosis. A significant levels in patients diagnosed with early and advanced gastric increase of the serum marker levels was considered, either when nega carcinoma was also observed. As shown, the mean serum CA tive serum levels became positive or when there was an increase of 19-9 level from patients with stage III or IV gastric carcinoma >50% over the mean of previous positive levels. was 92.3 ±25.2 compared with 23.2 ±4.0 from patients Statistical Analysis. A Student t test (STATVIEW softwear package) diagnosed with stage I or II disease (P < 0.05) (Fig. \B). No was used to evaluate statistical differences among the serum tumor statistical difference was observed for differences in serum CEA markers. levels between those patients diagnosed with early and advanced disease. Thus, these results indicate that measurement of TAG- RESULTS 72 may be useful in differentiating early versus advanced gastric carcinoma. Sera from 94 patients with primary gastric carcinoma and Studies were then conducted to determine if there was any 100 patients with benign gastric disease were evaluated for the advantage in the use of combinations of the CA 72-4, CA 19- presence of TAG-72 using the CA 72-4 assay, for 19-9 using 9, and CEA assays. Fig. 2 illustrates the presence of TAG-72 the CA 19-9 assay, and for CEA using the CEA-radioimmuno- and/or CA 19-9 in the sera of the 94 patients diagnosed with

Table 1 Summary of TAG-72, CA 19-9, and CEA levels in sera of patients diagnosed with malignant or benign gastric diseases Serum tumor antigen levels (units/ml)DiagnosisCarcinoma TAG-72 9-9(units/ml)Mean68.9 (ng/ml)Mean10.4 of of patients of patients of patients patients94 >6units/ml40 >37units/ml30(31.9) >5ng/ml19 ±4.2" (42.6)' ±16.7 ±1.9 (20.2) BenignNo. 100Range1-478.01-6.1Mean17.71.9 ±0.2No. KDRange1.5-10401.5-122.9CAI 15.1 ±3.2No. 7(7)Range1-184.21-23.7CEA 3.4 ±0.3No. 9(9) " Mean ±SE. '' Numbers in parentheses, percentage of patients' serum samples with detectable levels of the respective tumor antigen. 1223

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(56.4%) serum samples were positive for either tumor marker. 40 Similar analyses were done with TAG-72 versus CEA (Fig. 3) and CEA versus CA 19-9 (Fig. 4). As shown in Fig. 3, of 94 patients serum samples 8 (8.5%) were CEA positive, and 11 (11.7%) were positive for both CEA and TAG-72. Of the - 301 0)

1000 n =23O 17o00 = 20 I in 100- S 10 0o° °o < 6 s '•osO o00 CE 00° 111 ' p <0.002 I 3.3t0.6 | 24.1±7.8 (O 00 o 0 0 0o° 0 I + II III + IV „¿0» ¡ 0°o0o°o°o0°o0°00 a S 00•••"n °00°°o ° 0° » B °o ° ° o n=41 o °n = 13 120 10 100 1000 3 100 CA19-9 SERUM LEVELS (U/ml) Fig. 2. Serum TAG-72 and CA 19-9 levels in patients diagnosed with gastric carcinoma. , serum cutoff values for TAG-72 (6 units/ml) and CA 19-9 (37 80 units/ml), n, number of patients in each quadrant (i.e., 23 patients were TAG 72 LU positive and CA 19-9 negative).

3 60- K LU lUUU:100:10-6 V) 290ooo0 11oo0 o> 37

20-

p<0.05 92.3±25.2

°00 0 III + IV 0o00 0 «i O» o0°0° 0° °0°O °o00ooo ° o

'n= O0O o O n o®300°000 0 0 O 40 ^?oo 0Q oo°oo ° n= 46n=n=8o o E 10 100 1000 Ì 30- CEA SERUM LEVELS (ng ml) M pj Fig. 3. Serum TAG-72 and CEA levels in patients diagnosed with gastric 111 carcinoma. See Fig. 2 for explanation of symbols. tu 20-

1UUU-100-37io-n CE LU = 2000 n=lOO0 ° OT 10-

111 E °o0 ° o 5 - D

00 p

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Table 3 Summary of CA 72-4, TAG-72, and CEA serum levels in patients with Serum TAG-72, CA 19-9, and CEA levels were followed benign or malignant disease longitudinally in 21 patients for up to 3 years postsurgery for MalignantTAG-72 primary gastric carcinoma or until the clinical diagnosis of of of patients"40 patients"42.6patients'1 patients*1 recurrence of malignant disease (Table 4). Eleven of the 21 patients with no clinical evidence of disease had no detectable serum levels of any of the 3 tumor antigens. One patient (PF) CEA 19 20.2 7 7 CA 19-9 30 31.9 9 9 without clinical evidence of disease had a positive serum CEA TAG-72 and/or CEA 48 51.1 8 8 at 207 days postsurgery. Ten clinical recurrences were diag TAG-72and/or CA 19-9 53 56.4 9 9 nosed in 9 patients (patient RA, 2 recurrences). Serum TAG- TAG-72 and/or CEA 39 41.5 12 12 All 3 markersNo. 57%of 60.6BenignNo.13%of 13 72 levels were elevated in 7 of the 10 clinical recurrences, " Number and percentageof carcinoma patients with elevatedtumor antigen whereas serum CA 19-9 and CEA levels were positive in 5 and serum levels(total patients evaluated,94). bNumberand percentageofbenignpatientswith elevatedtumor antigenserum 2 cases, respectively. In all cases, detectable serum levels of TAG-72 either occurred prior to or concomitant with the levels(total patients evaluated,100). clinical diagnosis of recurrent disease. As an example, Fig. 5 illustrates the changes in serum TAG-72 (panel A), CA 19-9 remaining 75 patients whose serum samples were CEA nega tive, 38.7% were TAG-72 positive. When combining the meas (panel B), and CEA (panel C) in patient DSA who was diag urement of serum CEA with TAG-72, serum samples from 48 nosed with stage II gastric carcinoma and was followed for approximately 2 years after surgical resection of the primary of the 94 (51.1%) patients were positive. The relationship between serum CEA and CA 19-9 in the serum samples from tumor. Prior to surgery, serum samples from patient DSA were positive for CEA and negative for TAG-72 and CA 19-9. During these patients was also investigated (Fig. 4). Serum from 9 of the postsurgical follow-up, positive TAG-72 serum was de the 94 patients was positive for CEA, and serum samples from tected, whereas serum CA 19-9 and CEA remained negative. 10 patients contained positive levels of both CEA and CA 19- Elevation of serum TAG-72 was detected at 297 days prior to 9. Of the 75 patients whose serum CEA levels were negative, 26.7% had positive CA 19-9 serum levels. Combining the clinical recurrence. measurement of both tumor markers revealed that 41.5% of serum samples were positive for either CEA or CA 19-9. DISCUSSION Table 3 summarizes the percentage of patients diagnosed with gastric carcinoma (n = 94) or with benign gastric disease The present study indicates that the measurement of serum (n = 100) whose serum samples contained either TAG-72, CA TAG-72 levels may be an important component in the diagnosis 19-9, and/or CEA. Serum TAG-72 (42.6%) alone was found and clinical follow-up of patients with malignant gastric disease. in a higher percentage of patients with gastric carcinoma than When compared with other serum tumor markers that are either CEA (20.2%) or CA 19-9 (31.9%) alone. Furthermore, currently used for the diagnosis and monitoring of patients for combining serum TAG-72 measurement with either CA 19-9 gastric carcinoma, i.e., CA 19-9 and CEA, a higher percentage or CEA increased the percentage of serum positive to 56.4 and of patients with gastric cancer had positive TAG-72 serum 51.1%, respectively. It should be noted that a concomitant levels. In addition, the specificity of serum TAG-72 for differ increase in the percentage of false-positive serum levels was not entiating carcinoma versus benign gastric disease was better observed when TAG-72 measurement was combined with either than for either CA 19-9 or CEA. The 94 patients diagnosed CA 19-9 or CEA. Sixty % of gastric cancer sera were positive with gastric carcinoma were also staged according to tumor- when using all three markers. nodes-metastasis classification and the presence of serum TAG-

Table 4 Summaryof longitudinalevaluationof TAG-72serumlevelsin gastricpatients detectableelevationof tumor antigens"TAG-72ND*ND211NDNDNDND207368ND63ND16NDNDNDNDND6354NDNDCEANDNDNDNDND207NDNDNDND102ND16NDNDNDNDNDNDNDNDNDCA of clinical PatientFGBLDSAMDPAPFPURASFFEGFIFLMLPMPVUADADAPCMFAPAPresurgeryStage19-9I TAG-72 CEA CA (days)860427665f372505241384550C989160C43460C769155504757145130180f200C80°First19-9NDNDNDNDNDNDNDND368ND63ND16NDNDNDNDND637NDNDTimeevidence(days)NEDNED508NEDNEDNEDNED248440NED133NED45NEDNEDNED365NED639717340 -IIII +II - +IIII +IIIIIIIII - -

-IIIIII - +

+III + + -III + + +IIIIIIIII

+IV + - +IV + +IV + +IVFollow-up-

" Days postsurgery. * ND, not detectable; NED, no evidence of disease. cPatientsin which detectableserum TAG-72, CEA, and/or CA 19-9precededthe time of diagnosisof clinicalrecurrentdisease. 1225

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rately. Recent findings have suggested a complementarity among various serum tumor markers which may be exploited in the diagnosis of gastrointestinal carcinoma (30). Ideally, one would envision that the complementarity might increase the sensitivity with respect to clinical diagnosis with little change in the specificity (i.e., little increase in false positives). For example, the present data indicate that combining the measure ment of serum TAG-72 with CA 19-9 increased the percentage of patients diagnosed with gastric carcinoma who also had measurable serum titers of either tumor antigen. At the same

10 100 time, there was no change in the number of false positive serum DAYS POST SURGERY samples (i.e., patients with benign gastric disease), suggesting that the simultaneous measurement of TAG-72 and CA 19-9 may selectively identify a higher percentage of patients with 100 gastric cancer. Additional studies with higher numbers of sam ples are needed to further investigate whether the analysis of I » multiple serum tumor markers may be advantageous in the (A diagnosis of gastric carcinoma.

LU One of the important applications of any serum marker is -1i 10 the ability to use the measurement of the serum tumor antigen in predicting the clinical course of the malignant disease, par ticularly, the diagnosis of disease recurrence. In the present study, 21 patients diagnosed with primary gastric cancer were followed postsurgery for up to 3 years or to time of disease 10 100 recurrence. As seen in Table 4, none of the 12 patients with no DAYS POST SURGERY clinical evidence of disease had positive TAG-72 levels. Six of 9 patients [1 patient (RA) had 2 recurrences], however, with clinically confirmed disease recurrence had elevated serum TAG-72 levels. In 5 of the 6 patients with recurrent disease, positive serum TAG-72 levels were detected prior to the clinical diagnosis (Table 4) and, in some patients, positive serum TAG- 72 levels preceded clinical evidence of disease by 100 to 300 days. Monitoring both serum CA 19-9 as well as CEA did not correlate as well as TAG-72 with the onset of recurrent disease. While additional studies with larger population groups and different population bases are needed, these findings indicate that the measurement of serum TAG-72 levels may be useful in the clinical diagnosis of primary and recurrent gastric cancer. 10 100 DAYS POST SURGERY REFERENCES Fig. 5. Longitudinal postsurgery evaluation of serum TAG-72 (A), CA 19-9 (A), and CEA (C) in patients diagnosed with stage II gastric adenocarcinoma. 1. Silverberg, E. Cancer statistics. CA Cancer J. Clin., 36:9-25, 1986. Arrow, time of surgery; , serum cutoff values for each of the tumor antigens. 2. Devesa, S. S., and Silverman, D. T. Cancer incidence and mortality trends in the United States 1935-1974. J. Nati. Cancer Inst., 60: 545-561, 1978. 3. Decarli, A., and LaVecchia, C. Cancer mortality in Italy, 1985-1987. Tumori, 77:1-6, 1991. 72, CA 19-9, and CEA in the different stages were evaluated. 4. Dunham, L. J., and Bailar, J. ( '., III. World maps of cancer mortality rates Serum levels for both TAG-72 and CA 19-9 were highly cor and frequency ratios. J. Nati. Cancer Inst., 41: 155-203, 1968. related with the advanced stages of gastric carcinoma. These 5. WHO. World Health Statistics Annals, 1988. observations suggest that the presence in the serum of TAG-72 6. Goldsmith, H. S., and Ghosh, B. C. Carcinoma of the stomach. Am. J. Surg., 720:317-319, 1970. and CA 19-9 closely reflects the clinical staging of the disease 7. Adashek, K., Sanger, J., and Longmire, W. P., Jr. Cancer of the stomach. and that additional studies are needed which may elucidate the Review of consecutive ten-year intervals. Ann. Surg., 189: 6-10, 1979. roles that those tumor markers play in the biology of human 8. Goldenberg, D. M., Neville, A. M., Carter, A. C., Go, V. L., Holyoke, E., Kjisselbacher, K., Schein, P., and Schwartz, M. Carcinoembryonic antigen: gastric carcinoma. its role as a marker in the management of cancer: a National Institutes of It is generally agreed that the sensitivity as well as the Health Consensus Development Conference. Ann. Intern. Med., 94: 407- 409, 1981. specificity of a single serum tumor marker for the diagnosis of 9. Sikorska, H., Shuster, J., and Gold, P. Clinical applications of carcinoem- primary and recurrent carcinoma is limited. No one serum bryonic antigen. Cancer Detect. Prev., 12: 321-355, 1988. 10. Herlyn, M., Sears, H. F., Steplewski, /... and Koprowski, H. Monoclonal tumor marker will unfailingly predict the presence of malignant antibody detection of a circulating tumor-associated antigen. I. Presence of disease or differentiate between benign versus malignant dis antigen in sera of patients with colorectal, gastric, and pancreatic carcinoma. ease. The present data clearly indicate that serum TAG-72, CA J. Clin. Immunol., 2: 135-140, 1982. 11. Ritts, R. E., Jr., Del Villano, B. C., Go, V. L., Herberman, R. B., Klug, T. 19-9, and CEA appear in 42.6, 31.9, and 20.2%, respectively, L., and Zurawski, V. R., Jr. Initial clinical evaluation of an immunoradiome- of the serum of patients diagnosed with gastric carcinoma tric assay for CA 19-9 using the NCI serum bank. Int. J. Cancer, 33: 339- (Table 1). Therefore, a majority of patients (i.e., >50%) with 345, 1984. 12. Del Villano, B. C., Brennan, S., Brock, P., Bucher, C., Liu, V., McClure, M., malignant gastric disease do not contain measurable serum Rake, B., Space, S., Westrick, B., Schoemaker, H., and Zurawski, V. R., Jr. levels of any of these three tumor markers if analyzed sepa Radioimmunometric assay for a monoclonal, antibody-defined tumor 1226

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marker, CA 19-9. Clin. Chem., 29: 549-552, 1983. A., Greiner, J. W., Simpson, J. F., Molinolo, A., Noguchi, P., and Schlom, 13. Koga, T., Kano, T., Souda, K., Oka, N., and Inokuchi, K. The clinical J. Generation and characterization of B72.3 second generation monoclonal usefulness of preoperative CEA determination in gastric cancer. Jpn. J. Surg., reactive with the tumor associated glycoprotein 72 antigen. Cancer 17: 342-347, 1987. Res., 48: 4588-4596, 1988. 14. Sipponen, P., and Lindgren J. Sialylated Lewis' determinant CA 19-9 in 25. Gero, E. J., Colcher, D., Ferroni, P., Melsheimer, R., Giani, S., Schlom, J., benign and malignant gastric tissue. Acta Pathol. Microbiol. Immunol. and Kaplan, P. The CA 72-4 radioimmunoassay for the detection of the Scand. Sect. A, 94: 305-311, 1986. TAG-72 carcinoma associated antigen in serum of patients. J. Clin. Lab. 15. Staab, H. J., Hournung, A., Anderer, F. A., and Kieninger, G. 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Fiorella Guadagni, Mario Roselli, Teresa Amato, et al.

Cancer Res 1992;52:1222-1227.

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