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Purpose: To clarify the differences in prognosis of colorectal cancer patients based on the expression of sialyl Lewisaa sialyl Lewisx and sialyl Tn antigens in serum and tumor tissue., Patients and Methods: Preoperative serum levels (by radioimmunoassay) and tumor tissue expression (by immunohistochemistry) of these antigens were simultaneously determined in 52 patients. For each antigen, patients were classified into one of four groups: Group S-/T-, S-/T+, S+/T- and S+/T+. (S denotes serum, T denotes tumor tissue, and negative and positive represent expression)., Results: For sialyl Lewisa antigen, the survival time of Group S+/T+ was significantly shorter than Group S-/T- or Group S-/T+ (p=0.027 or p=0.032, respectively). For sialyl Lewisx antigen, the survival time of Group S-/T+ was significantly shorter than Group S-/T- (p=0.048)., Conclusion: Increased expressions of sialyl Lewisa antigen in serum and sialyl Lewisx antigen in tumor tissue may be associated with poor prognosis in colorectal cancer patients. more...

This study aimed to determine whether sialyl Lewis(a) (Le(a)), sialyl Lewis(x )(Le(x)), or sialyl Tn antigen expression could identify a subset of node-negative colorectal cancer patients that are at high risk for recurrence after curative surgery. Tumor tissue samples from 90 patients with node-negative colorectal cancer, who had undergone surgical resection, were analyzed immunohistochemically for the expression of each antigen. Patients were classified as having low or high antigen expression depending on whether more or less than 40% of the field showed positive staining. The main outcome measure for each variable was disease-free interval. Sialyl Le(a), sialyl Le(x), and sialyl Tn antigens were expressed in 53 (58.9%), 41 (45.6%), and 34 (37.8%) carcinomas, respectively. The median follow-up was 83.5 months. Patients with high sialyl Le(x) expression had shorter disease-free intervals than those with low sialyl Le(x) expression (P = 0.0041); the expression of sialyl Le(a) or sialyl Tn antigens did not show a significant relationship with disease-free survival. Cox's regression analysis revealed that sialyl Le(x) expression was an independent predictor for disease-free survival, separate from T factor or tumor location. High sialyl Le(x) expression may be useful in identifying a subset of node-negative colorectal cancer patients who are at high risk for recurrence. more...

We examined the immunohistochemical expression of sialosyl-Tn antigen in the colorectal cancer tissues of 116 patients who underwent curative resection to determine the association between patient prognosis and the expression of sialosyl-Tn in two different tissues: carcinoma and transitional mucosa. Negative or positive expression of sialosyl-Tn in the carcinoma and transitional mucosal tissues were denoted as CA- or CA+ and TM- or TM+, respectively. Patients were classified into one of four groups: CA-/TM-, CA-/TM+, CA+/TM-, and CA+/TM+. CA-/TM- was observed in 13 patients and CA-/TM+, CA+/TM-, or CA+/TM+ was observed in 103 patients. The difference in five-year survival between the CA-/TM- group and all the other groups was statistically significant (P = 0.0457), and multivariate analysis showed that sialosyl-Tn expression in at least one of the two tissues was an independent prognostic factor. We conclude that the evaluation of sialosyl-Tn expression in carcinoma as well as transitional mucosa is useful for predicting survival in colorectal cancer patients. more...

Preoperative serum levels of sialyl Lewis(a) (CA19-9), sialyl Lewis(x) (SLX) and sialyl Tn (STN) antigens in 180 patients with gastric cancer were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). The patients were divided into low and high antigen groups. Multivariate logistic regression analysis revealed the following independent predictive factors for high antigen levels [odds ratio]: liver metastasis for CA19-9 [4.40], SLX [9.90], STN [39.65] and CEA [5.14]; peritoneal dissemination for SLX [4.78] or STN [13.01]; venous invasion for CEA [3.56]; lymph node metastasis for CA19-9 [4.51]. In addition, high CA19-9 levels were independently related to lymph node metastasis in patients with stage I or II tumors. In conclusion, high serum levels of CA19-9, SLX and STN are associated with liver metastasis, while high serum levels of SLX and STN are associated with peritoneal dissemination. In addition, high serum CA19-9 levels may represent an independent predictor for lymph node metastasis. more...

Aims: To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients., Methods: Pre-operative serum levels of STN, sialyl Lewis(a)antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis., Results: Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P<0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patients. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis., Conclusions: Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer. more...

The serum levels of sialyl Lewis(a) (CA19-9), sialyl Lewis(x) (SLX), sialyl Tn (STN) and carcinoembryonic antigen (CEA) in peripheral venous blood and tumor drainage venous blood of colorectal cancer patients were examined to determine their value as prognostic factors after surgery. Blood samples were obtained from the peripheral vein and from the tumor drainage vein from 124 colorectal cancer patients during surgical excision of the tumor. The patients were divided into high-antigen and low-antigen groups for each antigen in each location. Serum levels of SLX, STN and CEA in tumor drainage venous blood (d-SLX, d-STN and d-CEA, respectively) were significantly higher than in peripheral venous blood (p-SLX, p-STN and p-CEA, respectively). The survival time after surgery for patients with high d-SLX or d-CEA levels and low levels of the same antigen in peripheral venous blood was significantly shorter than the survival time for those patients with low levels of antigen at both sites (p = 0.0003 or p = 0.0406, respectively). Cox's regression analysis revealed that a high d-SLX or high d-CEA level was an independent prognostic variable for patient survival. In conclusion, determining d-SLX or d-CEA is more useful than p-SLX or p-CEA in predicting the outcome for colorectal cancer patients., (Copyright 2001 S. Karger AG, Basel) more...

Preoperative serum levels of sialyl Lewis(a) (CA 19-9), sialyl Lewis(x) (SLX), and sialyl Tn (STN) antigens in colorectal cancer patients were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). A total of 308 patients who underwent resection for a colorectal cancer were divided into low and high antigen groups (higher or lower than a selected diagnostic-based cutoff value). The cutoff values were 37 U/ml for CA19-9, 38 U/ml for SLX, 45 U/ml for STN, and 2.5 ng/ml for CEA. The American Joint Committee on Cancer Classification and Stage grouping was used to classify the tumors. Statistical tests were conducted using univariate and multivariate logistic regression analyses. For CA19-9, 81 patients (26.3%) were assigned to the high antigen group: for SLX, 39 (12.7%); for STN, 33 (10.7%); and for CEA, 133 (43.2%). Multivariate logistic regression analysis revealed that predictive factors associated with high antigen levels were female sex (odds ratio [OR], 1.78 vs male sex), T4 (OR, 3.26 vs T1/T2), and M1 (OR, 3.35 vs M0) for CA19-9; M1 (OR, 6.40 vs M0) for SLX; mucinous carcinoma (OR, 8.45 vs well differentiated adenocarcinoma) and M1 (OR, 8.24 vs M0) for STN; and mucinous carcinoma (OR, 7.21 vs well differentiated adenocarcinoma), T3/T4 (OR, 3.84/4.18, respectively, vs T1/T2), and M1 (OR, 6.39 vs M0) for CEA. In conclusion, high serum levels of CA19-9, SLX, and STN are strongly associated with distant metastasis. In addition, high serum levels of CA19-9 may be an independent predictor for female gender and T4, and high serum levels of STN may be an independent predictor for mucinous carcinoma. more...

In this study, we examined the preoperative serum levels of sialyl Lewisa, sialyl LewisX, sialyl Tn, and carcinoembryonic antigen in 243 colorectal cancer patients in order to clarify the role of these antigens as prognostic factors after curative surgery. The patients were divided into two groups: low and high antigen groups (lower and higher than a selected diagnostic-based cut-off value). Patients with high serum levels of sialyl Lewisa and carcinoembryonic antigen had shorter disease-free intervals than those with low serum levels of the respective antigen, although sialyl Lewisx and sialyl Tn showed no significant differences. Multivariate analysis revealed that three independent prognostic variables, including depth of tumor invasion, lymph node metastasis, and serum sialyl Lewisa level, did prove to have value in predicting disease-free interval. In conclusion, among the four antigens examined in this study, the preoperative serum level of sialyl Lewisa is the only independent prognostic variable for recurrence after curative resection of colorectal cancer. more...

To examine the prognostic value of assessing the concentration of circulating sialyl Tn antigen (STN) after surgery, we determined serum STN levels in peripheral venous blood (designated "p-") in 308 colorectal cancer patients and what we have termed the "d-p gradient" (obtained by subtracting the serum concentration in peripheral venous blood from that in the tumor's drainage venous blood) in 144 patients. The prognostic value of STN and carcinoembryonic antigen (CEA) was compared. Patients were divided into low or high p-antigen groups and low, intermediate, or high d-p gradient groups. Univariate and multivariate analyses revealed that high STN d-p gradient, high p-CEA, or high CEA d-p gradient were each independent variables for poor patient outcome after surgery, separate from stage. In conclusion, a high STN d-p gradient was a predictor of poor outcome after resection for colorectal cancer, while p-STN was not independent of stage. more...

Recent studies delineated two different patterns of tumor growth in colorectal carcinoma characterized as polypoid and nonpolypoid (PG-type and NPG-type, respectively). We quantified serum sialyl Lewis (Le)a (CA19-9), sialyl Lex (SLX), sialyl Tn (STN), and carcinoembryonic antigen (CEA) in 269 colorectal cancer patients to establish whether their levels correlated with any biological or clinical differences between PG-type and NPG-type cancer. Patients were divided into high and low antigen groups (higher or lower than a selected diagnostic-based cut-off value) and compared. Statistical testing was by univariate and multivariate (logistic regression) analyses. Forty-seven (17.5%) patients with PG-type and 222 (82.5%) with NPG-type cancer were studied. In contrast to NPG-type, the characteristics of the PG-type cancers included a low rate of lymph node metastasis and a high serum STN level. In contrast to a low STN level, a high STN level was independently related to the presence of distant metastasis in patients with PG-type cancer, and also to the presence of distant metastasis and large-sized tumor in patients with NPG-type cancer. These data suggest that differences in STN levels in the serum of patients with PG-type or NPG-type colorectal carcinomas may be at least partly responsible for different tumor progression behavior. more...

Colorectal tumors can be classified based on their growth pattern into the polypoid growth type (PG-type) and nonpolypoid growth type (NPG-type). We examined sialyl Tn antigen expression in advanced colorectal carcinomas that were classified as PG-type and NPG-type cancers in order to ascertain whether or not such expression correlates with other biologically and clinically important differences. A total of 94 advanced colorectal carcinomas were examined for sialyl Tn antigen expression, which was immunohistochemically detected by the monoclonal antibody TKH2. Univariate and multivariate analyses using logistic regression models were performed. Forty carcinomas (42.6%) were negative and 54 (57.5%) were positive for sialyl Tn antigen. Eighteen carcinomas (19.2%) were of PG type and 76 (80.8%) of NPG type. NPG-type cancers had a higher proportion of positive lymph node metastasis than PG-type cancers. Furthermore, sialyl Tn antigen was less often detected in NPG-type cancers (39 of 76; 51.3%) than in PG-type cancers (15 of 18; 83.3%; p = 0.0167). Multivariate analysis showed that two variables, lymph node metastasis and sialyl Tn antigen expression in carcinoma, were independently related to tumor growth patterns, that is NPG type and PG type. These data suggest that the difference in sialyl Tn antigen expression between two kinds of tumor growth patterns of advanced colorectal carcinomas, PG type and NPG type, may reflect different biological behaviors during tumor progression., (Copyright 2000 S. Karger AG, Basel.) more...

Background: To investigate colorectal cancer-related carbohydrate antigen release and distribution, we evaluated serum levels of sialyl Le(a) (CA19-9) and sialyl Le(x) antigen (SLX) in blood samples obtained from both a peripheral vein and a tumor's draining vein., Methods: Blood samples were obtained during surgery from 126 patients. Based on these samples, patients were placed into a high-antigen group, with a concentration above a selected cutoff value, or into a low-antigen group, with a tumor marker concentration below that same value. The blood samples obtained from peripheral veins were designated by the "p" prefix, and samples from drainage veins were designated by the "d.", Results: Serum d-SLX levels were significantly higher than p-SLX levels (P < .0001), although there was no difference between those of d-CA19-9 and p-CA19-9. Only 1 (3.6%) of 28 patients in the high d-CA19-9 group had a low p-CA19-9. In contrast, 6 (33.3%) of 18 patients in the high d-SLX group had low p-SLX levels (P = .0103). Correlations between pathological variables and either p-CA19-9 levels or d-CA19-9 levels were similar. However, both distant metastasis and venous invasion did prove to be independent variables related to d-SLX levels, as shown by logistic regression analysis., Conclusions: SLX may drain predominantly via the draining veins of colorectal tumors into portal circulation, whereas CA19-9 may drain via another route. more...

Sialyl-Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. In the present study, we compared the serum level of STn antigen in 14 patients with benign diseases of the biliary tract and pancreas, 15 patients with bile duct cancers, and 9 patients with cancer of the pancreas. High levels of serum STn (>45 U/ml) were frequently detected in patients with carcinoma of the biliary tract (53.3%) or pancreas (55.6%), compared with the detection of high levels in those with benign diseases (14.3%; P < 0.05). Serum levels of STn did not correlate with the presence of jaundice, cholangitis, or pancreatitis, or with the level of carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9. In cancer tissues, the expression of STn antigen detected by immunostaining correlated significantly with serum STn (P < 0.05). Our results indicate that measurement of serum STn level may be potentially useful for the diagnosis of carcinomas of the biliary tract and pancreas, particularly when combined with other tumor markers such as CEA or CA19-9. more...

Purpose: Sialyl Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. We compared the proportion of specimens of flat-type colorectal cancers expressing STn with that of polypoid cancers, by examining the immunohistochemical reactivity of STn in various morphologic types of early and advanced colorectal cancers., Methods: A total of 111 biopsies from the colorectal area were examined for STn expression, including 11 adenomas, 58 early cancers, and 42 advanced cancers. Each section was stained immunohistochemically for STn antigen. In each section, we examined STn expression in the cancer area, adjacent mucosa, and normal epithelium., Results: STn expression was detected in 90.9 percent of adenomas, 36.2 percent of early cancers (T1), 64.3 percent of advanced cancers (>T1), and 52 percent of mucosa adjacent to cancer. The morphology of cancer tissue did not influence the number of specimens exhibiting STn antigen expression in mucosa adjacent to cancer cells. STn antigen was rarely expressed in flat or depressed-type early cancers (T1; 7.1 percent), and the expression was higher in moderately than in well-differentiated adenocarcinomas. In advanced cancers (>T1), a similar proportion of protruding and small ulcerative cancers expressed STn., Conclusion: Our results suggest that the low expression of STn antigen in flat-type cancers may be the result of different mechanisms of cellular transformation during carcinogenesis from the usual adenoma-carcinoma sequence in colorectal neoplasms. more...

The immunohistochemical expression of sialylated and non-sialylated forms of both Le(x) and Le(a) were studied in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in 32 metastatic lymph nodes and 9 hepatic lesions, using an indirect immunoperoxidase staining. Their antigens were expressed in normal mucosa with the following frequencies: Le(a), 95.2% (40/42); sialyl Le(a), 88.1% (37/42); Le(x), 95.2% (40/42); and sialyl Le(x), 17.0% (7/42), whereas in carcinomas, the respective rate of frequency were: 78.2% (68/87); 78.2% (68/87); 90.8% (79/87); and 93.1% (81/87). Sialyl Le(x) antigen showed the highest tumor specificity compared to other antigens. In three normal mucosal specimens and four carcinomas with Le(a-b-) phenotype, the expression of type 1 antigens (Le(a) and sialyl Le(a)) was not consistent, whereas type 2 antigens (Le(x) and sialyl Le(x)) were consistently observed in carcinomas. The staining of type 1 antigens and Le(x) was decreased in metastatic lesions compared with primary carcinomas, whereas sialyl Le(x) antigen had the same positive-staining rate in both. Metastatic carcinoma expressed the sialylated form more predominantly than the non-sialylated form in type 2 antigens whereas the opposite result was observed in type 1 antigens. These results suggested that: (a) sialyl Le(x), defined by monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen in colorectal carcinoma, and (b) the alteration of Lewis-related carbohydrate antigens in cancer cell membranes, including sialylation and/or aberrant glycosylation, may be related to metastatic behavior. more...

Sialylated carbohydrate antigens, such as CA19-9 (sialyl Lea), CA-50 (sialyl Le4), CSLEX1 (sialyl Lex) and SLX (sialyl Lex-i), were assayed in the same preoperative serum samples of 63 patients with colorectal cancer, and compared with CEA. In addition immunohistochemical expressions of sialyl Lea, sialyl lex and sialyl Lex-i antigens were studied in 62 colorectal carcinomas and 42 normal mucosal sites remote from the malignant lesion using monoclonal antibodies CSLEA1, CSLEX1 and FH-6, respectively, in order to elucidate their tumor-specificity and clinical usefulness as a tumor-associated antigen. Serologically, the percent positive rates of CA19-9, CA-50, CSLEX1, SLX and CEA were 30.2%, 17.7%, 23.8%, 16.1% and 44.4%, respectively. In dukes' A and B, these sialylated carbohydrate antigens, especially CSLEX1 and SLX, showed low positive rates, but the percent positive rates of CSLEX1 and SLX correlated with operative radicality. The positive spectrum of CSLEX1 differed from that of CA19-9 in sera, and CEA had no correlation with these two antigens. The immunohistochemical expression rates of sialyl Lea, sialyl Lex and sialyl Lex-i were 88.1%, 17.0% and 9.5% in normal mucosa, but were 77.8%, 90.5% and 71.4% in carcinoma, respectively. These data suggested that the type 2 chain antigens CSLEX1 and SLX, which have high tumor-specificity compared with CA19-9, may be useful in preoperative diagnosis for extension of carcinoma and operative radicality, although early diagnosis using these sialylated carbohydrate antigens may be difficult, while the combined use of CA19-9, CSLEX1 and CEA should make it possible to detect a wide range of colorectal cancer patients. more...

In forty-one carcinomas and sixteen benign lesions (fibroadenoma and mastopathy) of the human breast, immunohistochemical expression of sialylated and non-sialylated forms of both Lea and Lex, and the A, B, and H type 2 blood group substances were studied by using an indirect immunoperoxidase staining. In normal ductal epithelium and benign lesion of breast, Lewis-related antigens were mostly expressed. Breast carcinomas showed these antigens with the following frequencies: Lea, 31.7% (13/41); sialyl Lea, 56.1% (23/41); Lex, 46.3% (19/41); sialyl Lex, 68.3% (28/41); A/B/H type 2, 38.1% (16/41). Sialylated forms of Lea and Lex were observed more frequently than their respective non-sialylated forms in breast carcinomas. In both one normal epithelium and four carcinomas of breast with Le(a-b-) phenotype, the expressions of type 2 antigens were observed, while type 1 antigens were not consistently expressed. Although compatible expression was observed in all specimens of both normal epithelium and benign lesion of breast, twenty-four cases with the deletion of A and/or B antigens, six cases with H type 2 accumulation and one case with incompatible expression were demonstrated in breast carcinoma. Thirty-one breast carcinomas which showed the deletion of A/B/H type 2 expressed the Lewis-related antigens more frequently than nine cases which showed compatible expression. These results suggested that the activation of terminal fucosyltransferase and sialyltransferase as well as inactivation of some glycosyltransferases had occurred in cancer cell membrane, and sialyl Lex, defined by a new monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen independent of Lewis blood group type in breast cancer. more...

The clinical usefulness as a tumor-associated antigen of the new monoclonal antibody CSLEX1, which reacts with the sialylated LewisX antigen, has been evaluated serologically in 141 patients with a gastric cancer. The serum sialylated LewisX was measured by fluorescent EIA. The percent positive figure of these gastric cancer patients was 17.0% (24/141), which indicates a significant increase when compared with that of the controls. The percent-positive values, according to the clinical stage, were 9.2%, 9.1%, 15.6%, and 36.4% for stages I, II, III, and IV, respectively. The degree of liver metastasis and peritoneal dissemination of the cancer correlated with the percent-positive values of the antigen. This suggests that sialylated LewisX is useful as a tumor-associated antigen. more...

Sialylated Lewis(x) and sialylated Lewis(a) antigens, which are structural isomer each other, were serologically tested to determine the clinicopathological differences and correlation between two antigens, and were also compared with those of serum CEA in 141 patients with gastric cancer. Percent positives in sialylated Lewis(a), CEA and sialylated Lewis(x) showed 26.9%, 21.8% and 17.0% respectively. Percent positive of sialylated Lewis(x) correlated with degree of liver metastasis and peritoneal dissemination. Therefore, it is emphasized that the role of sialylated Lewis(x) is characteristics of detecting a presence of liver metastasis and/or peritoneal dissemination. On the other hand, sialylated Lewis(a) showed high percent positive in cases which had lymph nodes metastasis and mucinous or papillary adenocarcinomas. These two carbohydrate antigens indicated no correlation (r = 0.062) in the spectrum of sera. It is suggested that combination assay of sialylated Lewis(x) and sialylated Lewis(a) is useful in detecting many gastric cancer patients including CEA-negative one. more...

In order to elucidate the factors responsible for evaluation of various tumor markers (CEA, CA-19-9, TPA, Ferritin) in colorectal cancer, correlation between portal blood values of these markers and microangiography of the tumor was examined. 1) Mean values of these markers in portal blood were higher than those in peripheral blood. 2) Microangiography of tumor coincided well with cancer infiltration. A significant extramural vascular change was found in ulcerative cancers which showed a vertical invasion for colonic wall than in those with horizontal invasion or protuberant cancers. 3) The elevated portal CEA was noted in ulcerative cancers with vertical invasion extending through muscular vessels and/or in tumors with vascular disarray and histological necrotic foci. 4) Elevated portal TPA relationship between portal TPA levels and vascular patterns of tumor. 5) Portal CA19-9 levels changed within normal value in correlation with the degree of vascular change. Portal ferritin values showed wide variations as well as peripheral ones. The present study indicates that the extra or intramural vascular change and vascular pattern of tumor may be a major contributing factor to transfer these markers from tumor into blood circulation. more...

Sialyl Lewis(x)-i (SLX) as a new tumor-associated antigen was assayed in sera of 133 gastric cancer and 62 colorectal cancer patients with preoperative state in order to elucidate the clinico-pathological features. The percent positives in sera of patients with gastric and colorectal cancer were 12.7% (17/133) and 16.1% (10/62), respectively, and there were few positive cases in the early stages. Therefore, it is suggested that the early diagnosis for gastric and colorectal cancer using SLX alone may be difficult. However, it is revealed that SLX has a high tumor-specificity in consideration of the clinico-pathological properties such as H, P, n, ly, v factors, depth of cancer invasion and operative radicality. These data suggested that SLX could be applicable as a useful tumor-marker which shows the metastasis or extension of carcinoma. more...