Cancer-associated Carbohydrate Research Articles

Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous effusions from patients diagnosed with epithelial ovarian carcinoma: Evidence of up-regulated Tn and Sialyl Tn antigen expression in effusions

The object of this study was the investigation of carbohydrate antigen expression in malignant epithelial cells and benign mesothelial cells in serous effusions from patients diagnosed with epithelial ovarian carcinomas. In addition, to compare antigen expression in carcinoma cells in effusions with those of corresponding primary tumors and metastatic lesions. Sections from 63 malignant effusions from ovarian carcinoma patients and 15 reactive effusions were immunohistochemically stained, using 5 monoclonal antibodies for Lewis y, Sialyl Lewis x, Tn, and Sialyl Tn antigens. Tissue sections ( n = 97) from corresponding primary ovarian carcinomas and metastatic lesions, as well as from 12 malignant mesotheliomas, were additionally stained using the above panel. Staining for the 4 antigens was seen in carcinoma cells in serous effusions in the majority of cases (range = 71% to 85%). In contrast, immunoreactivity was detected in mesothelial cells in only 6% to 23% of the specimens studied ( P < .001 for all 5 markers). With the exception of B3 antibody against Lewis y antigen, malignant mesotheliomas stained negative, infrequently showing focal immunoreactivity. An up-regulation of Tn and Sialyl Tn expression was detected in carcinoma cells in effusions when compared with both primary tumors ( P < .003 and P < .007, respectively) and metastatic lesions ( P < .034 and .041, respectively). Cancer-associated carbohydrate antigens can thus be used as an adjunct in the differentiation between malignant epithelial and reactive mesothelial cells. Ovarian carcinoma cells in effusions show up-regulation of Tn and Sialyl Tn, possibly representing a transient phenotypic alteration facilitating metastasis. H UM P ATHOL 31: 1081-1087.

High serum concentrations of sialyl Tn antigen in carcinomas of the biliary tract and pancreas.

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.

Thomsen-Friedenreich and its precursor (Tn) antigen expression in normal skin and in benign cutaneous tumours: a marker for sebaceous differentiation.

The Thomsen-Friedenreich (T) antigen is the core disaccharide of cancer-associated carbohydrates, whose expression allegedly correlates with the prognosis of some carcinomas. We studied the expression of the T antigen and its precursor (Tn) with monoclonal antibodies in formalin-fixed specimens of normal skin and various benign cutaneous tumours and inflammatory lesions (n: 105). In normal skin, both antigens were consistently expressed within the cytoplasm of mature sebocytes and rarely over the luminal surface of secretory sweat gland cells. All (21/21) sebaceous tumours showed strong T/Tn positivity; several (9/16) sweat-gland tumours were also immunoreactive, although more weakly. Pilar (n = 11), non-adnexal tumours (n = 45) and inflammatory lesions (n = 12) were as a rule unreactive. These results suggest that the T antigen is a sensitive marker of sebaceous differentiation that can be used for the study of adnexal skin tumours in routinely processed tissue specimens.

CA19‐9 as a predictor of recurrence in patients with colorectal cancer

Background and Objectives CA19-9 is a cancer-associated carbohydrate antigen that plays a role in the process of tumor progression as an adhesion molecule. Methods We evaluated the prognostic value of CA19-9 tumor expression and CA19-9 preoperative and postoperative serum levels in colorectal cancer patients treated by complete resection. The most powerful discrimination was achieved using the three CA19-9 markers in combination. Results CA19-9 tumor expression was identified by immunostaining in 71.0% (86/121) of primary carcinomas. Positive CA19-9 serum levels (≥37 U/ml) were restricted to cases with positive tumor expression, and CA19-9 was detected more frequently in preoperative serum (20.6%, 25/121) than in 1-month postoperative serum (6.6%, 8/121). Positive tumor expression, positive preoperative serum level, and positive postoperative serum level were all predictive of increased cancer mortality. Patients with three negative parameters had no recurrences and 97.1% 5-year survival, whereas patients with three positive parameters had 62.5% recurrence and 42.8% 5-year survival. Conclusions CA19-9 detection in tumor tissue and serum identified patients at high risk of cancer recurrence and death and may be useful in selecting patients for adjuvant therapy. J. Surg. Oncol. 1997;66:238–243. © 1997 Wiley-Liss, Inc.

CA19-9 as a predictor of recurrence in patients with colorectal cancer.

CA19-9 is a cancer-associated carbohydrate antigen that plays a role in the process of tumor progression as an adhesion molecule. We evaluated the prognostic value of CA19-9 tumor expression and CA19-9 preoperative and postoperative serum levels in colorectal cancer patients treated by complete resection. The most powerful discrimination was achieved using the three CA19-9 markers in combination. CA19-9 tumor expression was identified by immunostaining in 71.0% (86/121) of primary carcinomas. Positive CA19-9 serum levels (> or = 37 U/ml) were restricted to cases with positive tumor expression, and CA19-9 was detected more frequently in preoperative serum (20.6%, 25/121) than in 1-month postoperative serum (6.6%, 8/121). Positive tumor expression, positive preoperative serum level, and positive postoperative serum level were all predictive of increased cancer mortality. Patients with three negative parameters had no recurrences and 97.1% 5-year survival, whereas patients with three positive parameters had 62.5% recurrence and 42.8% 5-year survival. CA19-9 detection in tumor tissue and serum identified patients at high risk of cancer recurrence and death and may be useful in selecting patients for adjuvant therapy.

Different expressions of sialyl Tn antigen between polypoid and flat-type early colorectal cancers

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. 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. 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. 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.

Altered mRNA expression of specific molecular species of fucosyl‐ and sialyl‐transferases in human colorectal cancer tissues

Human colorectal cancers express various cancer-associated carbohydrate determinants such as Lewis Y or sialyl Lewis A, suggesting a considerable alteration in glycosyltransferase activities occurring upon malignant transformation. We investigated the mRNA amounts of fucosyltransferase (Fuc-T) and sialyltransferase (ST) isoenzymes, including Fuc-T III, IV, V, VI and VII and ST-3N, ST-30 and ST-4, in human colorectal cancer tissues by Northern blotting and RT-PCR. Regarding fucosyltransferases, mRNA of Fuc-T III and VI was not significantly altered, and only Fuc-T IV mRNA showed a moderate increase in cancer tissues when compared with adjacent non-malignant colonic epithelia taken from the same patient (273 ± 96%; p < 0.001). The moderate increase of Fuc-T IV message may be related to an enhanced expression of Lewis Y in colon cancer tissues. In the ST isoenzymes, mRNA for ST-3N remained unchanged, whereas that for ST-4 decreased significantly in cancer tissues, to 32 ± 29%, (p < 0.005). The most remarkable finding was that the message of ST-30 was prominently increased in cancer tissues compared with non-malignant colorectal mucosa. When further investigated by quantitative RT-PCR assays on a larger series of patients with colorectal cancers, the average increase in mRNA for ST-30 was 459 ± 200% compared with that in adjacent non-malignant epithelium (significant at p < 0.0001). The increase of ST-30 message was more prominent in the cancer tissues strongly expressing sialyl Lewis A than in the cancer tissues expressing sialyl Lewis A only weakly or moderately (significant at p < 0.05). The marked increase in the message of ST-30 is suggested to be related to an enhanced expression of sialylated carbohydrate determinants in colon cancer tissues including sialyl Lewis A, since the enzyme exhibited a significant activity against the type I chain carbohydrate substrate and produced the precursors for sialyl Lewis A synthesis, when its cDNA was expressed in Cos-7 cells. Int. J. Cancer 71:556-564, 1997 © 1997 Wiley-Liss, Inc.

Altered mRNA expression of specific molecular species of fucosyl- and sialyl-transferases in human colorectal cancer tissues.

Human colorectal cancers express various cancer-associated carbohydrate determinants such as Lewis Y or sialyl Lewis A, suggesting a considerable alteration in glycosyltransferase activities occurring upon malignant transformation. We investigated the mRNA amounts of fucosyltransferase (Fuc-T) and sialyltransferase (ST) isoenzymes, including Fuc-T III, IV, V, VI and VII and ST-3N, ST-30 and ST-4, in human colorectal cancer tissues by Northern blotting and RT-PCR. Regarding fucosyltransferases, mRNA of Fuc-T III and VI was not significantly altered, and only Fuc-T IV mRNA showed a moderate increase in cancer tissues when compared with adjacent non-malignant colonic epithelia taken from the same patient (273 +/- 96%; p < 0.001). The moderate increase of Fuc-T IV message may be related to an enhanced expression of Lewis Y in colon cancer tissues. In the ST isoenzymes, mRNA for ST-3N remained unchanged, whereas that for ST-4 decreased significantly in cancer tissues, to 32 +/- 29%, (p < 0.005). The most remarkable finding was that the message of ST-30 was prominently increased in cancer tissues compared with non-malignant colorectal mucosa. When further investigated by quantitative RT-PCR assays on a larger series of patients with colorectal cancers, the average increase in mRNA for ST-30 was 459 +/- 200% compared with that in adjacent non-malignant epithelium (significant at p < 0.0001). The increase of ST-30 message was more prominent in the cancer tissues strongly expressing sialyl Lewis A than in the cancer tissues expressing sialyl Lewis A only weakly or moderately (significant at p < 0.05). The marked increase in the message of ST-30 is suggested to be related to an enhanced expression of sialylated carbohydrate determinants in colon cancer tissues including sialyl Lewis A, since the enzyme exhibited a significant activity against the type 1 chain carbohydrate substrate and produced the precursors for sialyl Lewis A synthesis, when its cDNA was expressed in Cos-7 cells.

Elevated sialyl Lewis X-i antigen levels in pleural effusions in patients with carcinomatous pleuritis.

The levels of sialyl Lewis X-i antigen (SLX), which is one of the cancer-associated carbohydrate antigens, were evaluated in 83 malignant and 46 benign pleural effusions. SLX levels in pleural effusion due to lung adenocarcinoma were significantly higher than those due to benign diseases (p < 0.0001), lung cancer other than adenocarcinoma (p = 0.0052), and adenocarcinoma originating from other organs (p = 0.0492). According to receiver operating characteristic (ROC) curve analysis, the optimal cut-off level in the discrimination between malignant and benign pleural effusions was 92 U/ml, which gave a sensitivity of 57.1% and a specificity of 77.8%. The cut-off level of pleural effusion in patients with carcinomatous pleuritis might be higher than that of serum (38 U/ml).

Distinct sub-populations of carcinoma-associated MUC1 mucins as detected by the monoclonal antibody 9H8 and antibodies against the sialyl-Lewis a and sialyl-Lewis x epitopes in the circulation of breast-cancer patients

The cancer-associated epitope defined by the monoclonal antibody (MAb) 9H8 was shown to be closely related to the T antigen (Thomsen-Friedenreich antigen) by its sensitivity to 0-glycanase treatment of a mucin glycopeptide known to express this epitope. The reactivity with this glycopeptide increased upon neuraminiclase treatment, and among several MAbs tested for ability to block binding of the 9H8 antibody, the one specific for the T antigen was the most efficient. Out of 41 serum samples from breast-cancer patients, 11 showed elevated levels of the 9H8 epitope, and several sera also showed elevated levels of the cancer-associated carbohydrate epitopes sialyl-Lewis a and sialyl-Lewis x. By the use of antibodies specific for the MUC1 apoprotein (Ma552 and HMFG-2) it could be shown that these epitopes were attached to the MUC1 apoprotein in at least 4 of the cases. By combining antibodies specific to 9H8, sialyl-Lewis a and sialyl-Lewis x in catcher and tracer positions in several types of immunofluorometric assays, it was shown that the 9H8 epitope was rarely co-expressed with sialyl-Lewis a or sialyl-Lewis x epitopes an the same molecule, though all were expressed on MUC1 mucins. In fact, they can be considered as mutually exclusive epitopes, suggesting that these sera contained different populations of MUC1 mucins distinguishable by different sets of oligosaccharides. The existence of mutually exclusive carbohydrate epitopes on different MUC1 mucins in one and the same patient should be taken into account when designing immunoassays exploiting MUC1-reactive antibodies.

Expression of sialyl Lewis(a) as a new prognostic factor for patients with advanced colorectal carcinoma.

Sialyl Lewis(a) antigen (SLA) is considered to be a cancer-associated carbohydrate antigen. A total of 309 surgically resected primary colorectal cancer specimens and 501 associated metastases to regional lymph nodes were analyzed immunohistochemically using a monoclonal antibody (NS19-9) recognizing SLA. The specimens were obtained from 1981 to 1988 at the Department of Surgery, Keio University School of Medicine (Tokyo, Japan). Sialyl Lewis(a) antigen expression was detected in 75.4% (233/309) of the primary tumors and in 78.5% (99/126) of the metastases to regional lymph nodes. Significantly stronger expression was noted in the regional lymph node metastases than in the primary lesions (P = 4.5E-7). Sialyl Lewis(a) antigen expression in the primary tumors correlated significantly with regional lymph node metastasis (P < 0.005), recurrence (P < 0.005), and postoperative survival (P < 0.001) as determined by univariate analysis. Sialyl Lewis(a) antigen expression in the regional lymph node metastases also correlated strongly with recurrence (P < 0.005) and survival (P < 0.01). As determined by multivariate analysis, SLA expression in the primary tumor correlated strongly with recurrence (P = 3.0E-6) and survival (P = 6.9E-3). Sialyl Lewis(a) antigen expression in primary tumors and metastases to regional lymph nodes is a useful marker for evaluating tumor aggressiveness and prognosis in patients with advanced colorectal cancer.

S27.4. Tumor cell transmigration across cultured endothelium and invasion through reconstituted basement membrane in vitro

Sialyl Lewis antigens (sLex/a) are cancer-associated carbohydrate determinants, serve as ligands of the selectin family and are associated with hematogenous metastasis of cancer. So far, the clinicopathologic values of sialyl Lewis x (sLex) and sialyl Lewis a (sLea) in lung cancer have remained controversial. Using immunohistochemistry, the expressions of sLex and sLea antigens, and an airway mucin (MUC5AC) protein, which was supposed to be the major carrying protein of sialyl Lewis moieties, were studied in surgically resected tumor tissues of 61 patients with stages I or II NSCLC. Thirty-two (52.5%) of the 61 studied subjects were found to be positive for expression of sLea, 40 (65.6%) were positive for expression of sLex, and 16 (26.2%) were positive for MUC5AC protein. Both the expression of sLex and MUC5AC were associated with adenocarcinoma subtype. Patients bearing tumors with MUC5AC and/or sLex expression had a higher probability of post-operative distant metastasis. Survival analysis demonstrated that patients bearing tumors with expression of sLex antigen or MUC5AC had shorter overall survival. The multivariate logistic regression showed that age >65 years old (OR = 0.207, 95% CI = 0.075–0.569, P = 0.002), nodal status (OR = 6.575, 95% CI = 2.459–17.583, P < 0.001), and MUC5AC (OR = 5.545, 95% CI = 1.998–15.386, P = 0.001) were independent factors affecting survival. We concluded that the expression of sLex was related to MUC5AC protein, while patients with tumors co-expressing both MUC5AC and sLex antigen had the worst survival.

The Thomsen-Friedenreich antigen-related carbohydrate antigens in human gastric intestinal metaplasia and cancer.

The Thomsen-Friedenreich antigen (T) is the core disaccharide of O-glycosylated complex carbohydrates and is presumed to be a cancer-associated carbohydrate antigen. However, we recently found that the expression of alpha-T and alpha 1-2 fucosyl alpha-T in the gastric surface epithelia was regulated allogeneically. In the present study we addressed their changes in gastric differentiation disorders. Expression of the T-related antigens was studied histochemically with monoclonal antibody MBrl and peanut agglutinin in 22 normal, 14 metaplastic, and 54 cancerous tissues. The sialylated antigens were detected after neuraminidase digestion. Gastric mucins were purified and examined to determine whether they were the carrier molecules of T. Expression of the normal antigens was decreased or not detected in about 80% of both disorders. Neosialylation of the T-related antigens was observed in the goblet cells of all metaplastic tissues. The absorptive cells did not express any T-related antigens. In gastric cancers, blocked synthesis, i.e., precursor accumulation or totally negative expression, was observed in approximately 66% and neosialylation in approximately 40%. The T-related antigens were carried by mucins. We conclude that blocked synthesis of the T-related antigens was found in a cancer-specific manner. Neosialylation was invariably associated with intestinal metaplasia and occasionally with cancer.

Production of Monoclonal Antibodies Recognizing Cancer-Associated Antigens Expressed on Mucin-Type Sugar Chains

To obtain monoclonal antibodies directed to mucin-type sugar chains, mice were immunized with bovine submaxillary mucin (BSM) that had been conjugated with ovalbumin. Conjugation of BSM with ovalbumin enhanced the antigenicity of BSM to about five to ten times that of intact BSM and resulted in the establishment of ten hybridomas, all of which secreted monoclonal antibodies toward BSM. Most of the antibodies secreted by these hybridomas did not react with glycolipids but did react with glycoproteins. Several antibodies lost their reactivity when sialic acid residues were removed from BSM, indicating that these antibodies recognize carbohydrate moieties of mucins. Immunohistochemical studies revealed that three of the antibodies recognized human ovarian cancer-associated carbohydrate antigens. In addition, one of these three antibodies reacted with a human cultured colonic cancer cell line. The protocol described in this paper was effective in producing monoclonal antibodies that recognize mucin-carbohydrates and some of the generated antibodies can be applied to the detection of cancers.

Fucosyltransferase-producing sialyl Le(a) and sialyl Le(x) carbohydrate antigen in benign and malignant gastrointestinal mucosa.

Sialyl Le(a) antigen and sialyl Le(x) antigen are cancer-associated carbohydrate antigens. Previous immunohistologic and immunochemical studies have shown that these antigens are preferentially expressed in gastric cancer and colonic cancer and that they possibly are related to the metastatic potential of the cancer cells. The biosynthesis of these antigens is completed by fucosyltransferases, but it has not been reported how fucosyltransferases control the expression of these carbohydrate antigens concerning the invasive potential of the cancer. The authors established an assay system for measuring the activity of alpha 1-->4 fucosyltransferase (sialyl Le(a) synthase) and alpha 1-->3 fucosyltransferase (sialyl Le(x) synthase) with a high-pressure liquid chromatography system (HPLC). The activity was measured in various parts of normal and cancerous gastric and colonic tissue and compared with the expression of sialyl Le(a), sialyl Le(x), Le(a), and Le(x) antigens determined in a solid-phase enzyme-linked immunosolvent assay (EIA). Sialyl Le(a) synthase was detected in most normal or malignant mucosa of gastric and colonic tissues, regardless of anatomic locations. Sialyl Le(x) synthase activity generally was low in the normal gastric mucosa, whereas the activity was higher in 77% (7 of 9) of gastric cancer tissues than in corresponding normal tissues with enhanced expression of sialyl Le(x) antigen in most patients (5 of 7). In the large intestine, the activity of sialyl Le(a) synthase and sialyl Le(x) synthase was correlated. Although enhanced expression of sialyl Le(x) in colonic cancer was observed in 86% (12 of 14) of all patients, concomitant higher sialyl Le(x) synthase activity than that in normal tissue was observed in only 58% (7 of 12) of patients. The expression of sialyl Le(a) and sialyl Le(x) antigens in the stomach and the colon was not controlled solely by fucosyltransferases but by a more complicated system involving other glycosyltransferases.

Carbohydrate Antigens and Liver Metastasis in Colorectal Cancer

A comparative immunohistochemical study was performed to analyse the expression of cancer-associated carbohydrate antigens by primary and metastatic lesions of colon cancer. We used monoclonal antibodies which reacted with Lea, Lex and Tn as well as their sialylated derivatives. Twenty-one primary lesions in patients without metastasis and 26 primary and metastatic lesions in patients with liver metastasis were studied. Sialyl Lea was expressed by 57% of the primary lesions of patients without metastasis, 65% of the primary lesions of patients with metastasis and 73% of their liver metastases. Sialyl Lex was expressed by 60% of the primary lesions of patients with and without metastasis as well as by approximately 80% of the liver metastases. Sialyl Lea and sialyl Lex showed strong expressions in the liver metastases, significantly greater than in the primary lesions. The findings indicate the increased expressions of sialyl Lea and sialyl Lex to be correlated with liver metastasis of colorectal cancer.

Synthetic Studies on Sialoglycoconjugates 45: Synthesis of 1-Deoxynojirimycin-Containing Oligosaccharides Related to the Cancer-Associated Sialyl-Lewis a Antigen Recognized by Lec-Cams (Selectins)

Abstract Sialyl-Lewis a (sLea), mainly expressed on cancer cells of the digestive organs,2 has been known as an important cancer-associated carbohydrate antigen.3 Very recently, it has been demonstrated4–9 that the (sLea) antigen is one of the possible ligands recognized by selectins, a family of lectin-type cell adhesion molecules (LEC-CAMS). These findings suggest that the (sLea) antigen may be involved in the process of hematogeneous metastasis of cancer cells. 1-Deoxynojirimycin (DNJ) and related compounds have been shown10 not only to be potent inhibitors of a-glycosidases and glycoprotein-processing enzymes, but also to be of potential clinical value as antidiabetic, antineoplastic and anti-HIV agents. In a preceding paper we reported the synthesis of DNJ-containing sialyl-Lewis x antigen which has been identified as a major carbohydrate ligand for leukocyte adhesion on vascular endothelium mediated by selectins. The present paper describes the first synthesis of l-deoxynojirimycin- containing cance...

Diagnostic Significance of Cancer- Associated Carbohydrate Antigen (CA 19-9) Concentrations in Pancreatic Juice

This study evaluated the diagnostic significance of concentrations of the cancer-associated carbohydrate antigen CA19-9 in pure pancreatic juice (PPJ) collected by endoscopic cannulation. We also attempted to elucidate the features and source of the increased CA19-9 concentration found in the pancreatic juice of patients with chronic pancreatitis (CP) by means of immunohistochemical staining. The mean output as well as the mean concentration of CA19-9 in each of the four fractions collected was highest in patients with pancreatic cancer (PC) and also was elevated significantly in patients with CP compared with controls. However, CA19-9 concentrations were not elevated in patients with cholecystolithiasis. When the cutoff value was set as the mean concentration + 2SD of the controls, significantly elevated concentrations of CA19-9 were found in the third fraction (secretory phase) in 90% of the patients with PC and 66% of the patients with CP. Immunohistochemical staining revealed that CA19-9 was expressed more widely in the ductal cells of CP tissues than in those of normal pancreatic (NP) tissues, with CP tissue showing more CA19-9-positive ductal cells per area than NP tissues. In NP tissue, CA19-9 was localized to the apical surface and supranuclear regions (apical type) in all the ductal cells stained by the antigen, while approximately 50% of cases with CP exhibited a cytoplasmic pattern showing a loss of polarity of the antigen expression. Moreover, this cellular localization pattern was more pronounced in the small ducts that had proliferated and aggregated following the destruction of lobules in CP.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer-associated carbohydrates identified by monoclonal antibodies

“New” carbohydrate structures on the surface of or secreted by cancer cells, identified as epitopes by monoclonal antibodies, are reviewed. These structures may represent the accumulation of precursor chains because of decreased acivity of synthesizing enzymes, the production of new oligosaccharides due to increased or aberrant glycosylation of carbohydrate chains, a change in density of carbohydrates on the cell surface, or exposure of chains usually covered by other structures. Alterations in glycolipid synthesis include aberrant fucosylation and/or sialyation of the lacto series, sialylation or fucosylation of the globo series, and sialyation of the ganglio series. Many of these carbohydrate epitopes have become useful for the diagnosis, prognosis, and monitoring of patients with cancer. Some of the important markers include CA 15.3, CA 19.9, CA 50, CA 125, CA 242, MCA, SLEX, etc. Incomplete glycosylation of O-linked mucin oligosaccharide is recognized as the important “cancer antigen” B72.3, which is sialyated Tn. The oligosaccharide components of α-fetoprotein, carcinoembryonic antigen, and epidermal growth factor receptor are also reviewed. In many instances the glycosylation seen in cancer cells or their products reflects patterns seen during normal development. Thus, cancer-associated oligosaccharides are oncodevelopmental in nature. The biologic significance of carbohydrates on cell surfaces is not known, but several possibilities include a role in cell to cell recognition, intracellular processing of glycoproteins, cell activation, and ability of cancer cells to metastasize.

(2) Cancer-associated Carbohydrate Antigens

(2) Cancer-associated Carbohydrate Antigens