Abnormally-fucosylated haptoglobin: a cancer marker for tumour burden but not gross liver metastasis

Abstract

Summary A previous study has shown that there are high levels of an abnormally-fucosylated form of haptoglobin (FHp) in the blood of cancer patients (Thompson & Turner, 1987b). In this study, we investigated the expression of this substance in serial blood specimens from women with ovarian or breast cancer who were undergoing cytotoxic chemotherapy. The The 27 women who had breast cancer had undergone either a lumpectomy or a mastectomy 6 months to 20 years previously (median 3.5 yr). Twenty-four women still had clinical signs of cancer when specimen collection was started. During the period of collection the major therapies were as follows: Mitoxanthrone (ten women); aminoglutethimide, hydrocortisone, disodium pamidronate (three); aminoglutethimide, hydrocortisone (three); Tamoxifen (two); Cyclophosphamide, 5-fluoruracil, prednisolone (two); Ifosphamide, Doxorubicin (one); Vincristine, prednisolone (one); Vincristine, mitomycin (one); LHRH agonist (one); radiotherapy (one) and two were untreated. Nineteen of the women were previously treated with radiotherapy; 17 of these received Tamoxifen and five had prior treatment with Mitoxanthrone.At least two blood specimens were collected from each ovarian and breast cancer patient (median number three; range two to six) over a period of time that varied (median time = 12 months; range 1-22 months). The time between collections also varied (median = 3 months; range 1-15 months). Seventy-seven and 73 specimens were collected from the ovarian and breast patients respectively. Only one or two specimens were collected from the hepatoma patients.Ovarian and breast cancer patients were assessed when specimens were collected; these assessments were made by clinical examination and appropriate radiological and ultrasound scanning techniques. The patient response to therapy was categorised into three groups; complete response, partial response or stable disease, and progressive disease. Complete response was defined as complete disappearance of all demonstrable disease for at least 4 weeks. Partial response was defined as a reduction (> 50% bidimensional or > 30% unidimensional) in total size of measurable disease, and stable disease was defined as < 50% change (bidimensional) or < 30% (unidimensional) in the total size of the measurable lesions. Progressive disease was defined as a >50% (bidimensional) or >30% (unidimensional) increase in the size of any measurable lesion.The hepatocellular cancers were diagnosed by physical examination combined with radiological and ultrasonic scanning techniques, and confirmed by the histological examination of biopsy material. No information was available for the clinical assessments of the hepatoma patients.

The Prevalence and Nature of Glycan Alterations on Specific Proteins in Pancreatic Cancer Patients Revealed Using Antibody-Lectin Sandwich Arrays

“…This fact points to the possible future usefulness of similar assays for cancer detection as suggested before in studies of fucosylated ␣-fetoprotein (27) and haptoglobin (7,8) for identifying liver and pancreatic cancers. Validation of potential markers will involve studies on larger, blinded sample sets including samples from conditions that might potentially give elevations, such as benign liver diseases and inflammatory states of the pancreas.…”

“…Lectins have been valuable in immunoaffinity electrophoresis and blotting methods to identify cancer-associated glycan variants on major serum proteins such as ␣-fetoprotein (6), haptoglobin (7,8), ␣ 1 -acid glycoprotein (9), and ␣ 1 -antitrypsin (10). Antibodies raised against particular glycan groups, such as the Thomsen-Friedenreich antigens (11), the Lewis blood group structures (12), and underglycosylated MUC1 1 (13) also have been used to study the roles of glycans in cancer.…”

Changes of Serum Glycoproteins in Lung Cancer Patients

“…HpA2 isoform (number 9) was significantly up regulated while other two isoforms remained unchanged ( Figure 1 & Figure 2). These alterations might be a result of changes in fucosylation in cancer that are correlated with an increase in the activity of α-(1-3)-fucosyl transferase in the blood (Thompson et al, 1991). Our findings indicate that the alterations of HpA2 occur not only in its level but also its whole pattern in the 2-D gel, which may play an important role in lung tumorigenesis (Maciel et al, 2005).…”

The Detection and Discovery of Glycan Motifs in Biological Samples Using Lectins and Antibodies: New Methods and Opportunities

“…For example, researchers used lectins to identify cancer-associated glycan variants on the serum proteins alpha-fetoprotein ( K. Shimizu et al, 1996 ), haptoglobin ( Okuyama et al, 2006 ; Thompson, Cantwell, Cornell, & Turner, 1991 ), a-1-acid glycoprotein (van Dijk, Havenaar, & Brinkman-van der Linden, 1995), and a-1-antitrypsin ( Thompson, Guthrie, & Turner, 1988 ).…”