title: Role of tumour markers, cytogenetics.
abstract: A review is presented on the role of conventional and molecular tumour markers (TM) in diagnosis and monitoring of patients with biliopancreatic malignancies. For biliopancreatic malignancy, following CEA as more historical and basic TM of gastrointestinal diseases, the mainstay marker is CA 19-9 as monosialo-ganglioside/glycolipid and sialyl derivative of lacto-N-fucopentaose II (sialyl-Lewis(a), hapten of human Lewis(a) bloodgroup determinant). It is detected in serum of healthy individuals at low concentration < 40 U/ml, with lower and often transitional elevation in benign hepatobiliary diseases and with highest levels in excretory ductal pancreatic adenocarcinoma (s = 70%-95%, sp = 72%-90%), biliary (s = 55%-79%), hepatocellular and cholangiocellular cancer (s = 22%-51%) besides gastric, colorectal and ovarian cancer and occasionally in lung, breast and uterine cancer. Physiologically elevated concentrations in healthy individuals have to be considered in all sorts of secretions (e.g. sputum, saliva, bronchial/gastric secretions, bile juice) of individuals with Lewis(a)-positive secretor status in contrast with low or lacking serum levels of CA 19-9 in patients with Lewis(a-/b-) status (7%-10% of population). In biliopancreatic malignancies, especially pancreatic cancer, CA 19-9 correlates well with clinical course of disease following surgical, chemo- or radiotherapy by a quick normalisation within 2-4 weeks after complete surgery, a transient decrease with successful palliative therapy and an often anticipated increase (lead time up to 6 months) before clinical detection in case of relapse or progressive disease. From CA 19-9 related TM tests some are detecting in addition to sialyl-Lewis(a) (sialyllacto-N-fucopentaose II) also the non-fucosylated precursor sialyl-Lewis(c) (sialyllacto-N-tetraose: CA 50, CA 242, Span-1) solely detected by the DUPAN-2 test and independent of the Lewis(a) secretor status. Some other markers comprise in addition to sialyl-Lewis(a) partially the non-sialylated Lewis(a) antigen (CA 195, CAM 43, CA 494) or are less related (CAM 17.1). The initial phase of screening and early detection is hoped to be better assessed by using molecular markers detecting gene mutations (p53, K-ras), growth factors (EGF, TGF-alpha, TGF-beta, HB-EGF, a/bFGFs, KGF) and growth factor receptor alterations (EGFr, c-erbB2/3/4). From these, K-ras mutations detected in blood, stool and bile juice of patients at risk for pancreatic cancer seem to be more promising than p53 alterations as a more later step in carcinogenesis, although they are neither yet well established nor standardised by reliable assays. In contrast growth factor and growth factor receptor alterations mainly concerning signal transducing systems seem to reflect increased tumour aggressiveness, thus shorter survival and poorer prognosis thereby contributing in the selection of patients for more aggressive therapy.
authors.affiliation: Medical Department II, Klinikum Grosshadern, University of Munich, Germany. lamerz@med2.med.uni-muenchen.de
authors.forename: R
authors.initials: R
authors.lastname: Lamerz
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018395:CA-19-9 Antigen / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002869:Chromosome Aberrations; D004260:DNA Repair / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; C074601:CA 242 antigen; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen