Role of tumour markers, cytogenetics

A review is presented on the role of conventional and molecular tumour mark ers (TM) in diagnosis and monitoring of patients with biliopancreatic malig nancies. For biliopancreatic malignancy, following CEA as more historical and basic TM of gastrointestinal diseases, the mainstay marker is CA 19-9 as monosial o-ganglioside/glycolipid and sialyl derivative of lacto-N-fucopentaose II ( sialyl-Lewis(a), hapten of human Lewis(a) bloodgroup determinant). It is de tected 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%-9 5%, sp=72%-90%), biliary (s=55%-79%), hepatocellular and cholangiocellular cancer (s=22%-51%) besides gastric, colorectal and ovarian cancer and occas ionally in lung, breast and uterine cancer. Physiologically elevated concen trations in healthy individuals have to be considered in all sorts of secre tions (e.g. sputum, saliva, bronchial/gastric secretions, bile juice) of in dividuals with Lewis(a)-positive secretor status in contrast with low or la cking serum levels of CA 19-9 in patients with Lewis(a-/b-) status (7%-10% of population). In biliopancreatic malignancies, especially pancreatic canc er, CA 19-9 correlates well with clinical course of disease following surgi cal, 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 clinica l 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) (sialyl lacto-N-tetraose: CA 50, CA 242, Span-1) solely detected by the DUPAN-2 tes t and independent of the Lewis(a) secretor status. Some other markers compr ise in addition to sialyl-Lewis(a) partially the non-sialylated Lewis(a) an tigen (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 us ing molecular markers detecting gene mutations (p53, K-ras), growth factors (EGF, TGF-alpha, TGF-R, HB-EGF, a/bFGFs, KGF) and growth factor receptor a lterations (EGFr, c-erbB2/3/4). From these, K-ras mutations detected in blo od, 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 carcinogenes is, although they are neither yet well established nor standardised by reli able assays. In contrast growth factor and growth factor receptor alteratio ns mainly concerning signal transducing systems seem to reflect increased t umour aggressiveness, thus shorter survival and poorer prognosis thereby co ntributing in the selection of patients for more aggressive therapy.