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ABSTRACTS of the 13Th INTERNATIONAL HAMBURG SYMPOSIUM on TUMOR MARKERS

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ABSTRACTS of the 13Th INTERNATIONAL HAMBURG SYMPOSIUM on TUMOR MARKERS ANTICANCER RESEARCH 25: 4773-4848 (2005) ABSTRACTS OF THE 13th INTERNATIONAL HAMBURG SYMPOSIUM ON TUMOR MARKERS 27 - 29 November, 2005 Hamburg, Germany Edited by R. Klapdor Abstracts of the 13th International Hamburg Symposium on Tumor Markers, 27 - 29 November 2005 Gastroenterology Materials and Methods: The log-rank test and Wilcoxon test were used for statistical evaluation. Survival analysis was computed by the Kaplan-Meier method. Serum levels of 1 tumor markers conventionally used in routine clinical praxis TUMOR MARKERS IN LIVER TUMORS (CA19-9, CEA, C724) were studied. Also taken into account were markers offering information about the proliferation R. Lamerz1, P. Stieber2 activity of malignancies (TK, TPA, TPS). Cut-off values were obtained from previous studies (reference group 1Medizinische Klinik II, 2Inst. f. Klinische Chemie, Campus- included patients with clinical remission). Grosshadern, Klinikum der Ludwig-Maximilians- Results: One hundred and nine patients, who underwent Universität, München, Germany explorative laparotomy without any surgical therapy between September 1999 and June 2005, were studied (16 On suspicion of liver tumors by symptoms or altered patients with hepatocellular carcinoma, 5 with laboratory values, the detection of one or more liver foci by cholangiocellular carcinoma, 25 with gall bladder ultrasound represents a serious initial situation. This carcinoma, 51 with colorectal liver metastases, 6 with requires multi-fold procedures to ascertain diagnosis and, in metastases of mammary gland carcinoma, 2 with metastases case of cancer, the differential diagnosis between primary of melanoblastoma, 1 with metastases of stomach carcinoma liver cancer or secondary metastases. Among primary liver and carcinoid, 2 patients with metastases of unknown tumors, hepatocellular carcinoma (HCC) represents the origin). One hundred explorative laparotomies and 9 most frequent tumor with typical high-risk prior diseases laparoscopic operations were performed. Twenty patients such as chronic liver diseases due to hepatitis B and C and had undergone other liver operations before and belonged chronic alcohol abuse. Among the recommended, e.g. semi- to the group planned for reoperation for relapse of disease. annual, follow-up procedures, imaging by steadily improving Conclusion: The results of this pilot study suggest the technology is increasingly superior to other procedures such importance of tumor markers for prediction of short as tumor markers. In an overview, the multiple investigated survival rate. These markers could be used as a suitable tumor markers in HCC, including the most relevant markers supplement to classic clinical, laboratory and radio- (AFP, AFP-L3 lectin subtype, DCP, glypican-3), are diagnostic parameters. They seem to be very helpful for presented and described as adjuncts for HCC screening in planning of palliative oncological therapy for patients with high-risk patients, for prognosis, diagnosis, aftercare, liver malignancies, that could not be treated by surgical detection of recurrence and efficient control of therapy therapy. The correlation between early recurrence and response, according to recommendations by EASL, EGTM increased proliferative activity of liver malignancy in the and NACB. preoperative period and an increased tendency of colorectal liver metastasis to earlier recurrence than non-colorectal liver metastasis was proved. 2 ARE TUMOR MARKERS USEFUL FOR PREDICTION OF SURVIVAL RATE AFTER 3 EXPLORATIVE LAPAROTOMY FOR LIVER VALUE OF p53 AUTOANTIBODIES AND CA 242 IN MALIGNANCIES? PATIENTS WITH PANCREATIC CARCINOMA V. Liska1, L. Holubec Jr.2, V. Treska1, T. Skalicky1, Ch. Hansen, J. Raedle, H. Sauer-Eppel, G.M. Oremek A. Sutnar1, S. Kormunda3, O. Topolcan2 Zentrum Innere Medizin, Klinikum der Johann Wolfgang 1Department of Surgery, 2Department of Oncology, Goethe Universität, Frankfurt am Main, Germany University Hospital Pilsen; 3Section of Medical Statistics, Medical Faculty Pilsen, Charles University Prague, Czech In human pancreatic carcinoma (PCa), mutations in the p53 Republic tumour suppressor gene are present in up to 50% of cases. Conformational change and cellular accumulation, together Objective: Tumor markers are used for prediction of relapse with subsequent release of mutant and normal p53 protein and the effects of postoperative or postoncological therapy from transformed cells, may initiate a B-cell response with as a standard of follow-up. The metastatic process of the the generation of circulating autoantibodies to p53 protein liver and primary malignancies of the liver and gall bladder (anti-p53). The sera of 85 consecutive patients with acute are very common diseases in Europe. pancreatitis (n=19), chronic pancreatitis (n=33) and PCa 4775 ANTICANCER RESEARCH 25: 4773-4848 (2005) (n=33) were analyzed to evaluate the specificity of limited in their clinical usefulness. The most promising results autoantibodies to p53 protein (anti-p53) as a serological have been observed with Tumor-M2PK measurements. marker for PCa. Detection of anti-p53 was performed using Concerning CRC, the overall sensitivity of M2PK was around an ELISA system with immobilized recombinant wild-type 77.9% in several clinical studies. The overall sensitivity for p53 protein. Autoantibodies to p53 were detectable in 1/19 adenomas was 45.9%, increasing to 61.1% for adenomas >1 patients with acute (5.3%) and in 4/33 patients with chronic cm. Specificity ranged from 74.3-83.3% in recent reports in pancreatitis (12.1%). All anti-p53-positive patients with patients undergoing colonoscopy. However, according to results acute or chronic pancreatitis were carefully examined and obtained in a health care check up setting of more than 1000 no underlying malignant disease was found. persons, the specificity must be expected to be about 95%. During follow-up (range: 281 – 647 days; mean: 472 days) Conclusion: The measurement of Tumor-M2PK in stools none of these patients showed any evidence of subsequent seems to be the most promising tool for CRC screening at development of PCa or any other malignant disease. In present. In combination with colonoscopy for positive test patients with PCa, anti-p53 was detected in 8/33 cases results, this marker can characterize patients at high-risk at resulting in a sensitivity of 24% with a specificity of 90%. In reasonable cost. This test should, therefore, be recommended contrast to anti-p53, detection of serum carbohydrate for screening programs. antigen (CA 242) resulted in a sensitivity and specificity of 66% and 80% (CA 242<27 U/ml) and 80% and 90% (Ca 242>100 U/ml) for the detection of PCa, respectively. 5 Taken together, the sensitivity of anti-p53 formation was DISEASE PROGRESSION AND TUMOR STAGE IN low in patients with PCa (24%). Furthermore, the detection COLORECTAL CANCER CORRELATE WITH CEA of anti-p53 was not specific for malignancy, indicating that AND EGFR GENE EXPRESSION IN DISSEMINATED severe inflammatory processes may also induce anti-p53 TUMOR CELLS formation. V. Zieglschmid, C. Hollmann, W. Albert, O. Böcher 4 AdnaGen AG, Langenhagen, Germany FECAL PYRUVATE KINASE M2 (TUMOR-M2PK) MEASUREMENT: A NEW SCREENING CONCEPT Disease progression and tumor stage in colorectal cancer FOR COLORECTAL CANCER (CRC) WITH patients was correlated with tumor-associated gene PROMISING PERSPECTIVES expression in disseminated tumor cells (DTC) to evaluate the clinical utility of DTC detection and the expression of N. Ewald, M. Schaller, M. Bayer, A. Akinci, R.G. Bretzel, tumor-associated genes with respect to individual patient H.U. Klör, P.D. Hardt prognosis and monitoring of therapy. Materials and Methods: A DTC detection assay, consisting Third Medical Department, Giessen University Hospital, of immunomagnetic enrichment and expression analysis of Germany the tumor-associated genes CEA, EGFR and GA733-2, was developed to analyze a total of 196 peripheral blood Colorectal cancer (CRC) is a disease with major impact on samples collected from 76 patients with Dukes’ A, B, C and both public health and public health costs. Colonoscopy is D tumor stage in a multicenter study. Tumor-associated currently supposed to be the best screening tool for CRC. gene expression in metastatic patients was compared with However, acceptance in the population is very poor: the results in patients with Dukes’ A, B and C tumor stage although it has been included in screening programs in the assessed prior to surgery and post surgery. CEA mRNA German health system since 2002, only about 1.7% have expression was compared with CEA serum protein levels. been enrolled. Therefore, the evaluation of additional Results: Prior to surgery, EGFR and CEA expressions screening tools is of great interest. Recently, testing for fecal were assessed in 88% (p=0.001) and 0% (p=0.002), post occult blood (FOBT), genetic alterations or alterations in surgery in 66% (p=0.001) and 20% (p=0.002), as well as in tumor metabolism (e.g. tumor-M2PK) have been under 15% (p<0.0001) and 66% (p<0.0001) of blood samples investigation. collected from metastatic patients in a comparison analysis, FOBT has been included in screening programs around the respectively. Prior to surgery and in follow-up samples, an world and proved a certain benefit, however, the performance expression of tumor-associated genes in DTC indicated an of this marker is rather poor. Testing for genetic alterations (K- ongoing metastatic process. There was no correlation ras, p53 etc.) is very interesting, however DNA isolation between DTC expressing
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