title: Evaluation of different markers in non-small cell lung cancer: prognostic value of clinical staging, tumour cell detection and tumour marker analysis for tumour progression and overall survival.
abstract: We compared the prognostic value of routine pathology, cytokeratin-positive (CK+) cells in the bone marrow (BM) and serum tumour markers (TM) in patients with non-small cell lung cancer (NSCLC) at the time of diagnosis with regard to overall survival (OS) and time to progression (TTP). Eighty patients with NSCLC, staged as T2-4, N0-3, M0 (n=52), M1 (n=27), (Mx = 1) were evaluated. Treatment included chemo-radiotherapy with cisplatin/etoposide and subsequent radical surgical resection. There were 23 complete responders, 50 non-responders and 7 patients who died of non-lung cancer causes. The median follow-up was 12 months (range 1-44 months). Besides routine pathology for tissue and BM, CK+ BM cells were detected by immunocytochemistry (IC) and 4 different tumour markers as well as the shedded domain of the oncoprotein Her-2/neu and urokinase plasminogen activator uPA were determined by radio- or enzyme-immunoassay. Patients classified as stage IV and patients with metastases had a significantly lower TTP and OS. No significant correlation was demonstrated for grading, tumour size or number of involved lymph nodes. The tumour marker tissue polypeptide antigen (TPA) and Cyfra 21-1 were the only marker which significantly correlated with OS. Interestingly, routine pathology could not detect minimal residual BM involvement as IC was able to (p=0.0004) and the presence of even a few CK+ cells significantly correlated with reduced OS. Thus, we conclude that the detection of CK+ cells should be added to routine pathology and for tumour marker determination, studies should focus on Cyfra 21-1 and TPA.
authors.affiliation: University of Essen Medical School, Department of Internal Medicine (Cancer Research), West German Cancer Center, Essen, Germany. sabine.kasimir-bauer@uni-essen.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
authors.forename: Norbert
authors.initials: N
authors.lastname: Schleucher
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Rainer
authors.initials: R
authors.lastname: Neumann
authors.forename: Siegfried
authors.initials: S
authors.lastname: Seeber
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D006801:Humans; D053539:Keratin-19; D007633:Keratins / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010960:Plasminogen Activators / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D013997:Time Factors; D019396:Tissue Polypeptide Antigen / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; D007633:Keratins; D010960:Plasminogen Activators; D018719:Erb-b2 Receptor Tyrosine Kinases; D019396:Tissue Polypeptide Antigen; D014568:Urokinase-Type Plasminogen Activator; C102012:antigen CYFRA21.1