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

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.