title: Evaluation of histochemical anthracyclin binding as potential prognostic parameter in small cell lung cancer.
abstract: In the quest to define further prognostic indicators for small cell lung cancer we have combined standard prognostic evaluation of several tissue and serum markers with monitoring the capacity of tumor cells to bind a carrier-immobilized anthracyclin at the time of diagnosis. The prospective study on 150 patients with small cell lung cancer (SCLC) was performed including the performance of immunohistochemical analysis [neuron-specific enolase (NSE), keratin, and vimentin], and serum marker measurements [NSE, carcinoembryonic antigen (CEA), and CYFRA], flanked by compilation of data on clinical staging at the time of diagnosis, cytostatic drug regimen, remission rates, and survival of the patients. As innovative test substance we synthesized and histochemically exploited carrier-immobilized doxorubicin. The cohort includes 108 men and 42 women grouped into stage I (limited disease: 69 patients; median survival: 317 days), stage IIa (extensive disease IIa: 19 patients; median survival: 244 days), and stage IIb (extensive disease IIb: 62 patients; median survival: 202 days). An oat-cell type was diagnosed in 112 patients, an intermediate cell type in 32 patients, and a combined cell type in 6 patients. Immunohistochemically, 123 tumors (82%) were positive for NSE, 75 tumors (50%) positive for keratin, and 26 tumors (18%) positive for vimentin. In 101 tumors (67%) specific intracellular binding of doxorubicin could be detected. Elevated serum levels for CEA and NSE were associated with an unfavorable prognosis of the corresponding patients (CEA, 261 days vs 467 days; NSE, 316 days vs 414 days). 137 patients received chemotherapy (median survival: 356 days) and 13 patients were not treated (median survival: 119 days). The six patients with the combined cell type and other patients with negative tumor specimen concerning the capacity to bind the anthracyclin were subject of a significantly shortened survival period irrespective of the cytostatic regimen (277 days vs. 381 days). Despite the current uncertainty of the biochemical nature of the histochemically detectable binding, the technical feasibility of the given interdisciplinary approach encourages to further pursue the documentation of anthracyclin binding.
authors.affiliation: Department of Pathology, Thoraxklinik, D-69126 Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kayser
authors.forename: G
authors.initials: G
authors.lastname: Kayser
authors.forename: S
authors.initials: S
authors.lastname: Andre
authors.forename: M
authors.initials: M
authors.lastname: Altiner
authors.forename: H
authors.initials: H
authors.lastname: Gabius
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D014408:Biomarkers, Tumor; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000503:physiopathology; D004317:Doxorubicin / Q000378:metabolism*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D004317:Doxorubicin