The influence of the pituitary tumor transforming gene-1 (PTTG-1) on survival of patients with small cell lung cancer and non-small cell lung cancer

Nina Rehfeld, Helene Geddert, Abedelsalam Atamna, Astrid Rohrbeck, Guillermo Garcia, Slawek Kliszewski, Judith Neukirchen, Ingmar Bruns, Ulrich Steidl, Roland Fenk, Helmut E. Gabbert, Ralf Kronenwett, Rainer Haas, Ulrich Peter Rohr

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Background: PTTG-1 (pituitary tumor transforming gene) is a novel oncogene that is overexpressed in tumors, such as pituitary adenoma, breast and gastrointestinal cancers as well as in leukemia. In this study, we examined the role of PTTG-1 expression in lung cancer with regard to histological subtype, the correlation of PTTG-1 to clinical parameters and relation on patients' survival. Methods: Expression of P TTG-1 was examined immunohistochemically on formalin-fixed, paraffin-embedded tissue sections of 136 patients with, small cell lung cancer (SCLC) and 91 patients with non-small cell lung cancer (NSCLC), retrospectively. The intensity of PTTG-1 expression as well as the proportion of PTTG-1 positive cells within a tumor was used for univariate and multivariate analysis. Results: PTTG-1 expression was observed in 64% of SCLC tumors and in 97.8% of NSCLC tumors. In patients with SCLC, negative or low PTTG-1 expression was associated with a shorter mean survival time compared with patients with strong PTTG-1 expression (265 ± 18 days vs. 379 ± 66 days; p = 0.0291). Using the Cox regression model for multivariate analysis, PTTG-1 expression was a significant predictor for survival next to performance status, tumor stage, LDH and hemoglobin. In contrast, in patients with NSCLC an inverse correlation between survival and PTTG-1 expression was seen. Strong PTTG-1 expression was associated with a shorter mean survival of 306 ± 58 days compared with 463 ± 55 days for those patients with no or low PTTG-1 intensities (p = 0.0386). Further, PTTG-1 expression was associated weith a more aggressive NSCLC phenotype with an advanced pathological stge, extensive lymph node metastases, distant metastases and increased LDH level. Multivariate analysis using Cox regression confirmed the prognostic relevance of PTTG-1 expression next to performance status and tumor stage in patients with NSCLC. Conclusion: Lung cancer belong to the group of tumors expressing PTTG-1. Dependent on the histological subtype of lung cancer, PTTG-1 expression was associated with a better outcome in patients with SCLC and a rather unfavorable outcome for patients with NSCLC. These results may reflect the varying role of PTTG-1 in the pathophysiology of the different histological subtypes of lung cancer.

Original languageEnglish (US)
JournalJournal of Carcinogenesis
Publication statusPublished - Jan 20 2006
Externally publishedYes


ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Health, Toxicology and Mutagenesis

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