4.1 Article

High thymidine kinase 1 (TK1) expression is a predictor of poor survival in patients with pT1 of lung adenocarcinoma

Journal

TUMOR BIOLOGY
Volume 33, Issue 2, Pages 475-483

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-011-0276-0

Keywords

Lung adenocarcinoma; Thymidine kinase 1; Stromal invasion; Immunohistochemistry; Survival

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Funding

  1. Nanjing Jinling Hospital, Nanjing University Medical School, China
  2. Cancer Society of Stockholm
  3. Faculty of Karolinska Institute, Clinical Research Center, Karolinska University Hospital
  4. Swedish International Development Cooperation Agency, Stockholm, Sweden
  5. Swedish Research Council

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In this study, we explore the association of thymidine kinase 1 (TK1) expression in tumour tissues with clinical pathological parameters and prognosis in patients with pathological T1 (pT1) lung adenocarcinoma. The expression of TK1 was studied by immunohistochemistry techniques in 80 patients with surgically resected pT1 lung adenocarcinoma, retrospectively and at > 10-year follow-up. Compared to patients with low TK1 expression [labelling index (LI) < 25.0%], patients with high TK1 expression (LI a parts per thousand yen25.0%) showed significantly increased lymphatic/vascular permeation and lymph node involvement and higher stromal invasion grade and pathological stage, and a greater number of patients had a tumour size of 2.1 to 3.0 cm. The 5-year survival and the mortality during follow-up for patients with high TK1 expression were significantly worse than that of patients with low TK1 expression. The prognoses of the cases with grade 0, grade 1 and grade 2 stromal invasions were similar and were better than those of cases with grade 3. In patients with stromal invasion grade 3, the 5-year survival and the mortality during follow-up were significantly worse for patients with high TK1 compared to patients with low TK1 expression. Univariate analyses showed that stromal invasion and TK1 expression were significant prognostic factors, while in the multivariate analysis, TK1 expression and tumour stage were found to be independent prognostic factors, but not stromal invasion. This is the first study showing that TK1 expression in combination with stromal invasion is a more reliable prognostic factor than stromal invasion classification itself in patients with pT1 lung adenocarcinoma. TK1 expression enables a further classification of the patients and opens opportunities for improved treatment outcome.

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