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Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy

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Abstract

Purpose

Our aim was to investigate whether chemotherapy with 5-FU induces an alteration in the levels of topoisomerase I (topo I) in colorectal neoplastic tissues

Methods

Twenty-five colorectal cancer patients were included in our study; these had undergone surgical resection of the primary tumor, received post-operatively 5-FU-based adjuvant chemotherapy and then suffered from recurrences. In a standard three-step immunohistochemical procedure, a monoclonal antibody to topo I was applied in both specimens from each patient (one from the primary location and a second one from the recurrence). Statistical analysis was subsequently performed.

Results

Malignant cells from the recurrences displayed a statistical significant increase, concerning the levels of topoisomerase I, by comparison with the primary tumors (P = 0.01). The increase in topo I levels did not demonstrate significant correlations with Duke’s stage (Fisher’s Exact Test P value = 0.496), differentiation grade (P value = 0.661), localization (P value = 0.072), patient sex (P value = 0.434), nor with relapse free interval (P value = 0.493). There was a statistically significant relationship between the age of patients and increase in topo I levels (P = 0.011).

Conclusions

Topo I expression may be part of the malignant cells’ phenotype in recurrent colorectal carcinomas, suggesting a potential role for Topo I in the acquisition of a metastatic phenotype. The increase of topo I immunohistochemical status is likely to be attributed to 5-FU and given the fact that high levels of topo I correlate with sensitivity to camptothecin, advanced colorectal cancer patients seem to benefit from topo I targeted anticancer drug therapy.

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Authors and Affiliations

  1. Medical Oncology Unit, Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    P. Gouveris & N. Tsavaris

  2. 1st Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    A. C. Lazaris, T. G. Papathomas, A. Nonni & E. S. Patsouris

  3. Department of Pathology, “Laikon” General Hospital of Athens, Athens, Greece

    V. Kyriakou & J. Delladetsima

  4. 12 Kerkiras Street, Kalamaria, 55133, Thessaloniki, Greece

    T. G. Papathomas

Authors
  1. P. Gouveris
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  2. A. C. Lazaris
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  3. T. G. Papathomas
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  4. A. Nonni
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  5. V. Kyriakou
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  6. J. Delladetsima
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  7. E. S. Patsouris
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  8. N. Tsavaris
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Correspondence to T. G. Papathomas.

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Gouveris, P., Lazaris, A.C., Papathomas, T.G. et al. Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy. J Cancer Res Clin Oncol 133, 1011–1015 (2007). https://doi.org/10.1007/s00432-007-0253-6

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  • DOI: https://doi.org/10.1007/s00432-007-0253-6

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