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Unexpected Immunohistochemical Localization of Deoxycytidine Kinase

Cross Ca ncer Institute and Department of Oncology, University of Alberta, Edmonton, Alberta, Canada

To the Editor:

We read with great interest the April 15, 2006 article by Sebastiani et al. reporting immunohistochemical evaluation of deoxycytidine kinase (dCK) in 44 pancreatic cancer patients, which found that most cases (40 of 44) were positive for dCK (1). Based on the observed staining, the investigators have shown low dCK expression to be significantly associated with higher age (P < 0.0006), female sex (P < 0.04), and most importantly, decreased overall survival of patients (P < 0.0009) and suggest that pretreatment dCK might be a predictive factor for benefit from gemcitabine. We were surprised, however, to read that positive dCK staining was predominantly nuclear, as the reported literature supports a cytoplasmic cellular localization on the basis of immunochemistry, immunoblotting of cellular fractions, enzymatic activity studies, and kinetic isotope incorporation experiments (2–9).

This finding is particularly surprising because Sebastiani et al. used the same rabbit polyclonal antibody reported previously to show cytoplasmic localization of dCK in cell lines, thymocytes, and splenocytes (4) and in various cultured hematologic cells (2). In these studies, nuclear staining has been reported only in cells with very high levels of dCK protein (2, 4). Given the unexpected cellular localization and the possibility for antibody cross-reactivity with non-dCK epitopes in antigen-retrieved formalin-fixed sections, we wonder whether additional controls might further clarify this important study.

References

1. Sebastiani V, Ricci F, Rubio-Viquiera B, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res 2006;12:2492–7.[Abstract/Free Full Text]
2. Hubeek I, Peters GJ, Broekhuizen AJ, et al. Immunocytochemical detection of deoxycytidine kinase in haematological malignancies and solid tumours. J Clin Pathol 2005;58:695–9.[Abstract/Free Full Text]
3. Arner ES, Eriksson S. Mammalian deoxyribonucleoside kinases. Pharmacol Ther 1995;67:155–86.[CrossRef][Medline]
4. Hatzis P, Al-Madhoon AS, Jullig M, Petrakis TG, Eriksson S, Talianidis I. The intracellular localization of deoxycytidine kinase. J Biol Chem 1998;273:30239–43.[Abstract/Free Full Text]
5. Keszler G, Spasokoukotskaja T, Csapo Z, et al. Activation of deoxycytidine kinase in lymphocytes is calcium dependent and involves a conformational change detectable by native immunostaining. Biochem Pharmacol 2004;67:947–55.[CrossRef][Medline]
6. Spyrou G, Reichard P. Compartmentation of dCTP pools. Evidence from deoxyliponucleotide synthesis. J Biol Chem 1987;262:16425–32.[Abstract/Free Full Text]
7. Spyrou G, Reichard P. Intracellular compartmentation of deoxycytidine nucleotide pools in S phase mouse 3T3 fibroblasts. J Biol Chem 1989;264:960–4.[Abstract/Free Full Text]
8. Spasokukotskaja T, Spyrou G, Staub M. Deoxycytidine is salvaged not only into DNA but also into phospholipid precursors. Biochem Biophys Res Commun 1988;155:923–9.[CrossRef][Medline]
9. Spasokukotskaja T, Taljanidisz J, Sasvari-Szekely M, Staub M. Deoxycytidine is salvaged not only into DNA but also into phospholipid precursors. III. dCOP-diacylglycerol formation in tonsillar lymphocytes. Biochem Biophys Res Commun 1991;174:680–7.[CrossRef][Medline]

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