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Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients

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Abstract

Introduction

Class-III-beta-tubulin (TUBB3) expression may be a potential predictive factor for treatment with microtubule interfering cytotoxic drugs in non-small cell lung cancer (NSCLC). Potential changes in TUBB3 expression during chemotherapy may be of interest if future choice of chemotherapy is to be based on TUBB3 expression. If the biomarker expression changes during chemotherapy, biopsies before initiation of chemotherapy beyond first line may be needed if treatment decision is to be based on TUBB3 expression. Thus, the aim was to explore TUBB3 expression heterogeneity and changes during chemotherapy.

Materials and methods

TUBB3 expression was investigated by immunohistochemistry performed on diagnostic biopsies and on available subsequent resection specimens in 65 NSCLC patients stage T1-3N0-2 who received neoadjuvant carboplatin and paclitaxel (NAC-group). Another group of 53 NSCLC patients stage T1-4N0-1 was treated with surgery alone without preceding chemotherapy (OP-group). Paired repeated samples were compared in order to evaluate for changes in TUBB3 expression.

Results

No statistically significant change in TUBB3 expression was observed between initial diagnostic biopsies and subsequent surgical resections of primary tumors in either the OP-group (p = 0.124) or the NAC-group (p = 0.414). When dichotomized into high and low TUBB3 expression, discordance between diagnostic biopsies and resection specimens of the primary tumors occurred in 22 % and 40 % in the OP-group and NAC-group, respectively (p = 0.169). Significantly more patients having low TUBB3 expression experienced down-staging during neoadjuvant chemotherapy compared to patients having high TUBB3 expression (p = 0.022).

Conclusion

A high degree of discordance of TUBB3 expression between paired repeated tumor samples was observed, which likely reflects intratumoral heterogeneity. This emphasizes a need for optimal tumor tissue samples in order to stratify patients based on TUBB3 expression. No significant changes in TUBB3 expression after neoadjuvant carboplatin and paclitaxel chemotherapy occurred, suggesting no need for rebiopsy in case second-line chemotherapy with microtubule interfering cytotoxic treatments is necessary.

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Acknowledgments

We thank Camilla Cordua Mortensen, Heidi Ugleholdt, and Lone Svendstrup for expert technical assistance. This study was supported by the Danish Cancer Research Foundation, Arvid Nillsons Foundation, Torben and Alice Frimodts Foundation, Aase and Ejnar Danielsens Foundation, Eva and Henry Fraenkels Foundation, The Danish Research Foundation, Snedkermester Sophus Jacobsen and Hustru Astrid Jacobsens Foundation, The Foundation for the Promotion of Medical Cancer Treatment, and The Research Foundation of the Department of Oncology, Rigshospitalet.

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Authors and Affiliations

  1. Department of Oncology, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen, Denmark

    Jan Nyrop Jakobsen & Jens Benn Sørensen

  2. Department of Pathology, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen, Denmark

    Eric Santoni-Rugiu

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  1. Jan Nyrop Jakobsen
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Correspondence to Jan Nyrop Jakobsen.

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Jakobsen, J.N., Santoni-Rugiu, E. & Sørensen, J.B. Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients. Cancer Chemother Pharmacol 73, 43–51 (2014). https://doi.org/10.1007/s00280-013-2315-6

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