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Using Q-RT-PCR to measure cyclin D1, TS, TP, DPD, and Her-2/neu as predictors for response, survival, and recurrence in patients with esophageal squamous cell carcinoma following radiochemotherapy

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to evaluate the use of thymidilate synthetase (TS), thymidilate phosphorylase (TP), dihydropyrimidin dehydrogenase (DPD), Her-2/neu, and cyclin D1 as predictors of therapy response, survival, and recurrence in patients with esophageal squamous cell carcinoma (ESCC) following radiochemotherapy.

Materials and methods

Twenty-six patients with histologically proven intrathoracic, locally advanced ESCC (cT3, cN0/+, cM0) underwent preoperative, combined simultaneous radiochemotherapy followed by R0-transthoracic esophagectomy. Because R0 resection is the strongest known independent prognostic factor in this tumor entity, only R0-resected patients were included in this study. Pre-therapeutically taken, formalin-fixed, and paraffin-embedded tumor biopsies were used for laser-assisted microdissection of tumor cells and RNA extraction and subjected to real-time (TaqMan) quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR).

Results

No significant correlation between clinical or histopathological parameters and the relative gene expression of TS, TP, DPD, or Her-2/neu was observed. However, patients with relative cyclin D1 levels below the median gene expression did not reach median survival compared to the 19.9 months seen in patients with relative cyclin D1 gene expression above the median (P = 0.02). Patients with low cyclin D1 levels experienced significantly less frequent recurrence of the tumor (20% versus 63%; P = 0.006), and there was a significant difference in the recurrence-free interval (P = 0.003).

Conclusions

Despite the small number of investigated patients, our data seem to show that high levels of cyclin D1 measured by real-time Q-RT-PCR before neoadjuvant radiochemotherapy correlate significantly with patient survival, tumor recurrence, and recurrence-free-interval. Cyclin D1 might be useful in identifying patients at high risk of poor prognosis and suffering from recurrence after neoadjuvant radiochemotherapy treatment and R0 resection. Further investigations with a larger cohort are warranted.

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Abbreviations

AUC:

area-under-curve

CTx:

chemotherapy

CI:

confidence interval

DPD:

dihydropyrimidin dehydrogenase

DEPC:

di-ethyl-pyro-carbonate

ESCC:

esophageal squamous cell carcinoma

RTx:

radiotherapy

RTx/CTx:

radiochemotherapy

TS:

Thymidilate synthetase

TP:

Thymidilate phosphorylase

5-FU:

5-fluorouracil

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Acknowledgment

The authors wish to dedicate this manuscript to their distinguished colleague and friend Dr. med. Hans-Joachim Dittler, Department of Surgery, Technical University of Munich, who died in 2007.

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Authors and Affiliations

  1. Department of Surgery, Comprehensive Cancer Center, University of Tübingen, Hoppe-Seyler Strasse 3, 72076, Tübingen, Germany

    Björn L. D. M. Brücher

  2. Department of Pathology, Technical University of Munich, Munich, Germany

    Gisela Keller, Falko Fend, Heinz Höfler & Katja Specht

  3. Department of Pathology, University Hospital of Freiburg, Freiburg, Germany

    Martin Werner & Silke Lassmann

  4. GSF-National Research Center for Environment and Health, Munich, Germany

    Ulrike Müller, Heinz Höfler & Katja Specht

  5. National Cancer Institute of Milan, Milan, Italy

    Antonello Domenico Cabras

  6. Department of Epidemiology & Statistics, Technical University of Munich, Munich, Germany

    Raymonde Busch

  7. Department of Surgery, University of Salzburg, Salzburg, Austria

    Hubert Stein

  8. Department of Internal Medicine, Klinikum Garmisch-Patenkirchen, Munich, Germany

    Hans-Dieter Allescher

  9. Department of Radiotherapy, Technical University of Munich, Munich, Germany

    Michael Molls

  10. Department of Surgery, Technical University of Munich, Munich, Germany

    J. Rüdiger Siewert

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  1. Björn L. D. M. Brücher
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Correspondence to Björn L. D. M. Brücher.

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Brücher, B.L.D.M., Keller, G., Werner, M. et al. Using Q-RT-PCR to measure cyclin D1, TS, TP, DPD, and Her-2/neu as predictors for response, survival, and recurrence in patients with esophageal squamous cell carcinoma following radiochemotherapy. Int J Colorectal Dis 24, 69–77 (2009). https://doi.org/10.1007/s00384-008-0562-5

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