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.
OBJECTIVE
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.


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.
Brücher
Björn L D M
BL
Department of Surgery, Comprehensive Cancer Center, University of Tübingen, Hoppe-Seyler Strasse 3, 72076, Tübingen, Germany. bjoern.bruecher@med.uni-tuebingen.de
Keller
Gisela
G
Werner
Martin
M
Müller
Ulrike
U
Lassmann
Silke
S
Cabras
Antonello Domenico
AD
Fend
Falko
F
Busch
Raymonde
R
Stein
Hubert
H
Allescher
Hans-Dieter
HD
Molls
Michael
M
Siewert
J Rüdiger
JR
Höfler
Heinz
H
Specht
Katja
K
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D019938:Cyclin D1 / Q000235:genetics*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013939:Thymidine Phosphorylase / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics*
D019938:Cyclin D1; D042943:Dihydrouracil Dehydrogenase (NADP); D018719:Erb-b2 Receptor Tyrosine Kinases; D013939:Thymidine Phosphorylase; D013940:Thymidylate Synthase