Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors : correlation to tumor histopathology and clinical follow-up

• Published in: International journal of colorectal disease Vol. 21; no. 3; pp. 238 - 247
• Main Authors: LASSMANN, Silke, HENNIG, Michael, ROSENBERG, Robert, NÄHRIG, Jörg, SCHREGLMANN, Joachim, KRAUSE, Friedemann, POIGNEE-HEGER, Manuela, NEKARDA, Hjalmar, HOFLER, Heinz, WERNER, Martin
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-04-2006; Berlin Springer Nature B.V
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Colonic Neoplasms - enzymology; Colonic Neoplasms - genetics; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; Combined Modality Therapy; Dihydrouracil Dehydrogenase (NADP) - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Middle Aged; Predictive Value of Tests; Prognosis; Rectal Neoplasms - enzymology; Rectal Neoplasms - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Thymidine Phosphorylase - genetics; Thymidylate Synthase - genetics; Enzyme; Transferases; Glycosyltransferases; Dehydrogenase; Thymidylate synthase; Histopathology; Messenger RNA; Methyltransferases; Gastroenterology; Rectum; Tumor; Oxidoreductases; Colon; Pentosyltransferases; Thymidine phosphorylase
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-005-0767-9

Evaluation of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) mRNA levels in formalin-fixed, and paraffin-embedded tissues of patients with colorectal cancer and their prognostic and/or predictive value.
Total RNA was isolated from microdissected, formalin-fixed, and paraffin-embedded tissues (controls and tumor) and subjected to quantitative RT-PCR (QRT-PCR) in the LightCycler system. Resulting mRNA levels correlated to tumor histology (n=102) and the clinical follow-up in patients treated by resection alone (n=40) and by resection plus adjuvant 5-FU-based chemotherapy (n=52).
Correlation to histopathological parameters revealed a significant association between tumor stage and the TP mRNA level (T and N category and UICC) as well as the TP:DPD (T and N category and UICC) and TS:DPD (T category) ratio. In addition, tumor differentiation was correlated to the TS mRNA level and the TS:DPD ratio. Finally, the TS:DPD ratio was a prognostic marker for overall survival in patients receiving resection alone (p=0.032). Moreover, a high TP:DPD ratio (>8.1; p=0.002) and, marginally, low DPD (<8.2; p=0.05) mRNA levels significantly correlated to disease-free survival.
We present a novel, standardized approach for TP, DPD, and TS mRNA quantification in archival tissue specimens and applied this to a large series of primary colorectal tumors. Correlations to histopathological parameters and clinical follow-up revealed an association of TP, DPD and TS mRNA expression patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer.