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Jakob, C. et al.

Christiane Jakob, Torsten Liersch, Wolfdietrich Meyer, Gustavo B. Baretton, Wolfgang Schwabe, Peter Häusler, Bettina Kulle, Heinz Becker, Daniela E. Aust,

Prognostic value of histologic tumor regression, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase in rectal cancer UICC Stage II/III after neoadjuvant chemoradiotherapy.

Histologic tumor regression (TR) in rectal cancer after preoperative chemoradiotherapy (CT/RT) may be useful as a surrogate end point for early treatment efficacy, but little is known about its prognostic value. The aim of this follow-up study was to evaluate whether TR is able to predict prognosis in rectal cancer patients. Furthermore, the prognostic value of thymidylate synthase (TS)-gene, thymidine phosphorylase (TP)-gene, and dihydropyrimidine dehydrogenase (DPD)-gene expression after neoadjuvant CT/RT was determined. Forty patients with rectal cancer cUICC stage II/III, receiving preoperative 5-fluorouracil (5-FU) based CT/RT were studied for therapy-induced TR and categorized as "responders" or "nonresponders" according to their TR-grade. Posttherapeutical TS-gene, TP-gene, and DPD-gene expression on surgical resection specimens was quantified by TaqMan real-time PCR after microdissection. During a median follow-up of 58 months, cancer recurrence occurred in 28%. A significant correlation was seen between disease-free survival and lymph node status (P<0.001). All patients, who developed cancer recurrence had a posttherapeutical positive lymph node status. The majority of patients with cancer recurrence were "responders" (91%) after CT/RT. There was a significant correlation between posttherapeutical TS-gene expression and cancer recurrence within the subgroup of "responders." TS-gene expression was significantly higher in patients with cancer recurrence than in those, who are disease-free up to date (P=0.028). In conclusion, lymph node status remains the most important prognostic marker in rectal cancer patients, whereas posttreatment TR by itself has no prognostic significance. Furthermore, measurement of posttherapeutical TS-gene expression may help to identify patients at higher risk for cancer recurrence.[1]

References

Prognostic value of histologic tumor regression, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase in rectal cancer UICC Stage II/III after neoadjuvant chemoradiotherapy. Jakob, C., Liersch, T., Meyer, W., Baretton, G.B., Schwabe, W., Häusler, P., Kulle, B., Becker, H., Aust, D.E. Am. J. Surg. Pathol. (2006) [Pubmed]

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