TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy
TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy
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DOI：
10.1002/jso.22123
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发表时间：
2012-05-01
影响因子：
2.5
通讯作者：
Kusunoki, Masato
中科院分区：
文献类型：
--
作者：
Tanaka, Koji;Saigusa, Susumu;Kusunoki, Masato
背景与目的：在接受以5-氟尿嘧啶(5-FU)为基础的放化疗(CRT)的直肠癌患者中，约有20%的患者在手术后发生远处转移复发。本研究旨在探讨5-FU代谢酶在治疗后标本中的表达水平，并评价其对CRT术后远期复发的预测价值。方法：对40例直肠癌患者行以5-FU为基础的CRT并手术治疗。显微解剖后，从福尔马林固定石蜡包埋标本(FFPE)中提取残留癌组织总RNA。用实时定量逆转录聚合酶链式反应检测胸苷合成酶(TS)、二氢嘧啶脱氢酶(DPD)、胸苷磷酸化酶(TP)和5-FU代谢酶--5-FU磷酸核糖转移酶(OPRT)。结果：与34例无复发者(34例)相比，6例远处复发者TS(P0.01)、DPD(P0.02)和TP(P0.01)显著升高。高TS、DPD和阳性淋巴结转移(PN)是DFS的预后不良因素(TS：P<；0.01，DPD：P<；0.01，PN：P<；0.05)。结论：FFPE标本中TS和DPD的高水平可能预示着直肠癌术后5-FU放疗后的远期复发。5-FU代谢酶在残留癌组织中的表达分析可能有助于这些患者的治疗分层和临床管理。J·奥科尔外科医生。2012年；105：529-534。(C)2011年威利期刊公司。
Background and Objectives Distant metastatic relapse occurs in approximately 20% of rectal cancer patients treated with 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) followed by surgery. This study aimed to investigate mRNA level of 5-FU metabolizing enzymes in post-treatment specimens and to evaluate their predictive value of distant recurrence after CRT.Methods: Forty patients with rectal cancer underwent 5-FU-based CRT followed by surgery. After microdissection, total RNA of residual cancer was isolated from formalin-fixed paraffin-embedded (FFPE) specimens. Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT) as 5-FU metabolizing enzyme were measured using real-time reverse transcription polymerase chain reaction.Results: Patients (n 6) who developed distant recurrence had a significantly higher TS (P 0.01), DPD (P 0.02), and TP (P 0.01) levels, compared with those patients (n 34) without recurrence. High TS, DPD, and positive lymph node metastasis (pN) were significantly poorer prognostic factors for DFS (TS: P < 0.01, DPD: P < 0.01, pN: P < 0.05).Conclusions: High TS and DPD mRNA levels on FFPE specimens may predict distant recurrence of rectal cancer treated with 5-FU-based preoperative CRT followed by surgery. Expression analysis of 5-FU metabolizing enzyme in residual cancer may be useful for treatment stratification and clinical management in these patients. J. Surg. Oncol. 2012; 105: 529-534. (C) 2011 Wiley Periodicals, Inc.