Shirota Yoshinori, Ichikawa Wataru, Uetake Hiroyuki, Yamada Hiroyuki, Nihei Zenro, Sugihara Kenichi
Department of Digestive Surgery, Tokyo Medical and Dental University, Japan.
Ann Surg Oncol. 2002 Jul;9(6):599-603. doi: 10.1007/BF02573898.
Determination of intratumoral dihydropyrimidine dehydrogenase (DPD) is of clinical interest because increased DPD levels can influence the tumor response to 5-fluorouracil-based chemotherapy through increased inactivation of the agent in tumor cells.
DPD messenger RNA (mRNA) levels were evaluated in 80 consecutive patients undergoing surgery for primary colorectal cancer and 12 cases of liver metastasis.
Higher DPD mRNA levels were associated with higher pathologic classification, corresponding to the T categories (r =.267; P =.003). The DPD mRNA level was statistically higher in tumors with microscopic lymph node metastasis than in those without (P =.002). Hence, the DPD mRNA level increased in accordance with Dukes' classification (r =.387; P =.0001). The DPD mRNA level of the liver metastasis from colorectal cancer was significantly higher than that of primary lesions (P =.002). In eight patients, the DPD mRNA level of the liver metastasis was significantly higher than that of the matched primary tumor (P =.017).
Increases of the DPD mRNA level in cancerous tissue seem to reflect tumor progression. High DPD mRNA levels in liver metastasis and advanced colorectal cancer may have clinical importance for 5-fluorouracil-based chemosensitivity.
肿瘤内二氢嘧啶脱氢酶(DPD)的测定具有临床意义,因为DPD水平升高可通过增加肿瘤细胞中该药物的失活来影响肿瘤对基于5-氟尿嘧啶的化疗的反应。
对80例接受原发性结直肠癌手术的连续患者和12例肝转移患者的DPD信使核糖核酸(mRNA)水平进行评估。
较高的DPD mRNA水平与较高的病理分级相关,对应于T分类(r = 0.267;P = 0.003)。有微小淋巴结转移的肿瘤中的DPD mRNA水平在统计学上高于无转移的肿瘤(P = 0.002)。因此,DPD mRNA水平根据Dukes分期而升高(r = 0.387;P = 0.0001)。结直肠癌肝转移的DPD mRNA水平显著高于原发性病变(P = 0.002)。在8例患者中,肝转移的DPD mRNA水平显著高于匹配的原发性肿瘤(P = 0.017)。
癌组织中DPD mRNA水平的升高似乎反映了肿瘤进展。肝转移和晚期结直肠癌中高DPD mRNA水平可能对基于5-氟尿嘧啶的化疗敏感性具有临床重要性。