Okoń Krzysztof, Klimkowska Agnieszka, Wójcik Piotr, Osuch Czesław, Papla Bolesław, Stachura Jerzy
Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Krakow.
Pol J Pathol. 2006;57(1):29-33.
Colorectal carcinoma is etiopathologically heterogenic. It may develop through a sequence of mutations leading to chromosome instability or be a result of defects in DNA repair mechanisms manifested by microsatellite instability. Carcinomas of this type are supposed to be characterized by a better prognosis and a different response to chemotherapy. The main target of 5-fluorouracil (5-FU) treatment is thymidylate synthase (TS). High TS expression has been identified as promoting resistance to 5-FU. The objective of the present investigation was to determine whether microsatellite instability is associated with thymidylate synthase expression. Ninety-eight cases of colorectal carcinoma were studied. Microsatellite instability was evaluated in frozen material employing the PCR reaction with gel and capillary electrophoresis. TS expression levels were assessed in preparations stained immunohistochemically using a semiquantitative method on a scale with scores from 0 to 3. The MSI-H phenotype was detected in ten cases, MSI-L in 16, and MSS in 72. The mean TS expression score was 1.79. In the MSS group, the mean TS expression score was 1.69, in the MSI-L group the mean TS expression score was 1.73, and in the MSI-H group the mean TS expression score was 2.67. The differences between MSI-H and MSS/MSI-L were statistically significant (p<0.0002 and p<0.004, respectively). The results may explain the different response of MSI-H carcinomas to 5-FU treatment.
结直肠癌在病因病理上具有异质性。它可能通过一系列导致染色体不稳定的突变发展而来，或者是由微卫星不稳定所表现出的DNA修复机制缺陷导致的。这种类型的癌症被认为具有较好的预后以及对化疗的不同反应。5-氟尿嘧啶（5-FU）治疗的主要靶点是胸苷酸合成酶（TS）。高TS表达已被确定为促进对5-FU的耐药性。本研究的目的是确定微卫星不稳定是否与胸苷酸合成酶表达相关。对98例结直肠癌病例进行了研究。采用凝胶和毛细管电泳的PCR反应在冷冻材料中评估微卫星不稳定。使用半定量方法在免疫组织化学染色的制剂中评估TS表达水平，评分范围为0至3。检测到10例为微卫星高度不稳定（MSI-H）表型，16例为微卫星低度不稳定（MSI-L），72例为微卫星稳定（MSS）。TS表达的平均评分为1.79。在MSS组中，TS表达的平均评分为1.69，在MSI-L组中平均评分为1.73，在MSI-H组中平均评分为2.67。MSI-H与MSS/MSI-L之间的差异具有统计学意义（分别为p<0.0002和p<0.004）。这些结果可能解释了MSI-H癌症对5-FU治疗的不同反应。
