High thymidylate synthase expression is typical for sporadic MSI-H colorectal carcinoma.
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.
Okoń
Krzysztof
K
Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Krakow.
Klimkowska
Agnieszka
A
Wójcik
Piotr
P
Osuch
Czesław
C
Papla
Bolesław
B
Stachura
Jerzy
J
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D013940:Thymidylate Synthase / Q000378:metabolism*; D046888:Tissue Array Analysis
D013940:Thymidylate Synthase