TY - JOUR
TI - Markers of drug resistance in relapsing colon cancer
AU - Lazaris, AC
AU - Kavantzas, NG
AU - Zorzos, HS
AU - Tsavaris, NV and
AU - Davaris, PS
JO - Journal of Cancer Research and Clinical Oncology
PY - 2002
VL - 128
TODO - 2
SP - 114-118
PB - Springer-Verlag
SN - 0171-5216, 1432-1335
TODO - 10.1007/s00432-001-0310-5
TODO - colon cancer; P-glycoprotein; MRP; LRP; topoisomerase II alpha
TODO - Purpose: 5-Fluorouracil failure and drug resistance. which often occurs
during chemotherapy. is still a great obstacle to the success of human
colon cancer treatment. Thus. the comparative study of markers of drug
resistance in cancer cells before and after chemotherapy may be
extremely helpful in the selection of the appropriate chemotherapeutic
drug in colon cancer patients who fail adjuvant treatment with
5-fluorouracil. In the present study we examined the differential
expression of three multidrug resistance-related proteins (i.e.,
P-glycoprotein, MRP, and LRP) and of topoisomerase IIalpha in a series
of 20 primary colon carcinomas and their recurrences. Methods: All
markers were determined at tissue level by three-step
immunohistochemistry using appropriate monoclonal antibodies. and the
markers’ immunopositivity was quantified by image analysis. In addition.
Feulgen stain was used for the assessment of nuclear DNA content of
malignant cells at their primary location. Results: Some degree of
aneuploidy was detected in all primary carcinomas. The immunoexpression
of the three multidrug resistance-related proteins did not change
significantly, either qualitatively (positivity vs negativity) or
quantitatively, after chemotherapy. On the contrary, the percentages of
topoisomerase IIalpha-positive malignant cells were significantly
increased in the tumour recurrences by comparison to their primary
locations (P = 0.011). Conclusions: According to our results. increased
topoisomerase IIalpha immunohistochemical expression appears to be part
of the malignant cells’ phenotype in recurrent colon cancers.
Therapeutic options after failure of 5-fluorouracil-based treatment
could therefore include appropriate topoisomerase IIalpha-targeted
drugs.
ER -