期刊
INTERNATIONAL JOURNAL OF CANCER
卷 127, 期 5, 页码 1028-1037出版社
WILEY
DOI: 10.1002/ijc.25114
关键词
liver metastases; colorectal cancer; genetic heterogeneity; primary culture
类别
资金
- Association pour la Recherche en Oncologie Digestive (AROLD) association
A goal of oncology is to predict chemosensitivity of tumors. This approach assumes that in a patient all tumor deposits are homogeneous. We have tested the heterogeneity between several samples of the same liver metastasis (LM; intrametastatic heterogeneity) or between multiple LM (intermetastatic heterogeneity) from colorectal cancer in a single patient. In 16 untreated patients, several fragments of LM and nontumorous liver were collected. Heterogeneity to anticancer drug treatment was assessed in vitro on primary tissue cultures on poly-HEMA-coated surface with or without the topoisomerase-I inhibitor metabolite SN-38. Heterogeneity of response to SN-38 was observed in 55% of cases from one fragment to another in the same LM and in 64% of cases from one LM to another in the same patient. Allelic losses were characterized on 5q, 8p, 17p, 18q, 22q using 29 microsatellites markers. Seven patients (58%) had a perfect homogeneity for allelic losses in their LM whereas 3 (21%) had intrametastatic and 2 (18%) had intermetastatic heterogeneity. The analysis of gene expression was carried out by real time RT-PCR quantification using specific probes for TS, TOPO1, ERCC1, and CES2. Level expression of genes tested appeared heterogeneous with average variations of 57(+/- 23)%, 52(+/- 18)%, 53(+/- 18)%, 56(+/- 16)% for TS, TOPO1, ERCC1, and CES2 respectively for intermetastatic variability and 47(+/- 26)%, 36(+/- 14)%, 38(+/- 19)%, and 56(+/- 29)%, respectively for intrametastatic variability. Our results demonstrate intermetastatic and intrametastatic heterogeneity suggesting that pretherapeutic analysis of a single tumor biopsy is likely to lead to a misinterpretation of sensitivity to anticancer treatment.
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