Journal
VIRCHOWS ARCHIV
Volume 472, Issue 3, Pages 395-405Publisher
SPRINGER
DOI: 10.1007/s00428-017-2263-3
Keywords
Colorectal cancer; Cell adhesion; Claudin-2; Cancer-associated fibroblasts
Categories
Funding
- Swedish Cancer Society (Cancerfonden)
- Radiumhemmets forskningsfonder
- STARGET Linne-grant from Swedish Research Council
- Svenska Institutet
- Swedish Cancer Society
- Merck KGaA (Darmstadt, Germany)
- Sanofi (Oslo, Norway)
- Norwegian Cancer Society
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Claudin-2 is a trans-membrane protein-component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types. Claudin-2 expression was also analyzed by immunofluorescence in primary cultures of human CRC cancer-associated fibroblasts (CAFs). Initial analyses identified previously unrecognized expression patterns of claudin-2 in CAFs of human CRC. Claudin-2 expression in CAFs of the invasive margin was associated with shorter progression-free survival. Subgroup analyses demonstrated that the survival associations occurred among cases that received 5-FU+oxaliplatin combination treatment, but not in patients receiving 5-FU +/- irinotecan. The finding was validated by analyses of the independent cohort. In summary, previously unreported stromal expression of claudin-2 in CAFs of human CRC was detected together with significant association between high claudin-2 expression in CAFs and shorter survival in 5-FU+oxaliplatin-treated mCRC patients.
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