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Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer
Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, R8 03, Stockholm, Sweden;Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus.
Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, R8 03, Stockholm, Sweden.
City Clin Pathologoanat Bur, Minsk, Byelarus.
Oslo Univ Hosp, Dept Oncol, Oslo, Norway;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway.
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2018 (English)In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 472, no 3, p. 395-405Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
SPRINGER , 2018. Vol. 472, no 3, p. 395-405
Keywords [en]
Colorectal cancer, Cell adhesion, Claudin-2, Cancer-associated fibroblasts
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-352989DOI: 10.1007/s00428-017-2263-3ISI: 000429350100009PubMedID: 29134439OAI: oai:DiVA.org:uu-352989DiVA, id: diva2:1233405
Funder
The Cancer Research Funds of RadiumhemmetSwedish Research CouncilSwedish Cancer SocietySwedish InstituteAvailable from: 2018-07-17 Created: 2018-07-17 Last updated: 2018-07-17Bibliographically approved

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