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Expression dynamics of CXCL 12 and CXCR 4 during the progression of mycosis fungoides
Author(s) -
Daggett R.N.,
Kurata M.,
Abe S.,
Onishi I.,
Miura K.,
Sawada Y.,
Tanizawa T.,
Kitagawa M.
Publication year - 2014
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13054
Subject(s) - mycosis fungoides , cxcr4 , stage (stratigraphy) , pathology , chemokine , immunohistochemistry , real time polymerase chain reaction , carcinogenesis , biology , cancer , medicine , cancer research , receptor , lymphoma , gene , paleontology , biochemistry
Summary Background Mycosis fungoides ( MF ) classically presents from patch stage to plaque stage over a number of years and finally progresses to tumour stage with nodal or visceral involvement. The mechanism of progression remains incompletely elucidated. Chemokines and their receptors are known to be involved in disease mechanisms, with CXCL 12 and CXCR 4 playing a critical role in carcinogenesis, invasion and cancer cell migration in various carcinomas. Objectives To investigate the expression of CXCL 12 and CXCR 4 in different cutaneous stages of MF . Methods Formalin‐fixed, paraffin‐embedded skin samples from 40 patients with MF (21 patch stage, 10 plaque stage, nine tumour stage) and 30 non‐neoplastic control skin samples were analysed. CXCL 12 and CXCR 4 were assessed by quantitative reverse‐transcription polymerase chain reaction and immunohistochemical staining. Results The expression level of mRNA for CXCL12 in plaque‐stage MF was significantly higher than in control skin ( P = 0·0035), or patch‐stage ( P = 0·0108) or tumour‐stage disease ( P = 0·0089). The CXCR4 mRNA expression level in plaque‐stage disease was significantly higher than in control skin ( P = 0·0090) or patch‐stage disease ( P = 0·0387). CXCL12‐ and CXCR4‐positive cell rates in patch‐stage and plaque‐stage MF were significantly higher than those in control skin ( P < 0·0001). CXCL12‐ and CXCR4‐positve cell rates in tumour‐stage MF were significantly lower than those in patch‐ and plaque‐stage disease ( P = 0·0274 and P = 0·0492, respectively). Conclusions Our data suggest that neoplastic T cells in MF are exposed to the microenvironment, given the abundance of CXCL 12 during its progression, and also that neoplastic T cells express CXCR 4, especially in the pretumour stage. We reveal that the CXCL 12– CXCR 4 axis plays a critical role in MF progression.