Prognostic impact of CD31-positive microvessel density in follicular lymphoma patients treated with immunochemotherapy.
BACKGROUND
Tumour-infiltrating mast cells (MCs) can remodel tumour microenvironment and growth by suppressing immune responses and potentiating angiogenesis. Furthermore, accumulation of MCs in follicular lymphoma (FL) correlates with unfavourable prognosis after immunochemotherapy. Here we investigated whether tumour vascularity is associated with MC content and outcome in FL patients treated with immunochemotherapy.


METHODS
Microvessel density (MVD) and MC content were determined immunohistochemically from pretreatment samples of 95 FL patients using CD31, CD34 and mast cell tryptase antibodies. Gene expression data from a separate set of 24 FL patients were analysed for comparison. All patients were treated with the combination of rituximab (R) and cyclophoshamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy.


RESULTS
Increased CD31+ MVD correlated positively with the number of tumour infiltrating MCs and CD34+ vessels, and negatively with the outcome. Overall survival and progression-free survival were significantly better among patients with low CD31+ MVDs. In multivariate analyses, CD31+ MVD had prognostic value independently of Follicular Lymphoma Prognostic Index but not of MC content. Consistent with the immunohistochemical data, high CD31/PECAM1 mRNA levels were associated with adverse outcome. Conversely, a positive prognostic impact of VEGF mRNA expression on the outcome was found.


CONCLUSIONS
Vascularity is associated with MC content and outcome in R-CHOP-treated FL patients.
Taskinen
Minna
M
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Jantunen
Esa
E
Kosma
Veli-Matti
VM
Bono
Petri
P
Karjalainen-Lindsberg
Marja-Liisa
ML
Leppä
Sirpa
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008224:Lymphoma, Follicular / Q000473:pathology / Q000628:therapy*; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone