Intratumoral neutrophils, plasmacytoid dendritic cells, and pSTAT3 in AJCC stage I/II melanoma prognosis.

Abstract

8553 Background: Interactions between tumor cells and host immune cells play a key role in carcinogenesis. Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer and is believed to be an important mediator of tumor-induced immuno-suppression. We studied the prognostic role of neutrophil and dendritic cell infiltration in primary melanomas and their association with activated STAT3 (pSTAT3) in primary melanoma cells. Methods: Formalin-fixated, paraffin-embedded primary melanomas from 187 stage I/II melanoma patients treated with surgical resection in 1997 to 2000 were included. Infiltrating neutrophils (CD66b+), dendritic cells (CD123+ and DC-LAMP+), and melanoma cell expression of pSTAT3 were studied by immunohistochemistry and evaluated as present or absent. Study endpoints were: Relapse-free survival, melanoma-specific and overall survival. Results: After a median observation time of 9.5 years (range 7.0-11.4 years), 39 deaths (21%) were observed, of which 31 (17%) were melanoma-specific. In a multivariate Cox proportional hazards model including ulceration and melanoma thickness, neutrophil- and CD123+ dendritic cell infiltration were independently associated with poor prognosis (CD66b+: HR=3.14 95% CI, 1.31-7.54 P=0.010; CD123+: HR=2.56 95% CI, 1.16-5.64 P=0.020). There was a strong association between melanoma cell pSTAT3 expression and neutrophil/CD123+ dendritic cell infiltration. pSTAT3 expression and DC-LAMP infiltration were not independently associated with poor prognosis. Conclusions: Neutrophil infiltration and CD123+ dendritic cell infiltration in primary melanoma are independently associated with poor prognosis. Melanoma cell expression of pSTAT3 is strongly associated with neutrophil and CD123+ dendritic cell infiltration.