Relationship of tumor-associated macrophage population detected by CD68 PG-m1, cd68 kp1 and CD163 with latent EBV infection and prognosis in classical hodgkin's lymphoma

AİM: Our aim is to evaluate the quantity of tissue associated macrophages (TAM), detected by CD68 PG-M1, CD68 KP1 and CD163 positivity and its correlation between latent EBV infection in neoplastic cells, and to reveal the possible association of overall and progression free survival in cases of Hodgkin's lymphoma of classical type (cHL); to see also whether there is an association with prognostic indices such as International Prognostic Score (IPS) and European Organization for Research and Treatment of Cancer (EORTC) and clinicopathological parameters. MATERIALS AND METHODS: 46 cases of Hodgkin's lymphoma classical type were selected for evaluation. Staining for CD68 (PG-M1 and KP1 clones) and CD163 immunohistochemistry were evaluated, cut-off values were defined according to median values of staining intensity and ratio. The significance of values lower than median values were also reviewed to determine their statistical importance. Additionally, all cases were evaluated using chromogen in situ hybridization (CISH) method with EBER (Epstein-Barr virus encoded RNA) probes for presence of possible EBV infection. RESULTS: We found high expression levels of CD68 PG-M1 and high IPS were associated with shortened overall survival (p= 0,047 and 0,013, respectively). Association with parameters such as advanced stage disease, presence of extralymphatic involvement, high erythrocyte sedimentation rate (ESR>50) and being in the poor risk group for EORTC were also found statistically significant for shortened overall survival (p=0,090, p=0,067, p=0,073 and p=0,076 respectively). Cases with 2 or less nodal region involvement have been observed to have longer progression-free survival period, also there was statistically borderline significant association with presence of EBV infection (p=0,043 and p=0,062 respectively). Presence of extralymphatic involvement and high ESR (>50) were found to shorten progression-free survival as well as overall survival, again in a borderline manner (p=0,051 and p=0,090 respectively). High expression levels with immunohistochemical markers (CD68 PG-M1, CD68 KP1 and CD163) were found to show association with presence of clinical parameters such as, presence of B symptoms, spleen involvement, being in the poor risk group for EORTC and presence of EBV infection. High CD163 expression levels were associated with high IPS, high ESR and older age (p=0,037, p=0,017 and p=0,008 respectively). Higher staining intensity with CD68 PG-M1 were associated with high ESR, male sex and neoplastic cell count being intermediate/high (p=0,038, p=0,023, p=0,012, respectively). Higher staining intensity with CD68 KP1 were associated with higher IPS (p=0,038). In multivariate analysis, each three markers have also shown significant relevance with presence of EBV infection and B symptoms, while spleen involvement were found to have correlation with CD163 and CD68 PG-M1. CONCLUSIONS: Our findings suggest that increase of CD68 PG-M1+ TAM with a cut-off point of 40% is associated with shortened overall survival, while the remaining markers were observed to have no such significant association with overall or progression-free survival. Presence of EBV infection and clinical parameters mentioned above and used for determining risk groups, showed significant association with each marker. These findings indicate that highlighting TAM rate via macrophage markers in cases of cHL could be helpful determining prognostic risk groups and should be mentioned in pathology reports. In order to obtain more accurate results, this subject is needed to be evaluated in other studies including larger series with much more longer follow-up periods.