AN IMMUNOHISTOCHEMICAL EVALUATION OF TUMOR ASSOCIATED MACROPHAGES (M1 & M2) IN CARCINOMA PROSTATE- AN INSTITUTIONAL STUDY

Abstract

BACKGROUND: Prostate cancer is primarily a disease of the older men with more than three quarter of the cases occurring above 65 years of age. Studies showed that prostate carcinoma is the second most commonly diagnosed carcinoma in men worldwide and the fifth most common cancer overall. Tumor associated macrophages(TAM) are main component of inflammation along with leukocytes, vascular endothelial cells and fibroblasts together form a tumor microenvironment, with immune cells representing its vital component. Many studies suggested that TAMs cumulation in tumors correlates with a poor prognosis. In prostate cancer, TAMs can enhance cancer cell invasion by stimulating tumor angiogenesis, degrading the extracellular matrix, and also suppresses the anti-tumor functions of cytotoxic T cells resulting in poor prognosis. Therefore, TAMs are an alluring target for therapeutic intervention by targeting their various function. Hence the study is undertaken. On H and E section, it is difficult to differentiate M1 and M2 phenotypes. Hence Immunostaining is used to identify M1 and M2 sub population of macrophages. CD68 is been taken as a marker for M1 macrophage and CD163 is been taken as a marker for M2 macrophage. Only few studies determining expression of CD68 and CD163 have been done on prostate Cancers and published in Indian Literature so far. Hence the study is undertaken to determine the expression of CD68 and CD163 in prostate Carcinomas. xiv AIMS AND OBJECTIVES: • To determine the expression of M1 (CD68)and M2 (CD163) in prostate cancer. • To find association between M1 , M2 Macrophage with Gleason’s score & Stage of the disease in prostate carcinoma. MATERIALS AND METHODS: This is a retrospective observational study. All Transurethral resected Prostatic(TURP) Chips positive for prostate carcinoma, received in the Department of Pathology Sri Devaraj Urs Medical College, Tamaka, and Kolar . from December 2019 to October 2021 and also the paraffin blocks taken from all cases of Prostate cancer retrieved from Archives of Department of Pathology from the year January 2015 to November 2019 were included in the study. All Transurethral resected prostatic(TURP) Chips positive for carcinoma prostate confirmed by histopathological examination was included in the study. Data regarding the clinical details (age, Stage of the disease) was collected. H and E slides was reviewed for Histopathological types and Gleason’s score of the tumor. Radiologic findings (USG,MRI or CT Findings) with respect to stage of disease, size of lesion, was noted. The CD 68 and CD 163 immuno stained slides were examined under low power ( 10X) and was looked for areas with maximum expression of CD 68 and CD 163 by two observers and were called as” Hot spots” . These hotspots were then viewed under higher magnification (40X) and CD 68 and CD 163 positive cells were counted and scoring was done on number of macrophages expressed by IHC. xv RESULTS: A total of 62 cases were studied and majority of the patients were in-between age of 61-70 years. Highest number of cases were in Gleason’s score 8,9, 10 (62%), PSA levels 20-80ng/ml (64%), Tumor Size 3-6 cm (51.6%), T3 stage (40.3 %) , N1 lymph node stage (70.9%). M1 stage of (31%). CD 68 and Cd163 expression was analyzed with Gleason’s score, TNM stage and PSA levels. CD68 score 3 was associated with low nodal and distant metastasis 6.8%) and 6.2% respectively. CD163 Score 3 was associated with high metastasis to lymph node and distant metastasis of 86.3% and 25% respectively. On further analysis, statistically significant association between the CD 163 expression and Gleason’s score, PSA levels, nodal and distant metastasis was found. CONCLUSION: CD 68 expression was associated with better prognosis with less nodal and distant metastasis and Cd163 expression has poor outcome with increased chances of nodal and distant metastasis. Further exploration of TAM mechanisms and immune checkpoints in the prostate tumor microenvironment can provide new light and idea for the treatment of prostate carcinoma.