Determination of Tumor-infiltrating CD8+ Lymphocytes in Human Ovarian Cancer

Tumor-infiltrating immune cells and their prognostic value have been analyzed in various malignancies. Although tissue microarray (TMA) has been used in some of these studies, it is still questionable whether this technique can represent the results of infiltrating CD8(+) cells obtained from whole-tissue sections (WTS). The aim of this study was to assess and compare the density of tumor-infiltrating CD8(+) cells in ovarian cancer using TMA and WTS. CD8(+) lymphocytes were immunohistochemically stained on WTS and TMA cores from 37 ovarian cancer patients and quantified using the image analysis software HistoQuest. Four different areas were selected on the WTS, namely (i) tumor; (ii) stroma; (iii) mixed; and (iv) dense, whereby dense represented areas of most abundant CD8(+) cells. On the TMA, (i) the whole TMA cores and (ii) areas containing only epithelial tumor tissue were analyzed. The Pearson correlation and principal component analysis was used to estimate the correlation of results from different techniques. CD8(+) lymphocytes showed highly correlated measurements between tumor, mixed, and dense areas. Moderate correlations were found between each of these 3 measurements and stroma. CD8(+) cell counts from WTS showed moderate correlation with TMA cell counts. Consistently, principal component analysis showed 3 clusters (i) tumor, dense, mixed; (ii) stroma; and (iii) TMA areas. Taken together, when the prognostic impact of tumor-infiltrating CD8(+) cells in ovarian cancer is investigated with TMA technique, a moderate correlation with WTS results has to be considered.