Clinical Impact of Natural Killer Group 2D Receptor Expression and That of Its Ligand in Ovarian Carcinomas: A Retrospective Study
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Purpose: Natural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptorexpressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current studyaimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it alsoexamined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathologicalparameters, and prognosis. Materials and Methods: Formalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissuesamples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands(MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the associationbetween these results and clinical prognostic parameters was analyzed statistically. Results: ULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression ofULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression ofULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independentpredictor of better survival. Conclusion: High expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novelprognostic indicator in this subset of carcinomas.
Abstract
Purpose: Natural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptorexpressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current studyaimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it alsoexamined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathologicalparameters, and prognosis. Materials and Methods: Formalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissuesamples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands(MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the associationbetween these results and clinical prognostic parameters was analyzed statistically. Results: ULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression ofULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression ofULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independentpredictor of better survival. Conclusion: High expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novelprognostic indicator in this subset of carcinomas.
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