The Significance of Inflammatory Cell Infiltration in Cortisol-Producing Adrenocortical Adenomas (CPA): A Possible Insight into Its Involvement in Pathogenesis of CPA

Presentation Number: MON 389
Date of Presentation: April 3rd, 2017

Yuko Kitawaki*1, Yasuhiro Nakamura2, Fumie Kubota-Nakayama3, Yuto Yamazaki1, Shuko Hata2, Kazue Ise2, Ryo Morimoto4, Kumi Kikuchi4, Fumitoshi Satoh1 and Hironobu Sasano1
1Tohoku University Graduate School of Medicine, Sendai, Japan, 2Tohoku Medical and Pharmaceutical University, Sendai, Japan, 3Tohoku Rosai Hospital, 4Tohoku University Hospital, Sendai, Japan

Abstract

Backgrounds: Cortisol-producing adrenocortical adenoma (CPA) and aldosterone-producing adenoma (APA) are two major functional adrenocortical adenomas with different histological features. Among these, intratumoral infiltration of inflammatory cells is frequently detected in CPA but extremely rare in APA but its mechanisms have been unexplored. Therefore, we examined the possible mechanisms of this inflammatory cell infiltration in CPA in this study.

Objectives: We aimed to evaluate the details of intratumoral inflammatory cell infiltration in CPA and APA and to analyze the expression profiles of cytokines and chemokines in these tumors in order to explore the mechanisms of recruiting these inflammatory cells in the tumor tissue.

Methods: Immunohistochemical analysis was performed in eight CPA cases containing abundant intratumoral inflammatory cells. In addition, expression profiles of 84 genes reported to be involved in the recruitment of the inflammatory cells were evaluated by employing PCR array analysis in three each of CPA and APA cases. Results of the array were also validated by quantitative RT-PCR in these six cases and also immunohistochemical analyses in 21 CPAs and 13 APAs for further confirmation.

Results: Results of immunohistochemical analysis did reveal that intratumoral inflammatory cells in CPA were all composed of B and T lymphocytes and macrophages but T lymphocytes were predominant. PCR array analysis demonstrated significantly higher expressions of CXCL1, CXCL2 and CXCL5 (C-X-C Motif Chemokine Ligand), which all play pivotal roles as chemoattractant for neutrophils or in the proliferation and progression of certain tumors, in CPA cases compared to APA cases [p=0.0052, p=0.0215, p=0.0291, respectively]. The subsequent quantitative RT-PCR and immunohistochemical evaluations also revealed that the expressions of CXCL1/2 mRNA and protein were significantly higher in CPA than APA cases [p=0.0066, p=0.032, p<.0001, p<.0001, respectively]. In addition, CXLC1/2 mRNA and protein were significantly correlated with the degree of intratumoral inflammatory cell infiltration [CXCL1 mRNA: ρ=0.523(p=0.0061), CXCL2 mRNA: ρ=0.4758(p=0.0140), CXCL1 protein: ρ=0.7420(p<.0001), CXCL2 protein: ρ=0.6795(p<.0001), respectively].

Conclusions: Results of our present study firstly demonstrated that both CXCL1 and CXCL2 were abundantly expressed in tumor cells of CPA cases and possibly recruited intratumoral infiltration of inflammatory cells, especially T lymphocytes.

 

Nothing to Disclose: YK, YN, FK, YY, SH, KI, RM, KK, FS, HS