Abstract
Adrenocortical tumors (ACT) are common adrenal tumors. The majority of ACTs are non-functioning and benign, while adrenocortical carcinomas (ACC) are rare, usually very aggressive and often metastasized when first diagnosed. Our aim was to assess whether blood and lymph vessel density within ACTs correlate with the malignancy character or tumor functionality. For that, the microvascular distribution was evaluated by immunohistochemistry staining with D2–40 antibody, for lymph vessels and CD-31 antibody, for blood vessels, in ACCs (n = 15), adenomas with Cushing syndrome (n = 9) and non-functioning adenomas (n = 10). The percentage of stained area was quantified by computerized morphometric analysis. D2–40 expression was significantly lower in ACC as compared to adenomas with Cushing syndrome (p < 0.01) and correlated positively with the expression of the steroidogenic acute regulatory protein (StAR) (R2 = 0.553, p < 0.001). CD31 expression was found to be significantly higher in ACC as compared to adenomas with Cushing syndrome (p < 0.05). Our results show that angiogenesis is increased in ACC, suggesting that this phenomenon may have an important role in ACT biological behavior, while lymph vascular density seems to be more closely related to the tumor functional status than malignancy.
References
Allolio B, Hahner S, Weismann D, Fassnacht M (2004) Management of adrenocortical carcinoma. Clin Endocrinol 60(3):273–287
Paduch R (2016) The role of lymphangiogenesis and angiogenesis in tumor metastasis. Cell Oncol (Dordr) 39(5):397–410. doi:10.1007/s13402-016-0281-9
Alitalo K, Tammela T, Petrova TV (2005) Lymphangiogenesis in development and human disease. Nature 438(7070):946–953. doi:10.1038/nature04480
Pusztaszeri MP, Seelentag W, Bosman FT (2006) Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem 54(4):385–395. doi:10.1369/jhc.4A6514.2005
Browning L, Bailey D, Parker A (2008) D2-40 is a sensitive and specific marker in differentiating primary adrenal cortical tumours from both metastatic clear cell renal cell carcinoma and phaeochromocytoma. J Clin Pathol 61(3):293–296. doi:10.1136/jcp.2007.049544
Bernini GP, Moretti A, Bonadio AG, Menicagli M, Viacava P, Naccarato AG, Iacconi P, Miccoli P, Salvetti A (2002) Angiogenesis in human normal and pathologic adrenal cortex. J Clin Endocrinol Metab 87(11):4961–4965. doi:10.1210/jc.2001-011799
Zhu Y, Xu Y, Chen D, Zhang C, Rui W, Zhao J, Zhu Q, Wu Y, Shen Z, Wang W, Ning G, Wang X (2014) Expression of STAT3 and IGF2 in adrenocortical carcinoma and its relationship with angiogenesis. Clin Transl Oncol 16(7):644–649. doi:10.1007/s12094-013-1130-1
Pereira SS, Morais T, Costa MM, Monteiro MP, Pignatelli D (2013) The emerging role of the molecular marker p27 in the differential diagnosis of adrenocortical tumors. Endocr Connect 2(3):137–145. doi:10.1530/EC-13-0025
Logie JJ, Ali S, Marshall KM, Heck MM, Walker BR, Hadoke PW (2010) Glucocorticoid-mediated inhibition of angiogenic changes in human endothelial cells is not caused by reductions in cell proliferation or migration. PLoS One 5(12):e14476. doi:10.1371/journal.pone.0014476
De Fraipont F, El Atifi M, Gicquel C, Bertagna X, Chambaz E, Feige J (2000) Expression of the angiogenesis markers vascular endothelial growth factor-a, Thrombospondin-1, and platelet-derived endothelial cell growth factor in human sporadic adrenocortical tumors: correlation with genotypic alterations 1. J Clin Endocrinol Metab 85(12):4734–4741
Moreira A, Pereira SS, Machado CL, Morais T, Costa M, Monteiro MP (2014) Obesity inhibits lymphangiogenesis in prostate tumors. Int J Clin Exp Pathol 7(1):348–352
Ozerdem U, Wojcik EM, Duan X, Ersahin C, Barkan GA (2013) Prognostic utility of quantitative image analysis of microvascular density in prostate cancer. Pathol Int 63(5):277–282. doi:10.1111/pin.12056
Pereira F, Pereira SS, Mesquita M, Morais T, Costa MM, Quelhas P, Lopes C, Monteiro MP, Leite V (2017) Lymph node metastases in papillary and medullary thyroid carcinoma are independent of Intratumoral lymphatic vessel density. European Thyroid Journal 6(2):57–64
Kyle LH, Meyer RJ, Canary JJ (1957) Mechanism of adrenal atrophy in Cushing’s syndrome due to adrenal tumor. N Engl J Med 257(2):57–61. doi:10.1056/NEJM195707112570203
Acknowledgements
The authors would like to acknowledge Prof. Eduardo Rocha, Célia Lopes and Fernanda Malhão for valuable technical support
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Grants
This study was supported by the Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/89308/2012 and SFRH/BPD/111741/2015). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT. Unit for Multidisciplinary Research in Biomedicine is also funded by FCT (UID/Multi/00215/2013).
Conflict of Interest
The authors declare that they have no conflict of interest.
Informed Consent
The participants provided written informed consent for adrenal tissue samples deposited at our institutional Tumor Bank to be used for future research.
Ethical Approval
The study was approved by the local Ethics Committee.
Rights and permissions
About this article
Cite this article
Pereira, S.S., Costa, M.M., Guerreiro, S.G. et al. Angiogenesis and Lymphangiogenesis in the Adrenocortical Tumors. Pathol. Oncol. Res. 24, 689–693 (2018). https://doi.org/10.1007/s12253-017-0259-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12253-017-0259-6