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Post a Comment Prognostic markers of recurrence in adrenocortical carcinoma patients after surgery
- Authors: Kalugina V.V.1, Vorokhobina N.V.1, Velikanova L.I.1, Shafigullina Z.R.1, Malevanaya E.V.1, Strelnikova E.G.1, Bokhyan V.Y.2, Britvin T.A.3, Kushlinskii N.E.2
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Affiliations:
- North-Western State Medical University named after I.I. Mechnikov
- N.N. Blokhin National Medical Research Center of Oncology
- Moscow Regional Research and Clinical Institute (MONIKI)
- Issue: Vol 15, No 2 (2023)
- Pages: 57-67
- Section: Original research
- URL: https://journals.rcsi.science/vszgmu/article/view/131105
- DOI: https://doi.org/10.17816/mechnikov233493
- ID: 131105
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Abstract
BACKGROUND: Adrenocortical carcinoma is a rare and aggressive disease. Tumor recurrence prevention is vital for increasing patients’ survival rate. Therefore, the identification of prognostic markers is of particular importance.
AIM: To evaluate clinical, laboratory and chromatographic criteria for adrenocortical carcinoma recurrence using gas chromatography-mass spectrometry to optimize patient’s follow-up.
MATERIALS AND METHODS: 40 patients [10 (25%) men and 30 (75%) women] with histologically confirmed adrenocortical carcinoma (according to the European Network for the Study of Adrenal Tumors stage I — 3, II — 29, III — 8 patients at presentation) have been recruited. Measurement of 24-hour urinary steroid metabolite excretion has been carried out by gas chromatography-mass spectrometry (GCMS-ТQ8050, Shimadzu) in preoperative period. The survival distribution has been assessed according to the Kaplan–Meier method. Cox proportional hazards regression methods have been used to determine predictive factors on recurrence-free survival.
RESULTS: The patients with early stages of disease (I–II versus III) had a significantly longer recurrence-free survival, overt hypercortisolism was associated with significantly shorter recurrence-free survival. A significant correlation between pregnenediol urinary excretion and tumor diameter, stage has been found. Increased urinary excretion of tetrahydro-11-deoxycortisol, pregnenediol was associated with a decreased recurrence-free survival in the patients with overt hypercortisolism. Increased urinary excretion of 16-OH-dehydroepiandrosterone was a marker of a shorter recurrence-free survival in the patients without Cushing syndrome. Increased urinary excretion of pregnenediol, pregnenetriol, 16-oxo-androstenediol in all the adrenocortical carcinoma patients was associated with a recurrence risk. In the multivariate analysis pregnenediol urinary excretion, stage and overt cortisol excess were significantly and independently associated with a shorter recurrence-free survival.
CONCLUSIONS: Adrenocortical carcinoma recurrence prognostic markers have been found by gas chromatography-mass spectrometry. The application of these findings may improve patient-centered outcomes.
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##article.viewOnOriginalSite##About the authors
Valentina V. Kalugina
North-Western State Medical University named after I.I. Mechnikov
Email: kaluginavav@gmail.com
ORCID iD: 0000-0002-2812-6911
SPIN-code: 3996-7284
MD
Russian Federation, Saint PetersburgNatalia V. Vorokhobina
North-Western State Medical University named after I.I. Mechnikov
Email: natvorokh@mail.ru
ORCID iD: 0000-0002-9574-105X
SPIN-code: 4062-6409
MD, Dr. Sci. (Med.), Professor
Russian Federation, Saint PetersburgLudmila I. Velikanova
North-Western State Medical University named after I.I. Mechnikov
Email: velikanova46@gmail.com
ORCID iD: 0000-0002-9352-4035
SPIN-code: 5586-4851
Scopus Author ID: 6701531680
Dr. Sci. (Biol.), Professor
Russian Federation, Saint PetersburgZulfiya R. Shafigullina
North-Western State Medical University named after I.I. Mechnikov
Email: zula183@mail.ru
ORCID iD: 0000-0001-8292-8504
SPIN-code: 7569-3823
MD, Cand. Sci. (Med.)
Russian Federation, Saint PetersburgEkaterina V. Malevanaya
North-Western State Medical University named after I.I. Mechnikov
Author for correspondence.
Email: e.malevanaia@gmail.com
ORCID iD: 0000-0003-0880-0814
SPIN-code: 8814-0716
Scopus Author ID: 55657420600
Cand. Sci. (Chem.)
Russian Federation, 41 Kirochnaya St., Saint Petersburg, 191015Elena G. Strelnikova
North-Western State Medical University named after I.I. Mechnikov
Email: lstrelnikova@inbox.ru
ORCID iD: 0000-0002-1208-8092
SPIN-code: 6631-6962
Scopus Author ID: 57190013028
Cand. Sci. (Chem.)
Russian Federation, Saint PetersburgVagan Yu. Bokhyan
N.N. Blokhin National Medical Research Center of Oncology
Email: v_bokhyan@kand.ru
ORCID iD: 0000-0002-9066-5190
SPIN-code: 1040-0138
Scopus Author ID: 6507344683
MD, Dr. Sci. (Med.)
Russian Federation, MoscowTimur A. Britvin
Moscow Regional Research and Clinical Institute (MONIKI)
Email: t.britvin@gmail.com
ORCID iD: 0000-0001-6160-1342
SPIN-code: 1207-2935
Scopus Author ID: 6506344903
MD, Dr. Sci. (Med.), Professor
Russian Federation, MoscowNikolay E. Kushlinskii
N.N. Blokhin National Medical Research Center of Oncology
Email: kne3108@gmail.com
ORCID iD: 0000-0002-3898-4127
SPIN-code: 6225-1487
Scopus Author ID: 7005430266
MD, Dr. Sci. (Med.), Professor, Academician of RAS
Russian Federation, MoscowReferences
- Melnichenko GA, Stilidi IS, Alekseev BY, et al. Federal clinical practice guidelines on the diagnostics and treatment of adrenocortical cancer. Problems of Endocrinology. 2014;60(2):51–67. (In Russ.) doi: 10.14341/probl201460251-67
- Chandrasekar T, Goldberg H, Klaassen Z, et al. The who, when, and why of primary adrenal malignancies: Insights into the epidemiology of a rare clinical entity. Cancer. 2019;125(7):1050–1059. doi: 10.14341/probl201460251-67
- Crona J, Beuschlein F. Adrenocortical carcinoma – towards genomics guided clinical care. Nat Rev Endocrinol. 2019;15(9):548–560. doi: 10.1038/s41574-019-0221-7
- Fassnacht M, Assie G, Baudin E, et al. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(11):1476–1490. doi: 10.1016/j.annonc.2020.08.2099
- Bilimoria KY, Shen WT, Elaraj D, et al. Adrenocortical carcinoma in the United States: Treatment utilization and prognostic factors. Cancer. 2008;113(11):3130–3136. doi: 10.1002/cncr.23886
- Terzolo M, Fassnacht M. Endocrine tumours: Our experience with the management of patients with non-metastatic adrenocortical carcinoma. Eur J Endocrinol. 2022;187(3):R27–R40. doi: 10.1530/EJE-22-0260
- Beuschlein F, Weigel J, Saeger W, et al. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection. J Clin Endocrinol Metab. 2015;100(3):841–849. doi: 10.1210/jc.2014-3182
- Papathomas TG, Pucci E, Giordano TJ, et al. An international Ki67 reproducibility study in adrenal cortical carcinoma. Am J Surg Pathol. 2016;40(4):569–576. doi: 10.1097/PAS.0000000000000574
- Berruti A, Fassnacht M, Haak H, et al. Prognostic role of overt hypercortisolism in completely operated patients with adrenocortical cancer. Eur Urol. 2014;65(4):832–838. doi: 10.1016/j.eururo.2013.11.006
- Arlt W, Biehl M, Taylor AE, et al. Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. J Clin Endocrinol Metab. 2011;96(12);3775–3784. doi: 10.1210/jc.2011-1565
- Velikanova LI, Shafigullina ZR, Lisitsin AA, et al. Different types of urinary steroid profiling obtained by high-performance liquid chromatography and gas chromatography-mass spectrometry in patients with adrenocortical carcinoma. Horm Cancer. 2016;7(5–6):327–335. doi: 10.1007/s12672-016-0267-0
- Chortis V, Bancos I, Nijman T, et al. Urine steroid metabolomics as a novel tool for detection of recurrent adrenocortical carcinoma. J Clin Endocrinol Metab. 2020;105(3):e307–e318. doi: 10.1210/clinem/dgz141
- Weiss LM, Medeiros LJ, Vickerly AL. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol. 1989;13(3):202–205. doi: 10.1097/00000478-198903000-00004
- Velikanova LI, Strel’nikova EG, Obedkova EV, et al. Generation of urinary steroid profiles in patients with adrenal incidentaloma using gas chromatography–mass spectrometry. J Anal Chem. 2016;71(7):748–754. doi: 10.1134/S1061934816070169
- Ronchi CL, Sbiera S, Leich E, et al. Low SGK1 expression in human adrenocortical tumors is associated with ACTH-independent glucocorticoid secretion and poor prognosis. J Clin Endocrinol Metab. 2012;97(12):E2251–E2260. doi: 10.1210/jc.2012-2669
- Calabrese A, Basile V, Puglisi S, et al. Adjuvant mitotane therapy is beneficial in non-metastatic adrenocortical carcinoma at high risk of recurrence. Eur J Endocrinol. 2019;180(6):387–396. doi: 10.1530/EJE-18-0923
- Kerkhofs TM, Kerstens MN, Kema IP, et al. Diagnostic value of urinary steroid profiling in the evaluation of adrenal tumors. Horm Cancer. 2015;6(4):168–175. doi: 10.1007/s12672-015-0224-3
- Elhassan YS, Altieri B, Berhane S, et al. S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study. Eur J Endocrinol. 2022;186(1):25–36. doi: 10.1530/EJE-21-0510
- Zheng S, Cherniack AD, Dewal N, et al. Comprehensive pan-genomic characterization of adrenocortical carcinoma. Cancer Cell. 2016;29(5):723–736. doi: 10.1016/j.ccell.2016.04.002
- Assié G, Letouzé E, Fassnacht M, et al. Integrated genomic characterization of adrenocortical carcinoma. Nat Genet. 2014;46(6);607–612. doi: 10.1038/ng.2953
- Assié G, Jouinot A, Fassnacht M, et al. Value of molecular classification for prognostic assessment of adrenocortical carcinoma. JAMA Oncol. 2019;5(10):1440–1447. doi: 10.1001/jamaoncol.2019.1558
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