Prognostic markers of recurrence in adrenocortical carcinoma patients after surgery
Valentina V. Kalugina , Natalia V. Vorokhobina , Ludmila I. Velikanova , Zulfiya R. Shafigullina , Ekaterina V. Malevanaya , Elena G. Strelnikova , Vagan Yu. Bokhyan , Timur A. Britvin , Nikolay E. Kushlinskii
HERALD of North-Western State Medical University named after I.I. Mechnikov ›› 2023, Vol. 15 ›› Issue (2) : 57 -67.
Prognostic markers of recurrence in adrenocortical carcinoma patients after surgery
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.
adrenocortical carcinoma / recurrence / prognostic markers / gas chromatography-mass spectrometry
| [1] |
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 |
| [2] |
Мельниченко Г.А., Стилиди И.С., Алексеев Б.Я. и др. Федеральные клинические рекомендации по диагностике и лечению адренокортикального рака // Проблемы Эндокринологии. 2014. Т. 60, № 2. С. 51–67. DOI: 10.14341/probl201460251-67 |
| [3] |
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 |
| [4] |
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. Vol. 125, No. 7. P. 1050–1059. DOI: 10.1002/cncr.31916 |
| [5] |
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 |
| [6] |
Crona J., Beuschlein F. Adrenocortical carcinoma – towards genomics guided clinical care // Nat. Rev. Endocrinol. 2019. Vol. 15, No. 9. P. 548–560. DOI: 10.1038/s41574-019-0221-7 |
| [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 |
| [8] |
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. Vol. 31, No. 11. P. 1476–1490. DOI: 10.1016/J.ANNONC.2020.08.2099 |
| [9] |
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 |
| [10] |
Bilimoria K.Y., Shen W.T., Elaraj D. et al. Adrenocortical carcinoma in the United States: Treatment utilization and prognostic factors // Cancer. 2008. Vol. 113, No. 11. P. 3130–3136. DOI: 10.1002/cncr.23886 |
| [11] |
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 |
| [12] |
Terzolo M., Fassnacht M. Endocrine tumours: Our experience with the management of patients with non-metastatic adrenocortical carcinoma // Eur. J. Endocrinol. 2022. Vol. 187, No. 3. P. R27–R40. DOI: 10.1530/EJE-22-0260 |
| [13] |
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 |
| [14] |
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. Vol. 100, No. 3. P. 841–849. DOI: 10.1210/jc.2014-3182 |
| [15] |
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 |
| [16] |
Papathomas T.G., Pucci E., Giordano T.J. et al. An international Ki67 reproducibility study in adrenal cortical carcinoma // Am. J. Surg. Pathol. 2016. Vol. 40, No. 4. P. 569–576. DOI: 10.1097/PAS.0000000000000574 |
| [17] |
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 |
| [18] |
Berruti A., Fassnacht M., Haak H. et al. Prognostic role of overt hypercortisolism in completely operated patients with adrenocortical cancer // Eur. Urol. 2014. Vol. 65, No. 4. P. 832–838. DOI: 10.1016/j.eururo.2013.11.006 |
| [19] |
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 |
| [20] |
Arlt W., Biehl M., Taylor A.E. et al. Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors // J. Clin. Endocrinol. Metab. 2011. Vol. 96, No. 12. P. 3775–3784. DOI: 10.1210/jc.2011-1565 |
| [21] |
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 |
| [22] |
Velikanova L.I., Shafigullina Z.R., Lisitsin A.A. 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. Vol. 7, No. 5–6. P. 327–335. DOI: 10.1007/s12672-016-0267-0 |
| [23] |
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 |
| [24] |
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. Vol. 105, No. 3. P. e307–e318. DOI: 10.1210/clinem/dgz141 |
| [25] |
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 |
| [26] |
Weiss L.M., Medeiros L.J., Vickerly A.L. Pathologic features of prognostic significance in adrenocortical carcinoma // Am. J. Surg. Pathol. 1989. Vol. 13, No. 3. P. 202–205. DOI: 10.1097/00000478-198903000-00004 |
| [27] |
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 |
| [28] |
Великанова Л.И. Стрельникова Е.Г., Объедкова Е.В. и др. Получение стероидных профилей мочи больных с инциденталомой надпочечников методом газовой хромато-масс-спектрометрии // Журнал аналитической химии. 2016. Т. 71, № 7. С. 775–781. DOI: 10.7868/S0044450216070161 |
| [29] |
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 |
| [30] |
Ronchi C.L., 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. Vol. 97, No. 12. P. E2251–E2260. DOI: 10.1210/jc.2012-2669 |
| [31] |
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 |
| [32] |
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. Vol. 180, No. 6. P. 387–396. DOI: 10.1530/EJE-18-0923 |
| [33] |
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 |
| [34] |
Kerkhofs T.M., Kerstens M.N., Kema I.P. et al. Diagnostic value of urinary steroid profiling in the evaluation of adrenal tumors // Horm. Cancer. 2015. Vol. 6, No. 4. P. 168–175. DOI: 10.1007/s12672-015-0224-3 |
| [35] |
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 |
| [36] |
Elhassan Y.S., Altieri B., Berhane S. et al. S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study // Eur. J. Endocrinol. 2022. Vol. 186, No. 1. P. 25–36. DOI: 10.1530/EJE-21-0510 |
| [37] |
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 |
| [38] |
Zheng S., Cherniack A.D., Dewal N. et al. Comprehensive pan-genomic characterization of adrenocortical carcinoma // Cancer Cell. 2016. Vol. 29, No. 5. P. 723–736. DOI: 10.1016/j.ccell.2016.04.002 |
| [39] |
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 |
| [40] |
Assié G., Letouzé E., Fassnacht M. et al. Integrated genomic characterization of adrenocortical carcinoma // Nat. Genet. 2014. Vol. 46, No. 6. P. 607–612. DOI: 10.1038/ng.2953 |
| [41] |
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 |
| [42] |
Assié G., Jouinot A., Fassnacht M. et al. Value of molecular classification for prognostic assessment of adrenocortical carcinoma // JAMA Oncol. 2019. Vol. 5, No. 10. P. 1440–1447. DOI: 10.1001/jamaoncol.2019.1558 |
Eco-Vector
/
| 〈 |
|
〉 |