Somatostatin receptor expression in adrenocortical carcinomas

Cover Page
Open Access Open Access
Restricted Access Subscription Access


Background. Adrenocortical carcinoma (ACC) is a rare malignant tumor characterized by an annual incidence of 0.5—2 cases per million population. Surgery is the-first line treatment for ACC. When total tumor resection is not possible due to its proliferation or progression, mitotane (o,p’DDD) is used. In this case, stabilization and partial response (as assessed by RECIST criteria) was observed only in 48.7% of cases, necessitating the search for new therapeutic targets.

Objective — the study was aimed at assessing the somatostatin receptor expression in adrenocortical carcinomas and adrenal cortex tumors with uncertain malignant potential.

Material and methods. Surgical material from adrenocortical tumors of 13 patients (4 males and 9 females aged from 28 to 68 years) was used. In all cases, the diagnosis was verified by morphological and immunohistochemical (IHC) studies: ACC was detected in 10 cases (including 1 case of ACC liver metastasis), oncocytic carcinoma — 1 case, oncocytoma with uncertain malignant potential — 2 cases. Morphological assessment of ACC was carried out according to Weiss criteria (for ACC tumors) and Lin—Weiss—Bisceglia criteria (for oncocytic neoplasms of the adrenal cortex). IHC study was carried out with antibodies to the spectrum of adrenal cortex-specific markers, as well as Ki-67 and somatostatin receptors 2 and 5 (SSTR2 and SSTR5).

Results. The expression of SSTR2 and/or 5 was detected in 8 (61.5%) of 13 cases of ACC. Isolated SSTR2 expression was observed in 4 cases (4/13), while SSTR5 expression was observed in 6 cases (6/10). In 2 cases (2/10), co-expression of both receptor types was observed. SSTR expression was observed both in ACC and ACC liver metastasis, as well as in oncocytic ACC.

Conclusion. SSTR2 and/or 5 expression in ACC tissue expands diagnostic and prognostic capabilities for this pathology.

Iya A. Voronkova

Author for correspondence.
ORCID iD: 0000-0001-6687-3240
SPIN-code: 9685-1371
Endocrinology Research Centre; Moscows regional research clinical institute n.a. M.F. Vladimirskiy
Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036; 61/2, Shepkina street, Moscow, 129110


Larisa E. Gurevch
ORCID iD: 0000-0002-9731-3649
SPIN-code: 8615-0038
Moscows regional research clinical institute n.a. M.F. Vladimirskiy
Russian Federation, 61/2, Shepkina street, Moscow, 129110

PhD, Professor

Timur A. Britvin
ORCID iD: 0000-0001-6160-1342
SPIN-code: 1207-2935
Moscows regional research clinical institute n.a. M.F. Vladimirskiy
Russian Federation, 61/2, Shepkina street, Moscow, 129110


Alexey V. Krivosheev
ORCID iD: 0000-0003-3643-6810
SPIN-code: 6166-8406
Moscows regional research clinical institute n.a. M.F. Vladimirskiy
Russian Federation, 61/2, Shepkina street, Moscow, 129110

Department of  Endocrine Surgery

Galina A. Mel’nichenko
ORCID iD: 0000-0002-5634-7877
SPIN-code: 5873-2280
Endocrinology Research Centre
Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD, Professor

  • Ромащенко П.Н., Майстренко Н.А., Орлова Р.В., Бабич А.И. Результаты диагностики и лечения адренокортикального рака. // Вестник хирургии имени И.И. Грекова. — 2015. — Т. 174. — №3. — С. 29-39. [Romashchenko PN, Maystrenko NA, Orlova RV, Babich AI. Results of diagnostics and treatment of adrenocortical cancer. Vestn Khir Im I I Grek. 2015;174(3):29-39. (In Russ.)].
  • Bilimoria KY, Shen WT, Elaraj D, et al. Adrenocortical carcinoma in the United States. Cancer. 2008;113(11):3130-3136. doi: 10.1002/cncr.23886.
  • Kim Y, Margonis GA, Prescott JD, et al. Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability. Ann Surg. 2017;265(1):197-204. doi: 10.1097/SLA.0000000000001527.
  • Коломейцева А.А., Горбунова В.А., Переводчикова Н.И. Современное состояние проблемы лечения адренокортикального рака. // Российский онкологический журнал. — 2014. — T. 19. — №6. — С. 44-48. [Kolomeytseva AA, Gorbunova VA, Perevodchikova NI. The problem of adrenocortical cancer therapy. Russian journal of oncology. 2014;19(6):44-48. (In Russ.)].
  • Icard P, Goudet P, Charpenay C, et al. Adrenocortical carcinomas: surgical trends and results of a 253 patient series from the French Association of Endocrine Surgeons study group. World J Surg. 2001;25(7):891-897. doi: 10.1007/s00268-001-0047-y.
  • Дедов И.И., Мельниченко Г.А., Бельцевич Д.Г., и др. Опыт применения митотана в комплексном лечении адренокортикального рака. // Российский онкологический журнал. — 2016. — T. 21. — №6. — С. 284-292. [Dedov II, Melnichenko GA, Beltsevich DG, et al. Experience of the use of mitotan in the combined treatment of adrenocortical cancer. Russian journal of oncology. 2016;21(6):284-292. (In Russ.)]. doi: 10.18821/1028-9984-2016-21-6-284-292.
  • Creemers SG, Hofland LJ, Korpershoek E, et al. Future directions in the diagnosis and medical treatment of adrenocortical carcinoma. Endocr Relat Cancer. 2016;23(1):R43-R69. doi: 10.1530/ERC-15-0452.
  • Mariniello B, Finco I, Sartorato P, et al. Somatostatin receptor expression in adrenocortical tumors and effect of a new somatostatin analog SOM230 on hormone secretion in vitro and in ex vivo adrenal cells. J Endocrinol Invest. 2011;34(6):e131-e138. doi: 10.3275/7324.
  • Germano A, Rapa I, Duregon E, et al. Tissue Expression and pharmacological in vitro analyses of mTOR and SSTR pathways in adrenocortical carcinoma. Endocr Pathol. 2017;28(2):95-102. doi: 10.1007/s12022-017-9473-8.
  • Lau SK, Weiss LM. The Weiss system for evaluating adrenocortical neoplasms: 25 years later. Hum Pathol. 2009;40(6):757-768. doi: 10.1016/j.humpath.2009.03.010.
  • Lam AK. Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours. Endocr Pathol. 2017. doi: 10.1007/s12022-017-9484-5.
  • Giordano TJ, Chrousos GP, de Krijger RB, et al. Adrenal cortical carcinoma. In: Lloyd RV, Osamura RY, Kloppel G, Rosai J, editors. WHO classification of tumors of endocrine organs. Lyon: IARC; 2017;163-168.
  • Volante M, Brizzi MP, Faggiano A, et al. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol. 2007;20(11):1172-1182. doi: 10.1038/modpathol.3800954.
  • Weissferdt A, Phan A, Suster S, Moran CA. Adrenocortical carcinoma: a comprehensive immunohistochemical study of 40 cases. Appl Immunohistochem Mol Morphol. 2014;22(1):24-30. doi: 10.1097/PAI.0b013e31828a96cf.
  • McCluggage WG, Burton J, Maxwell P, Sloan JM. Immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin. J Clin Pathol. 1998;51(2):114-116. doi: 10.1136/jcp.51.2.114.
  • Giordano TJ, Chrousos GP, de Kawashima A, et al. Adrenal cortical adenoma. In: Lloyd RV, Osamura RY, Kloppel G, Rosai J, editors. WHO classification of tumors of endocrine organs. Lyon: IARC; 2017;169-172.
  • Unger N, Serdiuk I, Sheu SY, et al. Immunohistochemical localization of somatostatin receptor subtypes in benign and malignant adrenal tumours. Clin Endocrinol (Oxf). 2008;68(6):850-857. doi: 10.1111/j.1365-2265.2007.03124.x.
  • de Bruin C, Feelders RA, Waaijers AM, et al. Differential regulation of human dopamine D2 and somatostatin receptor subtype expression by glucocorticoids in vitro. J Mol Endocrinol. 2008;42(1):47-56. doi: 10.1677/jme-08-011.
  • Гуревич Л.Е., Корсакова Н.А., Воронкова И.А., и др. Иммуногистохимическое определение экспрессии рецепторов к соматостатину 1, 2А, 3 и 5-го типов в нейроэндокринных опухолях различной локализации и степени злокачественности. // Альманах клинической медицины. — 2016. — T. 44. — №4. — С. 378-390. [Gurevich LE, Korsakova NA, Voronkova IA, et al. Immunohistochemecal determination of expression of somatostatin receptors type 1, 2A,3 and 5 in neuroendocrine tumots of various localization and grade. Almanac of clinical medicine. 2016;44(4):378-390. (In Russ.)]. doi: 10.18786/2072-0505-2016-44-4-378-390.
  • Papathomas TG, Pucci E, Giordano TJ, et al. An International Ki-67 Reproducibility Study in Adrenal Cortical Carcinoma. Am J Surg Pathol. 2016;40(4):569-576. doi: 10.1097/PAS.0000000000000574.
  • Pandha HS, Harrington K, Saini S, et al. Secretory symptoms from metastatic adrenal cortical carcinoma responding to octreotide. Postgrad Med J. 1995;71(834):229-230. doi: 10.1136/pgmj.71.834.229.
  • Chan NN, Isaacs AJ. Lack of response to octreotide in Cushing’s syndrome due to metastatic adrenocortical carcinoma. Postgrad Med J. 1999;75(880):96-98. doi: 10.1136/pgmj.75.880.96.
  • Florio T. Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci. 2008;13:822-840.
  • Dasgupta P. Somatostatin analogues: multiple roles in cellular proliferation, neoplasia, and angiogenesis. Pharmacol Ther. 2004;102(1):61-85. doi: 10.1016/j.pharmthera.2004.02.002.
  • Ziegler CG, Brown JW, Schally AV, et al. Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: antiproliferative effects of peptide analogues. Proc Natl Acad Sci USA. 2009;106(37):15879-15884. doi: 10.1073/pnas.0907843106.

Supplementary files

Supplementary Files Action
1. Fig. 1. Evaluation of the expression of receptors for somatostatin in scores in adrenal cortex formations. а - 3 points: complete membrane staining of more than 50% of tumor cells (× 400); b - 2 points: membrane-cytoplasmic staining, mainly incomplete membrane expression in less than 50% of tumor cells (× 400); c - 1 point: staining only the cytoplasm (× 400); g - 0 points: no expression (× 400). View (1MB) Indexing metadata
2. Fig. 2. Expression of somatostatin receptors in AKP. №1 (а-в). AKR solid-trabecular structure (hematoxylin and eosin, × 200); b - focal cytoplasmic expression of PCST2 (1 point) (× 200); c - diffuse full membrane expression of PCST5 (3 points) (× 100). №2 (г-е). g - AKP solid structure (hematoxylin and eosin, × 200); d - diffuse cytoplasmic and incomplete membrane expression of PCST2 (2 points) (× 200); e-incomplete membrane-cytoplasmic expression of PCST5 (2 points) (× 200). №3 (ж-и). g - oncocyte AKP (hematoxylin and eosin, × 200); h - expression of RCST2 is absent (0 points) (× 200); and - diffuse full membrane expression of PCST5 (3 points) (× 200). № 4 (к-м). k - metastasis of AKP in the liver (hematoxylin and eosin, × 100); l - diffuse incomplete membrane-cytoplasmic expression of PCST2 (2 points) (× 200); m - diffuse total membrane expression of PCST5 (3 points) (× 200). View (4MB) Indexing metadata


Abstract - 585

PDF (Russian) - 107

Remote (Russian) - 227

PDF (English) - 0

Remote (English) - 0


Copyright (c) 2018 Voronkova I.A., Gurevch L.E., Britvin T.A., Krivosheev A.V., Mel’nichenko G.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.