Anti-Müllerian hormone: a potentially useful biomarker for the diagnosis of canine Sertoli cell tumours

BMC Veterinary Research

Ulrika Dreimanis²  Bodil S. Holst¹ 

[1] Centre for Reproductive Biology in Uppsala, Swedish University of Agricultural Sciences (SLU), Uppsala, SE-750 07, Sweden;Department of Small Animals, Helsingborg Referral Animal Hospital, Helsingborg, SE-254 66, Sweden

关键词: Testis;    Sertoli cell;    Neoplasia;    Dog;    Anti-Müllerian hormone;   

Others  :  1224418
DOI  :  10.1186/s12917-015-0487-5

 received in 2014-12-19, accepted in 2015-07-16,  发布年份 2015

【 摘 要 】

Background

Testicular tumours are common in dogs and in many cases do not give rise to clinical signs. In other cases, signs of feminization, hyperpigmentation or alopecia may be observed, most commonly associated with Sertoli cell tumours (SCT). Although these signs are often associated with elevated concentrations of oestradiol, analysis of oestradiol may give inconclusive results due to large variations among individuals. Other biomarkers are therefore needed. Anti-Müllerian hormone (AMH) is expressed by the Sertoli cell. In humans, AMH has been shown to be a specific marker of Sertoli cell origin in gonadal tumours. Using immunohistochemistry, AMH has been shown to be a useful marker of immature and neoplastic Sertoli cells in dogs. The aim of the present study was to evaluate the clinical relevance of AMH analysis in peripheral blood in the diagnostic workup of dogs with suspected testicular tumours.

Results

Blood was collected from 20 dogs with a palpable testicular mass and from 27 healthy controls. Serum was analysed for oestradiol-17β using a RIA and for AMH using an ELISA. The Mann–Whitney U test was used to compare hormone concentrations between different groups.

All control dogs had AMH concentrations ≤ 10 ng/mL, except one outlier that had a concentration of 43 ng/mL. Six dogs with SCT or mixed tumours containing SCT had AMH concentrations higher than 22 ng/mL, significantly higher than AMH concentrations in control dogs (P = 0.0004). Concentrations between 10 and 22 ng/mL were found in about half of the dogs with non-neoplastic testicular pathologies or with testicular tumours other than SCTs. Age did not significantly affect concentrations of AMH in the control dogs.

Conclusion

AMH was shown to be a promising biomarker for the diagnosis of Sertoli cell tumours in dogs.

【 授权许可】

   
2015 Holst and Dreimanis.

【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】

• [1]Reifinger M. Statistical studies of the occurrence of testicular neoplasms in domestic mammals. Zentralbl Veterinarmed A. 1988; 35(1):63-72.
• [2]Dow C. Testicular tumours in the dog. J Comp Pathol. 1962; 72:247-265.
• [3]Nodtvedt A, Gamlem H, Gunnes G, Grotmol T, Indrebo A, Moe L. Breed differences in the proportional morbidity of testicular tumours and distribution of histopathologic types in a population-based canine cancer registry. Vet Comp Oncol. 2011; 9(1):45-54.
• [4]Grieco V, Riccardi E, Greppi GF, Teruzzi F, Iermano V, Finazzi M. Canine testicular tumours: a study on 232 dogs. J Comp Pathol. 2008; 138(2–3):86-89.
• [5]Moller H. Trends in sex-ratio, testicular cancer and male reproductive hazards: are they connected? APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 1998; 106(1):232-238.
• [6]Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001; 16(5):972-978.
• [7]Grieco V, Riccardi E, Veronesi MC, Giudice C, Finazzi M. Evidence of testicular dysgenesis syndrome in the dog. Theriogenology. 2008; 70(1):53-60.
• [8]Liao AT, Chu PY, Yeh LS, Lin CT, Liu CH. A 12-year retrospective study of canine testicular tumors. J Vet Med Sci. 2009; 71(7):919-923.
• [9]Dreimanis U, Vargmar K, Falk T, Cigut M, Toresson L. Evaluation of preputial cytology in diagnosing oestrogen producing testicular tumours in dogs. J Small Anim Pract. 2012; 53(9):536-541.
• [10]Reif JS, Maguire TG, Kenney RM, Brodey RS. A cohort study of canine testicular neoplasia. J Am Vet Med Assoc. 1979; 175(7):719-723.
• [11]England GC. Ultrasonographic diagnosis of non-palpable Sertoli cell tumours in infertile dogs. J Small Anim Pract. 1995; 36(11):476-480.
• [12]Mischke R, Meurer D, Hoppen HO, Ueberschar S, Hewicker-Trautwein M. Blood plasma concentrations of oestradiol-17beta, testosterone and testosterone/oestradiol ratio in dogs with neoplastic and degenerative testicular diseases. Res Vet Sci. 2002; 73(3):267-272.
• [13]Peters MA, de Jong FH, Teerds KJ, de Rooij DG, Dieleman SJ, van Sluijs FJ. Ageing, testicular tumours and the pituitary-testis axis in dogs. J Endocrinol. 2000; 166(1):153-161.
• [14]Gopinath D, Draffan D, Philbey AW, Bell R. Use of intralesional oestradiol concentration to identify a functional pulmonary metastasis of canine sertoli cell tumour. J Small Anim Pract. 2009; 50(4):198-200.
• [15]Sherding RG, Wilson GP, Kociba GJ. Bone marrow hypoplasia in eight dogs with Sertoli cell tumor. J Am Vet Med Assoc. 1981; 178(5):497-501.
• [16]Kasbohm C, Saar C. [Bone-marrow damage due to estrogen in dogs with testicular neoplasms]. Tierarztliche Praxis. 1975; 3(2):225-229.
• [17]Edwards DF. Bone marrow hypoplasia in a feminized dog with a Sertoli cell tumor. J Am Vet Med Assoc. 1981; 178(5):494-496.
• [18]Josso N, di Clemente N. TGF-beta Family Members and Gonadal Development. Trends in endocrinology and metabolism: TEM. 1999; 10(6):216-222.
• [19]Josso N, di Clemente N, Gouedard L. Anti-Mullerian hormone and its receptors. Mol Cell Endocrinol. 2001; 179(1–2):25-32.
• [20]Rey R, Sabourin JC, Venara M, Long WQ, Jaubert F, Zeller WP, Duvillard P, Chemes H, Bidart JM. Anti-Mullerian hormone is a specific marker of sertoli- and granulosa-cell origin in gonadal tumors. Hum Pathol. 2000; 31(10):1202-1208.
• [21]Banco B, Veronesi MC, Giudice C, Rota A, Grieco V. Immunohistochemical evaluation of the expression of anti-Mullerian hormone in mature, immature and neoplastic canine Sertoli cells. J Comp Pathol. 2012; 146(1):18-23.
• [22]Nelson SM, La Marca A. The journey from the old to the new AMH assay: how to avoid getting lost in the values. Reprod Biomed Online. 2011; 23(4):411-420.
• [23]Brodin T, Hadziosmanovic N, Berglund L, Olovsson M, Holte J. Antimullerian hormone levels are strongly associated with live-birth rates after assisted reproduction. J Clin Endocrinol Metab. 2013; 98(3):1107-1114.
• [24]Rico C, Drouilhet L, Salvetti P, Dalbies-Tran R, Jarrier P, Touze JL, Pillet E, Ponsart C, Fabre S, Monniaux D. Determination of anti-Mullerian hormone concentrations in blood as a tool to select Holstein donor cows for embryo production: from the laboratory to the farm. Reprod Fertil Dev. 2012; 24(7):932-944.
• [25]Place NJ, Hansen BS, Cheraskin JL, Cudney SE, Flanders JA, Newmark AD, Barry B, Scarlett JM. Measurement of serum anti-Mullerian hormone concentration in female dogs and cats before and after ovariohysterectomy. J Vet Diagn Invest. 2011; 23(3):524-527.
• [26]Kumar A, Kalra B, Patel A, McDavid L, Roudebush WE. Development of a second generation anti-Mullerian hormone (AMH) ELISA. J Immunol Methods. 2010; 362(1–2):51-59.
• [27]Kennedy PC, Cullen JM, Edwards JF, Goldschmidt MH, Larsen S, Munson L, Nielsen S. Histological classification of tumors of the genital system of domestic animals. In: World health Organization International Histological Classification of Tumors of Domestic Animals. Volume IV, 2 edn. Armed Forces Institute of pathology, Washington DC; 1998: p.17-18.
• [28]Ano H, Hidaka Y, Katamoto H. Evaluation of anti-Mullerian hormone in a dog with a Sertoli cell tumour. Vet Dermatol. 2014; 25(2):142-145.
• [29]Axner E, Strom Holst B. Concentrations of anti-Mullerian hormone in the domestic cat. Relation with spay or neuter status and serum estradiol. Theriogenology. 2015; 83(5):817-821.
• [30]Giudice C, Banco B, Veronesi MC, Ferrari A, Di Nardo A, Grieco V. Immunohistochemical expression of markers of immaturity in sertoli and seminal cells in canine testicular atrophy. J Comp Pathol. 2014; 150(2–3):208-215.
• [31]Chong YH, Dennis NA, Connolly MJ, Teh R, Jones GT, van Rij AM, Farrand S, Campbell AJ, McLennan IS. Elderly men have low levels of anti-Mullerian hormone and inhibin B, but with high interpersonal variation: a cross-sectional study of the sertoli cell hormones in 615 community-dwelling men. PLoS One. 2013; 8(8):e70967.
• [32]Frank LA, Rohrbach BW, Bailey EM, West JR, Oliver JW. Steroid hormone concentration profiles in healthy intact and neutered dogs before and after cosyntropin administration. Domest Anim Endocrinol. 2003; 24(1):43-57.
• [33]Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001; 45(3 Suppl):S116-124.
• [34]Frank LA, Mullins R, Rohrbach BW. Variability of estradiol concentration in normal dogs. Vet Dermatol. 2010; 21(5):490-493.
• [35]Grinspon RP, Rey RA. New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker. Arquivos brasileiros de endocrinologia e metabologia. 2011; 55(8):512-519.
• [36]Josso N, Rey RA, Picard JY. Anti-mullerian hormone: a valuable addition to the toolbox of the pediatric endocrinologist. Int J Endocrinol. 2013; 2013:674105.
• [37]Matuszczak E, Hermanowicz A, Komarowska M, Debek W. Serum AMH in Physiology and Pathology of Male Gonads. Int J Endocrinol. 2013; 2013:128907.
• [38]Siegel ET, Forchielli E, Dorfman RI, Brodey RS, Prier JE. An estrogen study in the feminized dog with testicular neoplasia. Endocrinology. 1967; 80(2):272-277.
• [39]Claes A, Ball BA, Almeida J, Corbin CJ, Conley AJ. Serum anti-Mullerian hormone concentrations in stallions: developmental changes, seasonal variation, and differences between intact stallions, cryptorchid stallions, and geldings. Theriogenology. 2013; 79(9):1229-1235.