Home A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts
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A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts

  • Usiwoma O. Ataikiru ORCID logo EMAIL logo , Emil R. Iacob , Ingrith Miron , Calin M. Popoiu and Eugen S. Boia
Published/Copyright: December 29, 2021

Abstract

Objectives

Malignant tumor is a top-ranking cause of pediatric (>1-year) mortality in America and Europe. Among pediatric tumors, germ cell tumors (GCT) and gonadal tumors rank fourth (6%) by the Surveillance, Epidemiology, and End Results (SEER) program (seer.cancer.gov). Continuous research on tumor markers harnesses their full potential in tumor detection and management. We evaluated the effectiveness of beta-human chorionic gonadotropin (β-hCG) and Alpha-fetoprotein (AFP) in Romanian children with (para)gonadal tumors and cysts, determining their accuracy in detecting malignancy, tumor-type, stage, complications, prognosis, and treatment response.

Methods

A 10-year retrospective study of AFP and β-hCG in 134 children with cysts and (para)gonadal tumors aged one month to 17 years was performed.

Results

AFP/β-hCG was unelevated in patients with cysts and nonmalignant tumors. Forty-eight/86 patients (43 GCT and 5 non-GCT) with malignant tumors had elevated AFP/β-hCG, 3/48 patients had recurrences, and 25/48 had mixed-GCT (68% had elevated AFP + β-hCG). All 30 patients with Yolk sac tumors (YST) or their components had elevated AFP. Area under the curve, sensitivity and specificity for GCT were: AFP + β-hCG- 0.828, 67.2%, 100%; AFP- 0.813, 64.1%, 100%; and β-hCG- 0.664, 32.8%, 100%. Two patients whose AFP/β-hCG levels remained elevated died. Common mixed-GCT components were YST-80% and embryonal carcinoma-72%. Thirty of 34 metastasis cases were GCT, with 26/34 patients having elevated AFP/β-hCG.

Conclusions

AFP/β-hCG detects malignant GCT and can determine tumor-type. GCT patients with markedly elevated AFP + β-hCG had poor prognosis, especially if recurrence or metastasis was present. Recurrence is unrelated to elevated AFP/β-hCG. The tumor components and quantity present determine AFP/β-hCG values in mixed-GCT.


Corresponding author: Dr. Usiwoma O. Ataikiru, MD, Department of Pediatric Surgery and Orthopedics, “Louis Turcanu” Emergency Childrens Hospital. No. 2, Dr. Iosif Nemoianu Street, Timisoara 300011, Romania; and Department of Pediatric Surgery and Orthopedics, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania, Phone: +40 725435697, E-mail:
All authors contributed significantly to this work.

Acknowledgments

We thank the statistician, Mr. Jeremiah Oyedemi for assisting in the statistical analysis.

  1. Research funding: None declared.

  2. Author contributions: Ingrith Miron, Calin M Popoiu, and Eugen S Boia conceptualized the study, its design, supervised, and revised the article. Usiwoma O Ataikiru and Emil R Iacob compiled, analyzed, and interpreted the data for the article, and also wrote the draft of the article, including literature search. Usiwoma O Ataikiru is the guarantor of the article. All authors are responsible for the accuracy of the data and approved the final version of the article. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed and written consent was obtained from the parents of all children included in this study.

  5. Ethical approval: This study has complied with all relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration and was approved by the Ethics committee of the ‘Louis Turcanu’ Emergency Children’s Clinical Hospital Timisoara (No. 122/2020-16923 on 11.12.2020).

References

1. Heron, MP. Deaths: Leading causes for 2019. Hyattsville, MD (U.S): National Center for Health Statistics; 2021. Division of Vital Statistics Natl Vital Stat Rep 2021, vol 70. July 26.10.15620/cdc:104186Search in Google Scholar

2. Bertuccio, P, Alicandro, G, Malvezzi, M, Carioli, G, Boffetta, P, Levi, F, et al.. Childhood cancer mortality trends in Europe, 1990-2017, with focus on geographic differences. Cancer Epidemiol 2020;67:101768. https://doi.org/10.1016/j.canep.2020.101768.Search in Google Scholar PubMed

3. Lin, X, Wu, D, Zheng, N, Xia, Q, Han, Y. Gonadal germ cell tumors in children: a retrospective review of a 10-year single-center experience. Medicine 2017;96:e7386. https://doi.org/10.1097/MD.0000000000007386.Search in Google Scholar PubMed PubMed Central

4. Sharma, S. Tumor markers in clinical practice: general principles and guidelines. Indian journal of medical and paediatric oncology. Indian J Med Paediatr Oncol 2009;30:1. https://doi.org/10.4103/0971-5851.56328.Search in Google Scholar PubMed PubMed Central

5. Milose, JC, Filson, CP, Weizer, AZ, Hafez, KS, Montgomery, JS. Role of biochemical markers in testicular cancer: diagnosis, staging, and surveillance. Open Access J Urol 2012;4:1–8. https://doi.org/10.2147/OAJU.S15063.Search in Google Scholar PubMed PubMed Central

6. Çorapçıoğlu, F, Türker, G, Aydoğan, A, Sarper, N, Duman, C, Arısoy, AE. Serum alpha fetoprotein levels in healthy full-term neonates and infants. Marmara Med J 2004;17:1–7.Search in Google Scholar

7. Tomasi, TBJr. Structure and function of alpha-fetoprotein. Annu Rev Med 1977;28:453–65. https://doi.org/10.1146/annurev.me.28.020177.002321.Search in Google Scholar PubMed

8. Bakker, J, De Mees, C, Douhard, Q, Balthazart, J, Gabant, P, Szpirer, J, et al.. Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens. Nat Neurosci 2006;9:220–6. https://doi.org/10.1038/nn1624.Search in Google Scholar PubMed

9. Fournier, T, Guibourdenche, J, Evain-Brion, D. hCGs: different sources of production, different glycoforms and functions. Placenta 2015;36:S60–5. https://doi.org/10.1016/j.placenta.2015.02.002.Search in Google Scholar PubMed

10. Stockton, L, Green, E, Kaur, B, De Winton, E. Non-gestational choriocarcinoma with widespread metastases presenting with type 1 respiratory failure in a 39-year-old female: case report and review of the literature. Case Rep Oncol 2018;11:151–8. https://doi.org/10.1159/000486639.Search in Google Scholar PubMed PubMed Central

11. Lempiäinen, A, Sankila, A, Hotakainen, K, Haglund, C, Blomqvist, C, Stenman, UH. Expression of human chorionic gonadotropin in testicular germ cell tumors. Urol Oncol 2014;32:727–34. https://doi.org/10.1016/j.urolonc.2013.11.007.Search in Google Scholar PubMed

12. Agarwal, S, Tu, DD, Austin, PF, Scheurer, ME, Karaviti, LP. Testosterone versus hCG in hypogonadotropic hypogonadism–comparing clinical effects and evaluating current practice. Glob Pediatr Health 2020;7:1–9. https://doi.org/10.1177/2333794x20958980.Search in Google Scholar

13. Theofanakis, C, Drakakis, P, Besharat, A, Loutradis, D. Human chorionic gonadotropin: the pregnancy hormone and more. Int J Mol Sci 2017;18:1059. https://doi.org/10.3390/ijms18051059.Search in Google Scholar

14. Duffy, KA, Cohen, JL, Elci, OU, Kalish, JM. Development of the serum α-fetoprotein reference range in patients with Beckwith-Wiedemann spectrum. J Pediatr 2019;212:195–200. https://doi.org/10.1016/j.jpeds.2019.05.051.Search in Google Scholar

15. Glick, PL, Pohlson, EC, Resta, R, Payne, C, Mosbarger, H, Luthy, DA, et al.. Maternal serum alpha-fetoprotein is a marker for fetal anomalies in pediatric surgery. J Pediatr Surg 1988;23:16–20. https://doi.org/10.1016/s0022-3468(88)80531-1.Search in Google Scholar

16. Kölbl, AC, Schlenk, K, Behrendt, N, Andergassen, U. The importance of hCG in human endometrial adenocarcinoma and breast cancer. Int J Biol Markers 2018;33:33–9. https://doi.org/10.5301/ijbm.5000290.Search in Google Scholar PubMed

17. Chao, WT, Liu, CH, Lai, CR, Chen, YJ, Chuang, CM, Wang, PH. Alpha-fetoprotein-producing ovarian clear cell adenocarcinoma with fetal gut differentiation: a rare case report and literature review. J Ovarian Res 2018;11:1–7. https://doi.org/10.1186/s13048-018-0426-8.Search in Google Scholar PubMed PubMed Central

18. Badve, SS, Saxena, R, Soman, CS, Kiri, VM, Raghuvanshi, SR, Patoria, NK. Alpha-fetoprotein production by rhabdomyosarcoma of the urinary bladder. Indian J Cancer 1992;29:177–80.Search in Google Scholar

19. Hu, M, Guan, H, Lau, CC, Terashima, K, Jin, Z, Cui, L, et al.. An update on the clinical diagnostic value of β-hCG and αFP for intracranial germ cell tumors. Eur J Med Res 2016;21:1–11. https://doi.org/10.1186/s40001-016-0204-2.Search in Google Scholar PubMed PubMed Central

20. Kinoshita, Y, Yamasaki, F, Usui, S, Amatya, VJ, Tominaga, A, Sugiyama, K, et al.. Solitary Langerhans cell histiocytosis located in the neurohypophysis with a positive titer HCG-β in the cerebrospinal fluid. Childs Nerv Syst 2016;32:901–4. https://doi.org/10.1007/s00381-015-2949-2.Search in Google Scholar PubMed

21. Barlow, LJ, Badalato, GM, McKiernan, JM. Serum tumor markers in the evaluation of male germ cell tumors. Nat Rev Urol 2010;7:610. https://doi.org/10.1038/nrurol.2010.166.Search in Google Scholar PubMed

22. Tahara, H, Hirokawa, T, Oyama, T, Naganuma, A, Maruta, S, Ban, S, et al.. Gastric yolk sac tumor complicated with beta-human chorionic gonadotropin-producing metastases. Intern Med 2008;47:2145–9. https://doi.org/10.2169/internalmedicine.47.1385.Search in Google Scholar PubMed

23. Huang, SC, Chen, HC, Kurman, RJ, Yang, YS, Wen, HK, Hsieh, CY, et al.. Secretion of human chorionic gonadotropin and α-fetoprotein by an ovarian germ cell tumor of apparent yolk sac origin. Gynecol Oncol 1984;18:240–6. https://doi.org/10.1016/0090-8258(84)90032-5.Search in Google Scholar

24. Baker, PM, Oliva, E. Immature teratoma. Germ cell tumors of the ovary. In: Chapter 13, Nucci, MR, Oliva, E, Goldblum, JR, editors. Gynecologic pathology. Philadelphia: Elsevier; 2009:501–38 pp.10.1016/B978-044306920-8.50017-1Search in Google Scholar

25. Murray, MJ, Nicholson, JC. α-Fetoprotein. Arch Dis Child Educ Pract Ed 2011;96:141–7. https://doi.org/10.1136/adc.2011.213181.Search in Google Scholar

26. Ferraro, S, Panzeri, A, Braga, F, Panteghini, M. Serum α-fetoprotein in pediatric oncology: not a children’s tale. Clin Chem Lab Med 2019;57:783–97. https://doi.org/10.1515/cclm-2018-0803.Search in Google Scholar

27. Fischerova, D, Zikan, M, Dundr, P, Cibula, D. Diagnosis, treatment, and follow-up of borderline ovarian tumors. Oncologist 2012;17:1515. https://doi.org/10.1634/theoncologist.2012-0139.Search in Google Scholar

28. Asano, T, Kawakami, MP, Okuno, T, Tsujii, T, Nemoto, T, Kageyama, Y, et al.. Malignant transformation in a mature testicular teratoma left untreated for more than 50 years since childhood. Scand J Urol Nephrol 2003;37:177–8. https://doi.org/10.1080/00365590310008947.Search in Google Scholar

29. Siegelman, ES. MRI of the female pelvis. In: Chapter 7, Saunders, WB, editors. Body MRI, 1st ed. Philadelphia: Elsevier; 2005:269–342 pp.10.1016/B978-0-7216-3740-2.50012-1Search in Google Scholar

30. Pressley, RH, Muntz, HG, Falkenberry, S, Rice, LW. Serum lactic dehydrogenase as a tumor marker in dysgerminoma. Gynecol Oncol 1992;44:281–3. https://doi.org/10.1016/0090-8258(92)90058-q.Search in Google Scholar

31. Göcze, P, Vahrson, H. Ovarian carcinoma antigen (CA 125) and ovarian cancer (clinical follow-up and prognostic studies). Orv Hetil 1993;134:915–8.Search in Google Scholar

32. Dieckmann, KP, Radtke, A, Spiekermann, M, Balks, T, Matthies, C, Becker, P, et al.. Serum levels of microRNA miR-371a-3p: a sensitive and specific new biomarker for germ cell tumours. Eur Urol 2017;71:213–20. https://doi.org/10.1016/j.eururo.2016.07.029.Search in Google Scholar PubMed

33. Piao, J, Lafin, JT, Scarpini, CG, Nuño, MM, Syring, I, Dieckmann, KP, et al.. A multi-institutional pooled analysis demonstrates that circulating miR-371a-3p alone is sufficient for testicular malignant germ cell tumor diagnosis. Clin Genitourin Cancer 2021;19:469–79. https://doi.org/10.1016/j.clgc.2021.08.006.Search in Google Scholar PubMed PubMed Central

34. Mirimanoff, R, Sinzig, M, Krüger, M, Miralbell, R, Thöni, A, Ries, G, et al.. Prognosis of human chorionic gonadotropin-producing seminoma treated by postoperative radiotherapy. Int J Radiat Oncol Biol Phys 1993;27:17–23. https://doi.org/10.1016/0360-3016(93)90416-s.Search in Google Scholar

35. Akan, S, Ediz, C, Tavukcu, HH, Ozgun, A, Yilmaz, O. The clinical significance of seminoma component in testicular mixed germ cell tumour. Urol Int 2020;104:489–96. https://doi.org/10.1159/000506780.Search in Google Scholar PubMed

36. Suster, S, Moran, CA. Teratoma with additional malignant components: Mediastinum. In: Chapter 17, Weidner, N, Cote, RJ, Suster, S, Weiss, LM, editors. Modern surgical pathology, 2nd ed. London: Elsevier; 2009:454–516 pp.10.1016/B978-1-4160-3966-2.00017-5Search in Google Scholar

37. Williamson, SR, Delahunt, B, Magi‐Galluzzi, C, Algaba, F, Egevad, L, Ulbright, TM, et al.. The World Health Organization 2016 classification of testicular germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology 2017;70:335–46. https://doi.org/10.1111/his.13102.Search in Google Scholar PubMed

38. Tiwary, B, Sinha, H, Pandey, V. Malignant mixed germ cell tumour of ovary: a rare case report. Int J Reprod Contracept Obstet Gynecol 2015;4:511–3. https://doi.org/10.5455/2320-1770.ijrcog20150450.Search in Google Scholar

39. Kurman, RJ, Scardino, PT, McIntire, KR, Waldmann, TA, Javadpour, N, Norris, HJ. Malignant germ cell tumors of the ovary and testis. An immunohistologic study of 69 cases. Ann Clin Lab Sci 1979;9:462–6.Search in Google Scholar

40. Alvarado-Cabrero, I, Hernández-Toriz, N, Paner, GP. Clinicopathologic analysis of choriocarcinoma as a pure or predominant component of germ cell tumor of the testis. Am J Surg Pathol 2014;38:111–8. https://doi.org/10.1097/pas.0b013e3182a2926e.Search in Google Scholar PubMed

41. Gilligan, TD, Hayes, DF, Seidenfeld, J, Temin, S. ASCO clinical practice guideline on uses of serum tumor markers in adult males with germ cell tumors. J Oncol Pract 2010;6:199. https://doi.org/10.1200/jop.777010.Search in Google Scholar PubMed PubMed Central

Received: 2021-06-05
Accepted: 2021-12-06
Published Online: 2021-12-29
Published in Print: 2022-03-28

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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