BACKGROUND: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. METHODS: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. RESULTS: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5-10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. CONCLUSION: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.

Department of Oncological Pathology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Pathology 1st Faculty of Medicine Charles University and General University Hospital Prague Studničkova 2 Prague 2 12800 Czech Republic

Department of Pathology and Molecular Medicine 3rd Faculty of Medicine Charles University Thomayer University Hospital Prague Czech Republic

Department of Pathology Bulovka University Hospital Prague Czech Republic

Department of Pathology Charles University 3rd Faculty of Medicine University Hospital Královské Vinohrady Prague 10034 Czech Republic

Department of Pathology Faculty of Medicine University of Debrecen Debrecen 4032 Hungary

Department of Pathology The Regional Hospital Pardubice Pardubice Czech Republic

Department of Pathology University Hospital Brno and Medical Faculty Masaryk University Brno Czech Republic

Department of Pathology University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

Division of Gynecologic Oncology Department of Surgical Oncology Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University Brno Czech Republic

Šikl's Department of Pathology The Faculty of Medicine Faculty Hospital in Pilsen Charles University Pilsen Czech Republic

The Fingerland Department of Pathology Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Hradec Králové Czech Republic

See more in PubMed

Cassimeris L. The oncoprotein 18/stathmin family of microtubule destabilizers. Curr Opin Cell Biol. 2002;14(1):18–24. 10.1016/S0955-0674(01)00289-7 PubMed DOI

Watanabe A, Suzuki H, Yokobori T, et al. Stathmin1 regulates p27 expression, proliferation and drug resistance, resulting in poor clinical prognosis in cholangiocarcinoma. Cancer Sci. 2014;105(6):690–6. 10.1111/cas.12417 PubMed DOI PMC

Rowlands DC, Williams A, Jones NA, et al. Stathmin expression is a feature of proliferating cells of most, if not all, cell lineages. Lab Invest. 1995;72(1):100–13. PubMed

Bièche I, Maucuer A, Laurendeau I, et al. Expression of stathmin family genes in human tissues: non-neural-restricted expression for SCLIP. Genomics. 2003;81(4):400–10. 10.1016/S0888-7543(03)00031-4 PubMed DOI

Dong B, Mu L, Qin X, et al. Stathmin expression in glioma-derived microvascular endothelial cells: a novel therapeutic target. Oncol Rep. 2012;27(3):714–8. PubMed

Nie W, Xu MD, Gan L, Huang H, Xiu Q, Li B. Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer. Lab Invest. 2015;95(1):56–64. 10.1038/labinvest.2014.124 PubMed DOI

Kouzu Y, Uzawa K, Koike H, et al. Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis. Br J Cancer. 2006;94(5):717–23. 10.1038/sj.bjc.6602991 PubMed DOI PMC

Han G, Wu Z, Zhao N, et al. Overexpression of stathmin plays a pivotal role in the metastasis of esophageal squamous cell carcinoma. Oncotarget. 2017;8(37):61742–60. 10.18632/oncotarget.18687 PubMed DOI PMC

Jeon TY, Han ME, Lee YW, et al. Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells. Br J Cancer. 2010;102(4):710–8. 10.1038/sj.bjc.6605537 PubMed DOI PMC

Ke B, Wu LL, Liu N, Zhang RP, Wang CL, Liang H. Overexpression of stathmin 1 is associated with poor prognosis of patients with gastric cancer. Tumour Biol. 2013;34(5):3137–45. 10.1007/s13277-013-0882-0 PubMed DOI

Suzuki K, Watanabe A, Araki K, et al. High STMN1 expression is Associated with Tumor differentiation and metastasis in clinical patients with pancreatic Cancer. Anticancer Res. 2018;38(2):939–44. PubMed

Gan L, Guo K, Li Y, et al. Up-regulated expression of stathmin may be associated with hepatocarcinogenesis. Oncol Rep. 2010;23(4):1037–43. PubMed

Tan HT, Wu W, Ng YZ, et al. Proteomic analysis of colorectal cancer metastasis: stathmin-1 revealed as a player in cancer cell migration and prognostic marker. J Proteome Res. 2012;11(2):1433–45. 10.1021/pr2010956 PubMed DOI

Curmi PA, Noguès C, Lachkar S, et al. Overexpression of stathmin in breast carcinomas points out to highly proliferative tumours. Br J Cancer. 2000;82(1):142–50. 10.1054/bjoc.1999.0891 PubMed DOI PMC

Baquero MT, Hanna JA, Neumeister V, et al. Stathmin expression and its relationship to microtubule-associated protein tau and outcome in breast cancer. Cancer. 2012;118(19):4660–9. 10.1002/cncr.27453 PubMed DOI PMC

He X, Liao Y, Lu W, et al. Elevated STMN1 promotes tumor growth and invasion in endometrial carcinoma. Tumour Biol. 2016;37(7):9951–8. 10.1007/s13277-016-4869-5 PubMed DOI

Reyes HD, Miecznikowski J, Gonzalez-Bosquet J, et al. High stathmin expression is a marker for poor clinical outcome in endometrial cancer: an NRG oncology group/gynecologic oncology group study. Gynecol Oncol. 2017;146(2):247–53. 10.1016/j.ygyno.2017.05.017 PubMed DOI PMC

Price DK, Ball JR, Bahrani-Mostafavi Z, et al. The phosphoprotein Op18/stathmin is differentially expressed in ovarian cancer. Cancer Invest. 2000;18(8):722–30. 10.3109/07357900009012204 PubMed DOI

Němejcová K, Šafanda A, Bártů MK, et al. A comprehensive immunohistochemical analysis of 26 markers in 250 cases of serous ovarian tumors. Diagn Pathol. 2023;18(1):32. 10.1186/s13000-023-01317-9 PubMed DOI PMC

Howitt BE, Nucci MR, Drapkin R, Crum CP, Hirsch MS. Stathmin-1 expression as a complement to p16 helps identify high-grade cervical intraepithelial neoplasia with increased specificity. Am J Surg Pathol. 2013;37(1):89–97. 10.1097/PAS.0b013e3182753f5a PubMed DOI

Lin WC, Chen SC, Hu FC, et al. Expression of stathmin in localized upper urinary tract urothelial carcinoma: correlations with prognosis. Urology. 2009;74(6):1264–9. 10.1016/j.urology.2009.04.088 PubMed DOI

Baldassarre G, Belletti B, Nicoloso MS, et al. p27(Kip1)-stathmin interaction influences sarcoma cell migration and invasion. Cancer Cell. 2005;7(1):51–63. 10.1016/j.ccr.2004.11.025 PubMed DOI

Li X, Wang L, Li T, et al. STMN1 overexpression correlates with biological behavior in human cutaneous squamous cell carcinoma. Pathol Res Pract. 2015;211(11):816–23. 10.1016/j.prp.2015.07.009. 10.1016/j.prp.2015.07.009 PubMed DOI

Ozge Z, Sevil K, Ahmet Y, Hülya A, Sema A. Stathmin 1 and p53 expression in cutaneous squamous cell carcinoma and precursor lesions. Am J Dermatopathol. 2023;45(3):170–5. 10.1097/DAD.0000000000002381 PubMed DOI

Dundr P, Simon K, Němejcová K, et al. Stathmin is a potential therapeutic target but not a prognostic marker in melanoma: an immunohistochemical study of 323 melanocytic lesions. Melanoma Res. 2019;29(2):157–62. 10.1097/CMR.0000000000000550 PubMed DOI

Biaoxue R, Hua L, Wenlong G, Shuanying Y. Overexpression of stathmin promotes metastasis and growth of malignant solid tumors: a systemic review and meta-analysis. Oncotarget. 2016;7(48):78994–9007. 10.18632/oncotarget.12982 PubMed DOI PMC

Biaoxue R, Xiguang C, Hua L, Shuanying Y. Stathmin-dependent molecular targeting therapy for malignant tumor: the latest 5 years’ discoveries and developments. J Transl Med. 2016;14(1):279. 10.1186/s12967-016-1000-z PubMed DOI PMC

WHO Classification of Tumours Editorial Board. Female Genital Tumours. 5th ed. Lyon, France: International Agency for Research on Cancer (IARC). 2020. WHO Classification of Tumours; vol. 4.

Schweppe KW, Beller FK. Clinical data of granulosa cell tumors. J Cancer Res Clin Oncol. 1982;104(1–2):161–9. 10.1007/BF00402064 PubMed DOI

Babarović E, Franin I, Klarić M, et al. Adult Granulosa Cell tumors of the Ovary: a retrospective study of 36 FIGO Stage I cases with emphasis on Prognostic Pathohistological features. Anal Cell Pathol (Amst). 2018;2018:9148124. PubMed PMC

Färkkilä A, Haltia UM, Tapper J, McConechy MK, Huntsman DG, Heikinheimo M. Pathogenesis and treatment of adult-type granulosa cell tumor of the ovary. Ann Med. 2017;49(5):435–47. 10.1080/07853890.2017.1294760 PubMed DOI

McConechy MK, Färkkilä A, Horlings HM, et al. Molecularly defined adult Granulosa Cell Tumor of the Ovary: the clinical phenotype. J Natl Cancer Inst. 2016;108(11):djw134. 10.1093/jnci/djw134 PubMed DOI PMC

Shah SP, Köbel M, Senz J, et al. Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med. 2009;360(26):2719–29. 10.1056/NEJMoa0902542 PubMed DOI

Karnezis AN, Wang Y, Keul J, et al. DICER1 and FOXL2 mutation status correlates with clinicopathologic features in ovarian sertoli-leydig cell tumors. Am J Surg Pathol. 2019;43(5):628–38. 10.1097/PAS.0000000000001232 PubMed DOI

Hanley KZ, Mosunjac MB. Practical review of ovarian sex cord-stromal tumors. Surg Pathol Clin. 2019;12(2):587–620. 10.1016/j.path.2019.02.005 PubMed DOI

Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003;21(20):3798–807. 10.1200/JCO.2003.11.069 PubMed DOI

Wei CH, Fadare O. Ovarian steroid cell tumors: what do we know so far? Front Oncol. 2024;14:1331903. 10.3389/fonc.2024.1331903 PubMed DOI PMC

Burandt E, Young RH. Thecoma of the ovary: a report of 70 cases emphasizing aspects of its histopathology different from those often portrayed and its differential diagnosis. Am J Surg Pathol. 2014;38(8):1023–32. 10.1097/PAS.0000000000000252 PubMed DOI

Lu Y, Liu C, Cheng H, et al. Stathmin, interacting with Nf-κB, promotes tumor growth and predicts poor prognosis of pancreatic cancer. Curr Mol Med. 2014;14(3):328–39. 10.2174/1566524014666140228120913 PubMed DOI

Sun R, Liu Z, Wang L, et al. Overexpression of stathmin is resistant to paclitaxel treatment in patients with non-small cell lung cancer. Tumour Biol. 2015;36(9):7195–204. 10.1007/s13277-015-3361-y PubMed DOI

Werner HM, Trovik J, Halle MK, et al. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer. PLoS ONE. 2014;9(2):e90141. Published 2014 Feb 25. 10.1371/journal.pone.0090141 PubMed DOI PMC

Ray-Coquard I, Morice P, Lorusso D, et al. Non-epithelial ovarian cancer: ESMO Clinical Practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv1–18. 10.1093/annonc/mdy001 PubMed DOI

Brink GJ, Groeneweg JW, Hooft L, Zweemer RP, Witteveen PO. Response to systemic therapies in ovarian adult Granulosa Cell tumors: a Literature Review. Cancers (Basel). 2022;14(12):2998. 10.3390/cancers14122998 PubMed DOI PMC