TFF3 Expression as Stratification Marker in Borderline Epithelial Tumors of the Ovary
- 129 Downloads
Borderline tumors (BOT) of the ovary account for 10% to 20% of ovarian neoplasms. Like ovarian cancer, BOT encompass several different histological subtypes (serous, mucinous, endometrioid, clear cell, transitional cell and mixed) with serous (SBOT) and mucinous (MBOT) the most common. Current hypotheses suggest low-grade serous carcinoma may develop in a stepwise fashion from SBOT whereas the majority of high grade serous carcinomas develop rapidly presumably from inclusion cysts or ovarian surface epithelium. The pathogenesis of mucinous ovarian tumors is still puzzling. Molecular markers could help to better define relationships between such entities. Trefoil factor-3 (TFF3) is an estrogen-regulated gene associated with prognosis in different types of cancer. It has also been included in a recent marker panel predicting subtypes of ovarian carcinoma. We analyzed the expression of TFF3 by immunohistochemistry in a cohort of 137 BOT and its association with histopathological features. Overall expression rate of TFF3 was 21.9%. None of the BOT with serous and endometrioid histology displayed strong TFF3 expression. On the other hand, TFF3 was highly expressed in 61.4% of MBOT cases and 33.3% of BOT with mixed histology (P < 0.001) suggesting a potential function of the protein in that subtypes. Associations of TFF3 expression with FIGO stage and micropapillary pattern were significant in the overall cohort but confounded by their correlation with histological subtypes. The highly specific expression of TFF3 in MBOT may help to further clarify potential relationships of tumors with mucinous histology and warrants further studies.
KeywordsOvarian cancer Borderline tumors Histological subtypes Prognosis
We thank Katerina Brinkmann and Samira Adel for expert technical assistance. Furthermore, the authors thank Prof. Dr. M.-L. Hansmann, Senckenberg Institute of Pathology, University of Frankfurt, for providing formalin-fixed, paraffin-embedded tissue samples. This work was supported by grants from the Margarete Bonifer-Stiftung, Bad Soden, the H.W. & J. Hector-Stiftung, Mannheim (grant number: M67), and the BANSS-Stiftung, Biedenkopf.
Compliance with Ethical Standards
Conflict of Interest
The authors have declared no conflicts of interest.
- 5.du Bois A, Ewald-Riegler N, de Gregorio N, Reuss A, Mahner S, Fotopoulou C, Kommoss F, Schmalfeldt B, Hilpert F, Fehm T, Burges A, Meier W, Hillemanns P, Hanker L, Hasenburg A, Strauss HG, Hellriegel M, Wimberger P, Keyver-Paik MD, Baumann K, Canzler U, Wollschlaeger K, Forner D, Pfisterer J, Schroder W, Munstedt K, Richter B, Kommoss S, Hauptmann S, Arbeitsgmeinschaft Gynakologische Onkologie Study G (2013) Borderline tumours of the ovary: a cohort study of the Arbeitsgmeinschaft Gynakologische Onkologie (AGO) study group. Eur J Cancer 49(8):1905–1914. doi: 10.1016/j.ejca.2013.01.035 CrossRefPubMedGoogle Scholar
- 7.Lenhard MS, Mitterer S, Kumper C, Stieber P, Mayr D, Ditsch N, Friese K, Burges A (2009) Long-term follow-up after ovarian borderline tumor: relapse and survival in a large patient cohort. Eur J Obstet Gynecol Reprod Biol 145(2):189–194. doi: 10.1016/j.ejogrb.2009.04.031 CrossRefPubMedGoogle Scholar
- 15.Ortiz BH, Ailawadi M, Colitti C, Muto MG, Deavers M, Silva EG, Berkowitz RS, Mok SC, Gershenson DM (2001) Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors. Cancer Res 61(19):7264–7267PubMedGoogle Scholar
- 20.Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, Scurry JP, Scolyer RA, Smith AN, Bali A, Vanden Bergh P, Baron-Hay S, Scott C, Fink D, Hacker NF, Sutherland RL, O'Brien PM (2006) A distinct molecular profile associated with mucinous epithelial ovarian cancer. Br J Cancer 94(6):904–913. doi: 10.1038/sj.bjc.6603003 CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Ahmed ARH, Griffiths AB, Tilby MT, Westley BR, May FEB (2012) TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease. Am J Pathol 180(3):904–916. doi: 10.1016/j.ajpath.2011.11.022 CrossRefPubMedGoogle Scholar
- 30.Kurman RJ, Carcangiu, M.L., Herrington, C.S., Young, R.H (2014) WHO classification of tumours of female reproductive organs. 4th ed. Lyon: International Agency for Research on Cancer, vol 6.Google Scholar
- 35.Nowak M, Merz C, von Maessenhausen A, Vogel W, Boehm D, Svensson M, Carlsson J, Andren O, Perner S (2015) Role of trefoil factor-3 peptide (TFF3) in prostate cancer progression. Lab invest 95:248a-248aGoogle Scholar