Abstract
Introduction
Cripto-1 is a member of the epidermal growth factor—Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. Objective: We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands.
Methods
A total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were evaluated semiquantitatively (scores 0–3). For statistical analysis, Mann–Whitney and Kruskal–Wallis tests were performed and a significance level of p ≤ 0.05 was established.
Results
Most CaExPAs (n = 10) were strong positive (score 3) for Cripto-1, and only three cases of PAs and two specimens of NSGs exhibited some expression (score 1), being statistically significant these findings (p < 0.001). No difference between the expression of this protein in tumors of major and minor salivary glands was observed. Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8) when compared to those without capsular invasion (intracapsular pattern) (p = 0.036). Patients with or without lymph node metastasis showed no difference (p = 0.294).
Conclusion
The results revealed a significantly higher expression of Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly deregulated in PA malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior (invasive growth) in salivary gland tumors.
Similar content being viewed by others
References
Mariano FV, Noronha ALF, Gondak RO, Altemani AM, De Almeida OP, Kowalski LP (2013) Carcinoma ex pleomorphic adenoma in a Brazilian population: clinico-pathological analysis of 38 cases. Int J Oral Maxillofac Surg 42:685–692. https://doi.org/10.1016/j.ijom.2013.02.012
Alaizari NA, Tarakji B, Al-Maweri SA, Al-Shamiri HM, Darwish S, Baba F (2015) p53 expression in pleomorphic adenoma of salivary glands: a systematic review and meta-analysis. Arch Oral Biol 60:1437–1441. https://doi.org/10.1016/j.archoralbio.2015.06.019
Silva LP, Santana T, Sedassari BT, de Sousa SM, Sobral APV, Freitas RA et al (2017) Apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in malignant transformation of salivary gland pleomorphic adenoma. Eur Arch Otorhinolaryngol 274:3203–3209. https://doi.org/10.1007/s00405-017-4605-9
Di Palma S (2013) Carcinoma ex pleomorphic adenoma, with particular emphasis on early lesions. Head Neck Pathol 7:68–76. https://doi.org/10.1007/s12105-013-0454-z
Liu Q, Cui X, Yu X, Bian BS, Qian F, Hu XG et al (2017) Cripto-1 acts as a functional marker of cancer stem-like cells and predicts prognosis of the patients in esophageal squamous cell carcinoma. Mol Cancer 16:81. https://doi.org/10.1186/s12943-017-0650-7
Mahmoudian RA, Abbaszadegan MR, Forghanifard MM, Moghbeli M, Moghbeli F, Chamani J et al (2017) Biological and clinicopathological significance of Cripto-1 expression in the progression of human ESCC. Rep Biochem Mol Biol 5:83–90
Skalova A, Hellquist H (2014) Histopathology of the salivary glands. Springer, Berlin
El-Naggar A, Chan JKC, Grandis JR, Takata T, Slootweg PJ (2017) WHO classification of head and neck tumours. IARC Press, Lyon
Yoon HJ, Hong JS, Shin WJ, Lee YJ, Hong KO, Lee JI et al (2011) The role of Cripto-1 in the tumorigenesis and progression of oral squamous cell carcinoma. Oral Oncol 47:1023–1031. https://doi.org/10.1016/j.oraloncology.2011.07.019
Gao M, Hao Y, Huang MX, Ma DQ, Chen Y, Luo HY et al (2017) Salivary gland tumours in a northern Chinese population: a 50-year retrospective study of 7190 cases. Int J Oral Maxillofac Surg 46:343–349. https://doi.org/10.1016/j.ijom.2016.09.021
Wu Z, Li G, Wu L, Weng D, Li X, Yao K (2009) Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma. BMC Cancer 9:315. https://doi.org/10.1186/1471-2407-9-315
Xu CH, Cao L, Wei Y, Yu LK (2015) Serum cripto-1 as a clinical marker for lung cancer. Int J Biol Markers. 30:e369-373. https://doi.org/10.5301/jbm.5000155
Zhang H, Zhang B, Gao L, Zhang L, Zhu K, Cheng R et al (2017) Clinical significance of cripto-1 expression in lung adenocarcinoma. Oncotarget 8:79087–79098. https://doi.org/10.18632/oncotarget.15761
Francescangeli F, Contavalli P, De Angelis ML, Baiocchi M, Gambara G, Pagliuca A et al (2015) Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer. Cell Death Differ 22:1700–1713. https://doi.org/10.1038/cdd.2015.19
Wei B, Jin W, Ruan J, Xu Z, Zhou Y, Liang J et al (2015) Cripto-1 expression and its prognostic value in human bladder cancer patients. Tumour Biol 36:1105–1113. https://doi.org/10.1007/s13277-014-2695-1
Wang JH, Wei W, Xu J, Guo ZX, Xiao CZ, Zhang YF et al (2015) Elevated expression of Cripto-1 correlates with poor prognosis in hepatocellular carcinoma. Oncotarget 6:35116–35128. https://doi.org/10.18632/oncotarget.5057
Castro NP, Fedorova-Abrams ND, Merchant AS, Rangel MC, Nagaoka T, Karasawa H et al (2015) Cripto-1 as a novel therapeutic target for triple negative breast cancer. Oncotarget 6:11910–11929. https://doi.org/10.18632/oncotarget.4182
Ligtenberg MA, Witt K, Galvez-Cancino F, Sette A, Lundqvist A, Lladser A et al (2016) Cripto-1 vaccination elicits protective immunity against metastatic melanoma. Oncoimmunology 5:e1128613. https://doi.org/10.1080/2162402X.2015.1128613
Sun G, Yan SS, Shi L, Wan ZQ, Jiang N, Fu LS et al (2016) MicroRNA-15b suppresses the growth and invasion of glioma cells through targeted inhibition of cripto-1 expression. Mol Med Rep 13:4897–4903. https://doi.org/10.3892/mmr.2016.5126
Huang C, Chen W, Wang X, Zhao J, Li Q, Fu Z (20150 Cripto-1 promotes the epithelial-mesenchymal transition in esophageal squamous cell carcinoma cells. Evid Based Complement Alternat Med. 2015:421285. https://doi.org/10.1155/2015/421285
Liu Y, Qin Z, Yang K, Liu R, Xu Y (2017) Cripto-1 promotes epithelial-mesenchymal transition in prostate cancer via Wnt/β-catenin signaling. Oncol Rep 37:1521–1528. https://doi.org/10.3892/or.2017.5378
Klauzinska M, McCurdy D, Rangel MC, Vaidyanath A, Castro NP, Shen MM et al (2015) Cripto-1 ablation disrupts alveolar development in the mouse mammary gland through a progesterone receptor-mediated pathway. Am J Pathol 185:2907–2922. https://doi.org/10.1016/j.ajpath.2015.07.023
Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S et al (2010) Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci 101:93–299. https://doi.org/10.1111/j.1349-7006.2009.01419.x
Rangel MC, Karasawa H, Castro NP, Nagaoka T, Salomon DS, Bianco C (2012) Role of Cripto-1 during epithelial-to-mesenchymal transition in development and cancer. Am J Pathol 180:2188–2200. https://doi.org/10.1016/j.ajpath.2012.02.031
Acknowledgements
This work was supported by the Brazilian National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES).
Funding
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
All procedures performed in this study involving the patient were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The approval of the local ethics committee is present in the methods section in this article.
Informed consent
Informed consent was obtained from the patients in this study.
Conflict of interest
All authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Silva, L.P., da Silva, L.A.B., Sedassari, B.T. et al. Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland. Eur Arch Otorhinolaryngol 275, 1595–1600 (2018). https://doi.org/10.1007/s00405-018-4960-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00405-018-4960-1