Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Search articles, authors, keywords, DOl and etc.
Because of the poor prognosis of lacrimal adenoid cystic carcinoma (LACC), we aimed to investigate the effects of perineural invasion (PNI) and consequent aberrations in GDNF/GFRα-1/RET protein expression on LACC recurrence.
Clinicopathological data for 51 histologically confirmed patients with LACC enrolled between 2001 and 2017 were retrospectively analyzed. Hematoxylin and eosin staining was applied to assess PNI. Tissue-based immunohistochemistry (IHC) detection of GDNF, GFRα-1, and RET proteins was performed on LACC formalin-fixed, paraffin-embedded specimens. We generated semi-quantitative data of the IHC results and compared them with the clinicopathological data for the 51 patients.
Of the 51 patients, 19 (37.3%) were PNI positive. Recurrence was more common for LACC with than without PNI (73.7% vs. 37.5%, P = 0.01). GDNF, GFRα-1, and RET proteins were expressed in 62.7%, 62.7%, and 54.9% of the 51 patients with LACC, respectively. The expression of all 3 proteins was more common in patients with than without PNI. In agreement with previous findings, PNI-associated GFRα-1 and RET positivity, as detected by IHC, remained significantly associated with recurrence, whereas GDNF expression, as detected by IHC, was not correlated with LACC recurrence. Specifically, patients with concurrent GFRα-1 and RET expression may have a high risk of PNI (89.5% positivity rate) and recurrence (84.2% positivity rate).
PNI may contribute to LACC recurrence. The concurrent expression of GFRα-1 and RET proteins, as detected by IHC, may potentially be associated with LACC PNI and recurrence.
Barrett AW, Speight PM. Perineural invasion in adenoid cystic carcinoma of the salivary glands: a valid prognostic indicator? Oral Oncol. 2009; 45: 936-40.
Luksic I, Suton P, Macan D, Dinjar K. Intraoral adenoid cystic carcinoma: is the presence of perineural invasion associated with the size of the primary tumour, local extension, surgical margins, distant metastases, and outcome? Br J Oral Maxillofac Surg. 2014; 52: 214-8.
Font RL, Del Valle M, Avedano J, Longo M, Boniuk M. Primary adenoid cystic carcinoma of the conjunctiva arising from the accessory lacrimal glands: a clinicopathologic study of three cases. Cornea. 2008; 27: 494-7.
Ko YH, Lee MA, Hong YS, Lee KS, Jung CK, Kim YS, et al. Prognostic factors affecting the clinical outcome of adenoid cystic carcinoma of the head and neck. Jpn J Clin Oncol. 2007; 37: 805-11.
Coca-Pelaz A, Rodrigo JP, Bradley PJ, Vander Poorten V, Triantafyllou A, Hunt JL, et al. Adenoid cystic carcinoma of the head and neck – an update. Oral Oncol. 2015; 51: 652-61.
Kaur A, Harrigan MR, MeKeever PE, Ross DA. Adenoid cystic carcinoma metastatic to the dura: report of two cases. J Neurooncol. 1999; 44: 267-73.
Khan AJ, DiGiovanna MP, Ross DA, Sasaki CT, Carter D, Son YH, et al. Adenoid cystic carcinoma: a retrospective clinical review. Int J Cancer. 2001; 96: 149-58.
Lin TT, He YJ, Zhang H, Song GX, Tang DR, Zhao HF. Analysis of treatment and prognosis of orbital adenoid cystic carcinoma. Zhonghua Yan Ke Za Zhi. 2009; 45: 309-13.
Amit M, Eran A, Billan S, Fridman E, Na’ara S, Charas T, et al. Perineural spread in noncutaneous head and neck cancer: new insights into an old problem. J Neurol Surg B Skull Base. 2016; 77: 86-95.
Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 1993; 260: 1130-2.
Soler RM, Dolcet X, Encinas M, Egea J, Bayascas JR, Comella JX. Receptors of the glial cell line-derived neurotrophic factor family of neurotrophic factors signal cell survival through the phosphatidylinositol 3-kinase pathway in spinal cord motoneurons. J Neurosci. 1999; 19: 9160-9.
Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, et al. GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family. J Biol Chem. 1997; 272: 33111-7.
Choi YD, Jung JY, Baek M, Khan S, Song PI, Ryu S, et al. APE1 promotes pancreatic cancer proliferation through GFRalpha1/Src/ ERK axis-cascade signaling in response to GDNF. Int J Mol Sci. 2020; 21: 3586.
Wolkow N, Jakobiec FA, Lee H, Sutula FC. Long-term outcomes of globe-preserving surgery with proton beam radiation for adenoid cystic carcinoma of the lacrimal gland. Am J Ophthalmol. 2018; 195: 43-62.
Sanders JC, Mendenhall WM, Werning JW. Adenoid cystic carcinoma of the lacrimal gland. Am J Otolaryngol. 2016; 37: 144-7.
Mihailovic N, Elges S, Glitz B, Merte RL, Alnawaiseh M, Buerke B, et al. Treatment options for adenoid cystic lacrimal gland carcinoma – a case series and literature review. Klin Monbl Augenheilkd. 2019; 236: 35-8.
Hung JY, Wei YH, Huang CH, Chen LW, Fuh CS, Liao SL. Survival outcomes of eye-sparing surgery for adenoid cystic carcinoma of lacrimal gland. Jpn J Ophthalmol. 2019; 63: 344-51.
Lin YH, Huang SM, Yap WK, Yang JW, Yeung L, Tsan DL, et al. Outcomes in patients with lacrimal gland carcinoma treated with definitive radiotherapy or eye-sparing surgery followed by adjuvant radiotherapy. Radiat Oncol. 2020; 15: 156.
Okada Y, Takeyama H, Sato M, Morikawa M, Sobue K, Asai K, et al. Experimental implication of celiac ganglionotropic invasion of pancreatic-cancer cells bearing c-ret proto-oncogene with reference to glial-cell-line-derived neurotrophic factor (GDNF). Int J Cancer. 1999; 81: 67-73.
Wiesenhofer B, Stockhammer G, Kostron H, Maier H, Hinterhuber H, Humpel C. Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GFR-alpha 1) are strongly expressed in human gliomas. Acta Neuropathol. 2000; 99: 131-7.
Funahashi H, Okada Y, Sawai H, Takahashi H, Matsuo Y, Takeyama H, et al. The role of glial cell line-derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells. J Surg Oncol. 2005; 91: 77-83.
Moodley S, Lian EY, Crupi MJF, Hyndman BD, Mulligan LM. RET isoform-specific interaction with scaffold protein Ezrin promotes cell migration and chemotaxis in lung adenocarcinoma. Lung Cancer. 2020; 142: 123-31.
Iwahashi N, Nagasaka T, Tezel G, Iwashita T, Asai N, Murakumo Y, et al. Expression of glial cell line-derived neurotrophic factor correlates with perineural invasion of bile duct carcinoma. Cancer. 2002; 94: 167-74.
Henderson CE, Phillips HS, Pollock RA, Davies AM, Lemeulle C, Armanini M, et al. GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle. Science. 1994; 266: 1062-4.
Kawai K, Takahashi M. Intracellular RET signaling pathways activated by GDNF. Cell Tissue Res. 2020; 382: 113-23.
Zhu S, Li Y, Bennett S, Chen J, Weng IZ, Huang L, et al. The role of glial cell line-derived neurotrophic factor family member artemin in neurological disorders and cancers. Cell Prolif. 2020; 53: e12860.
Terasaki M, Tokutomi T, Maruiwa H, Sugita Y, Harada H, Shigemori M. High-grade adenoid cystic carcinoma originating from the lacrimal gland. Brain Tumor Pathol. 2000; 17: 159-63.
Nagao T, Gaffey TA, Serizawa H, Sugano I, Ishida Y, Yamazaki K, et al. Dedifferentiated adenoid cystic carcinoma: a clinicopathologic study of 6 cases. Mod Pathol. 2003; 16: 1265-72.
Garden AS, Weber RS, Morrison WH, Ang KK, Peters LJ. The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation. Int J Radiat Oncol Biol Phys. 1995; 32: 619-26.
Veit C, Genze F, Menke A, Hoeffert S, Gress TM, Gierschik P, et al. Activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and invasion of pancreatic carcinoma cells. Cancer Res. 2004; 64: 5291-300.
Ito Y, Okada Y, Sato M, Sawai H, Funahashi H, Murase T, et al. Expression of glial cell line-derived neurotrophic factor family members and their receptors in pancreatic cancers. Surgery. 2005; 138: 788-94.
Creative Commons Attribution-NonCommercial 4.0 International License