Mist1: a novel nuclear marker for acinic cell carcinoma of the salivary gland
Muscle, intestine, and stomach expression 1 (Mist1) is a transcription factor that functions in the development of granule organisation in serous exocrine cells of the gastrointestinal tract. The aim of this study was to investigate whether Mist1 can be used as a marker for acinic cell carcinoma (AciCC) of the salivary gland. Immunohistochemistry (IHC) was used to analyse Mist1 expression in AciCC (n = 26), secretory carcinoma (SC; n = 18) and 12 other types of salivary gland tumours (n = 99). Strong Mist1 staining was observed in normal serous acinar cells and plasma cells. Mist1 was diffusely expressed in AciCC, with the immunostaining intensity ranging from moderate (4/26) to strong (22/26). Most SC specimens were either negative (7/18) or focally and mildly positive (9/18) for Mist1. Only two SC cases demonstrated a moderate level of Mist1 staining. When moderate-to-strong Mist1 staining was used as the criterion of positivity, all the tested salivary gland tumours other than AciCC were negative for Mist1, except for two cases of SC. Previously cut tissue sections and decalcified specimens exhibited reduced Mist1 immunostaining intensity, which may give false-negative results. In summary, Mist1 is a sensitive marker for serous acinar cells of salivary glands and AciCC, and background non-tumour acinar cells and plasma cells can serve as good internal positive controls.
KeywordsMist1 BHLHA15 Acinic cell carcinoma Secretory carcinoma Salivary gland
Min-Shu Hsieh, Yi-Hsuan Lee and Yung-Ming Jeng performed the research. Min-Shu Hsieh and Yung-Ming Jeng designed the research study and analysed the data. Min-Shu Hsieh and Yung-Ming Jeng wrote the paper.
This study was supported by grants from the National Taiwan University Hospital (Nos. 106-M3739, 106-003612, 107-N3971, and 107-N4038).
Compliance with ethical standards
This study was approved by the Research Ethics Committee of National Taiwan University Hospital (201504071RINC) and conducted in accordance with the Declaration of Helsinki.
Conflict of interest
The authors declare that they have no conflict of interest.
- 4.Lennerz JK, Kim SH, Oates EL, Huh WJ, Doherty JM, Tian X, Bredemeyer AJ, Goldenring JR, Lauwers GY, Shin YK, Mills JC (2010) The transcription factor MIST1 is a novel human gastric chief cell marker whose expression is lost in metaplasia, dysplasia, and carcinoma. Am J Pathol 177:1514–1533CrossRefGoogle Scholar
- 8.Simpson RHW, Chiosea S, Katabi N, Leivo I, Vielh P, Williams MD (2017) Acinic cell carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Sllotweg PJ (eds) World Health Organization classification of head and neck tumours. IARC Press, Lyon, pp 166–167Google Scholar
- 9.Skalova A, Vanecek T, Martinek P, Weinreb I, Stevens TM, Simpson RHW, Hyrcza M, Rupp NJ, Baneckova M, Michal M Jr, Slouka D, Svoboda T, Metelkova A, Etebarian A, Pavelka J, Potts SJ, Christiansen J, Steiner P, Michal M (2018) Molecular profiling of mammary analog secretory carcinoma revealed a subset of tumors harboring a novel ETV6-RET translocation: report of 10 cases. Am J Surg Pathol 42:234–246CrossRefGoogle Scholar
- 10.Skálová A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, Starek I, Geierova M, Simpson RH, Passador-Santos F, Ryska A, Leivo I, Kinkor Z, Michal M (2010) Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol 34:599–608Google Scholar
- 11.Skálová A, Bell D, Bishop JA, Inagaki H, Seethala R, Vielh P (2017) Secretory carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Sllotweg PJ (eds) World Health Organization classification of head and neck tumours. IARC Press, Lyon, p 177Google Scholar
- 15.Mariano FV, Gómez CA, de Souza do Nascimento J, Dos Santos HT, Egal ES, Montalli VA, Vargas PA, de Almeida OP, Altemani A (2016) Lysozyme expression can be useful to distinguish mammary analog secretory carcinoma from acinic cell carcinoma of salivary glands. Head Neck Pathol 10:429–436CrossRefGoogle Scholar
- 16.Hsieh MS, Jeng YM, Jhuang YL, Chou YH, Lin CY (2016) Carbonic anhydrase VI: a novel marker for salivary serous acinar differentiation and its application to discriminate acinic cell carcinoma from mammary analogue secretory carcinoma of the salivary gland. Histopathology 68:641–647CrossRefGoogle Scholar
- 18.Ruifrok AC, Johnston DA (2001) Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol 23:291–299Google Scholar
- 19.Skálová A, Sima R, Vanecek T, Muller S, Korabecna M, Nemcova J, Elmberger G, Leivo I, Passador-Santos F, Walter J, Rousarova M, Jedlickova K, Curik R, Geierova M, Michal M (2009) Acinic cell carcinoma with high-grade transformation: a report of 9 cases with immunohistochemical study and analysis of TP53 and HER-2/neu genes. Am J Surg Pathol 33:1137–1145CrossRefGoogle Scholar
- 20.Ohtomo R, Mori T, Shibata S, Tsuta K, Maeshima AM, Akazawa C, Watabe Y, Honda K, Yamada T, Yoshimoto S, Asai M, Okano H, Kanai Y, Tsuda H (2013) SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis. Mod Pathol 26:1041–1050CrossRefGoogle Scholar
- 22.Hsieh MS, Lee YH, Chang YL (2016) SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma. Hum Pathol 56:134–142CrossRefGoogle Scholar
- 23.Andreasen S, Varma S, Barasch N, Thompson LDR, Miettinen M, Rooper L, Stelow EB, Agander TK, Seethala RR, Chiosea SI, Homøe P, Wessel I, Larsen SR, Erentaite D, Bishop JA, Ulhøi BP, Kiss K, Melchior LC, Pollack JR, West RB (2019) The HTN3-MSANTD3 fusion gene defines a subset of acinic cell carcinoma of the salivary gland. Am J Surg Pathol 43:489–496CrossRefGoogle Scholar