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Study of MYB-NFIB chimeric gene expression, tumor angiogenesis, and proliferation in adenoid cystic carcinoma of salivary gland

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Abstract

Adenoid cystic carcinoma (ACC) is one of the common malignant tumors in salivary glands, and the clinical prognosis is poor with frequent distant metastasis which may lead to death. Expression of the MYB-NFIB chimeric gene in ACC has been reported recently. MYB is an oncogene with transcription regulating functions, and NFIB encodes nuclear transcription factor although detailed functions are unknown. This study investigated whether MYB-NFIB chimeric gene expression affects tumor angiogenesis and proliferation in salivary gland ACC. In 26 salivary gland ACC cases, MYB-NFIB chimeric gene expression was analyzed by RT-PCR and direct sequencing. Immunohistochemical studies for CD31, vascular endothelial growth factor (VEGF) and Ki-67 were performed. Tumor angiogenesis was evaluated by blood vessel (CD31-positive) density and tumor proliferation by Ki-67 labeling index, and the relationship with MYB-NFIB chimeric gene expression was analyzed. MYB-NFIB chimeric gene expression was detected in nine of 26 ACC cases. Blood vessel density was significantly higher in chimeric gene-expressing cases compared to non-expressing cases. VEGF score tended to be higher in chimeric gene-expressing cases than in non-expressing cases, while Ki-67 labeling index was not significantly different. The number of chimeric gene-expressing cases increased with age, peaking in the sixties age group and declining thereafter, while the number of non-expressing cases increased with age continuously. In ACC, blood vessel density was significantly higher in MYB-NFIB chimeric gene-expressing cases compared to non-expressing cases, which may be due to higher VEGF production capability. MYB-NFIB chimeric gene expression may also be related to the onset age of ACC.

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References

  1. Fonseca FP, Carvalho MV, Almeida OP, Rangel AL, Takizawa MC, Bueno AG, Vargas PA. Clinicopathologic analysis of 493 cases of salivary gland tumors in a Southern Brazilian population. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114:230–9.

    Article  PubMed  Google Scholar 

  2. Gao M, Hao Y, Huang MX, Ma DQ, Luo HY, Gao Y, Peng X, Yu GY. Clinicopathological study of distant metastases of salivary adenoid cystic carcinoma. Int J Oral Maxillofac Surg. 2013;42:923–8.

    Article  PubMed  Google Scholar 

  3. Weert SV, Bloemena E, Waal IVD, de Bree R, Rietveld DH, Kuik JD, Leemans CR. Adenoid cystic carcinoma of the head and neck: a single-center analysis of 105 consecutive cases over a 30-year period. Oral Oncol. 2013;49:824–9.

    Article  PubMed  Google Scholar 

  4. Perzin KH, Gullane P, Clairmont AC. Adenoid cystic carcinomas arising in salivary glands: a correlation of histologic features and clinical course. Cancer. 1978;42:265–82.

    Article  PubMed  Google Scholar 

  5. Stenmam G, Licitra L, Said-Al-Naief N, et al. Adenoid cystic carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, et al., editors. World Health Organization classification of tumours: WHO classification of head and neck tumours. Lyon: IARC Press; 2017. p. 164–5.

    Google Scholar 

  6. Moskaluk CA. Adenoid cystic carcinoma: clinical and molecular features. Head Neck Pathol. 2013;7:17–22.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Persson M, Andrén Y, Mark J, Horlings HM, Persson F, Stenman G. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA. 2009;106:18740–4.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Stenman G, Andersson MK, Andrén Y. New tricks from an old oncogene: gene fusion and copy number alterations of MYB in human cancer. Cell Cycle. 2010;9:2986–95.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ramsay RG, Gonda TJ. MYB function in normal and cancer cells. Nat Rev Cancer. 2008;8:523–34.

    Article  PubMed  Google Scholar 

  10. Qian F, Kruse U, Lichter P, Sippel AE. Chromosomal localization of the four genes (NFIA, B, C, and X) for the human transcription factor nuclear factor I by FISH. Genomics. 1995;28:66–73.

    Article  PubMed  Google Scholar 

  11. Murtagh J, Martin F, Gronostajski RM. The nuclear factor I (NFI) gene family in mammary gland development and function. J Mammary Gland Biol Neoplasia. 2003;8:241–54.

    Article  PubMed  Google Scholar 

  12. Brill LB II, Kanner WA, Fehr A, Andrén Y, Moskaluk CA, Löning T, Stenman G, Frierson HF Jr. Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 2011;24:1169–76.

    Article  PubMed  Google Scholar 

  13. North JP, McCalmont TH, Fehr A, van Zante A, Stenman G, LeBoit PE. Detection of MYB Alterations and other immunohistochemical markers in primary cutaneous adenoid cystic carcinoma. Am J Surg Pathol. 2015;39:1347–56.

    Article  PubMed  Google Scholar 

  14. Mitani Y, Li J, Rao PH, Zhao YJ, Bell D, Lippman SM, Weber RS, Caulin C, El-Naggar AK. Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: incidence, variability, and clinicopathologic significance. Clin Cancer Res. 2010;16:4722–31.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mitani Y, Rao PH, Futreal PA, Roberts DB, Stephens PJ, Zhao YJ, Zhang L, Mitani M, Weber RS, Lippman SM, Caulin C, El-Naggar AK. Novel chromosomal rearrangements and breakpoints at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome. Clin Cancer Res. 2011;17:7003–14.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rettig EM, Tan M, Ling S, Yonescu R, Bishop JA, Fakhry C, Ha PK. MYB rearrangement and clinicopathologic characteristics in head and neck adenoid cystic carcinoma. Laryngoscope. 2015;125:292–9.

    Article  Google Scholar 

  17. West RB, Kong C, Clarke N, Gilks T, Lipsick JS, Cao H, Kwok S, Montgomery KD, Varma S, Le QT. MYB expression and translocation in adenoid cystic carcinomas and other salivary gland tumors with clinicopathologic correlation. Am J Surg Pathol. 2011;35:92–9.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Fehr A, Kovács A, Löning T, Frierson HF Jr, van den Oord J, Stenman G. The MYB-NFIB gene fusion–a novel genetic link between adenoid cystic carcinoma and dermal cylindroma. J Pathol. 2011;224:322–7.

    Article  PubMed  Google Scholar 

  19. Nakayama T, Miyabe S, Okabe M, Sakuma H, Ijichi K, Hasegawa Y, Nagatsuka H, Shimozato K, Inagaki H. Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma. Mod Pathol. 2009;22:1575–81.

    Article  PubMed  Google Scholar 

  20. Moghadam SA, Abadi AM, Mokhtari S. Immunohistochemical analysis of CD34 expression in salivary gland tumors. J Oral Maxillofac Pathol. 2015;19:30–3.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Faur AC, Lazar E, Cornianu M. Vascular endothelial growth factor (VEGF) expression and microvascular density in salivary gland tumours. APMIS. 2014;122:418–26.

    Article  PubMed  Google Scholar 

  22. Park S, Nam SJ, Keam B, Kim TM, Jeon YK, Lee SH, Hah JH, Kwon TK, Kim DW, Sung MW, Heo DS, Bang YJ. VEGF and Ki-67 overexpression in predicting poor overall survival in adenoid cystic carcinoma. Cancer Res Treat. 2016;48:518–26.

    Article  PubMed  Google Scholar 

  23. Okada Y. Relationships of cervical lymph node metastasis to histopathological malignancy grade, tumor angiogenesis, and lymphatic invasion in tongue cancer. Odontology. 2010;98:153–9.

    Article  PubMed  Google Scholar 

  24. Mohtasham N, Babakoohi S, Shiva A, Shadman A, Kamyab-Hesari K, Shakeri MT, Sharifi-Sistani N. Immunohistochemical study of p53, Ki-67, MMP-2 and MMP-9 expression at invasive front of squamous cell and verrucous carcinoma in oral cavity. Pathol Res Pract. 2013;209:110–4.

    Article  PubMed  Google Scholar 

  25. Stárek I, Salzman R, Kučerová L, Skálová A, Hauer L. Expression of VEGF-C/-D and lymphangiogenesis in salivary adenoid cystic carcinoma. Pathol Res Pract. 2015;211:759–65.

    Article  PubMed  Google Scholar 

  26. Moriyama M, Kumagai S, Kawashiri S, Kojima K, Kakihara K, Yamamoto E. Immunohistochemical study of tumour angiogenesis in oral squamous cell carcinoma. Oral Oncol. 1997;33:369–74.

    Article  PubMed  Google Scholar 

  27. Lim JJ, Kang S, Lee MR, Pai HK, Yoon HJ, Lee JI, Hong SP, Lim CY. Expression of vascular endothelial growth factor in salivary gland carcinomas and its relation to p53, Ki-67 and prognosis. J Oral Pathol Med. 2003;32:552–61.

    PubMed  Google Scholar 

  28. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.

    Article  PubMed  Google Scholar 

  29. Oh IH, Reddy EP. The myb gene family in cell growth, differentiation and apoptosis. Oncogene. 1999;18:3017–33.

    Article  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Ms. Michiko Moride and all members of the Department of Pathology, The Nippon Dental University School of Life Dentistry at Niigata, for advice and technical guidance.

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Authors and Affiliations

  1. Field of Oral and Maxillofacial Imaging and Histopathological Diagnostics, Histopathology of Pathogenic Mechanisms, Course of Applied Science, The Nippon Dental University Graduate School of Life Dentistry at Niigata, 1-8 Hamaura-cho, Chuo-ku, Niigata, Niigata, 951-8580, Japan

    Junya Ono & Yasuo Okada

  2. Department of Pathology, The Nippon Dental University School of Life Dentistry at Niigata, 1-8 Hamaura-cho, Chuo-ku, Niigata, Niigata, 951-8580, Japan

    Yasuo Okada

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  1. Junya Ono
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Correspondence to Junya Ono.

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Ono, J., Okada, Y. Study of MYB-NFIB chimeric gene expression, tumor angiogenesis, and proliferation in adenoid cystic carcinoma of salivary gland. Odontology 106, 238–244 (2018). https://doi.org/10.1007/s10266-017-0326-1

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  • DOI: https://doi.org/10.1007/s10266-017-0326-1

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