Top

Diagnostic Pathology

Published in:

Open Access 01-12-2015 | Short report

Molecular genetic studies on EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 in primary pulmonary adenoid cystic carcinoma

Authors: Zhen Huo, Huanwen Wu, Shanqing Li, Zhiyong Liang

Published in: Diagnostic Pathology | Issue 1/2015

Abstract

Background

Pulmonary adenoid cystic carcinoma (PACC) is an uncommon neoplasm of the lung but represents the predominant type of salivary gland-type lung carcinoma. Only a few studies have focused on the genetic events associated with PACC. The aim of this study was to characterize the genetic events associated with PACC.

Findings

We reviewed 24 cases of primary PACC between 2000 and 2014, including 21 cases reported in our previous study and three new cases added in 2014. Mutation profiling of the EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 genes was performed using next-generation sequencing, Sanger sequencing, and quantitative polymerase chain reaction in 9 successfully amplified cases. The 24 cases of PACC included 7 men and 17 women, aged 24–74 years (mean, 50.8 years). All the cases were located in the trachea or bronchus. No mutations were detected in any of the seven genes in the nine cases that qualified for mutation analysis, and the results using different methods were consistent.

Conclusions

The data presented in this work suggest that EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 may not be driver genes in primary pulmonary adenoid cystic carcinoma.

Yousem SA, Nicholson AG. Adenoid cystic carcinoma. In: Travis WD, Brambilla E, Muller-Hermlink H, Harris C, editors. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004. p. 63–4.

Cheng L, Alexander RE, Maclennan GT, Cummings OW, Montironi R, Lopez-Beltran A, et al. Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol. 2012;25:347–69.CrossRefPubMed

Kim HS, Mitsudomi T, Soo RA, Cho BC. Personalized therapy on the horizon for squamous cell carcinoma of the lung. Lung Cancer. 2013;80:249–55.CrossRefPubMed

Stenman G, Persson F, Andersson MK. Diagnostic and therapeutic implications of new molecular biomarkers in salivary gland cancers. Oral Oncol. 2014;50:683–90.CrossRefPubMed

Cros J, Sbidian E, Hans S, Roussel H, Scotte F, Tartour E, et al. Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours. Ann Oncol. 2013;24:2624–9.CrossRefPubMed

Clauditz TS, Reiff M, Gravert L, Gnoss A, Tsourlakis MC, Munmcher A, et al. Human epidermal growth factor receptor 2 (HER2) in salivary gland carcinomas. Pathology. 2011;43:459–64.CrossRefPubMed

Dahse R, Driemel O, Schwarz S, Kromeyer-Hauschild K, Berndt A, Kosmehl H. KRAS status and epidermal growth factor receptor expression as determinants for anti-EGFR therapies in salivary gland carcinomas. Oral Oncol. 2009;45:826–9.CrossRefPubMed

Vranić S, Bilalović N, Lee LM, Kruslin B, Lilleberg SL, Gatalica Z. PIK3CA and PTEN mutations in adenoid cystic carcinoma of the breast metastatic to kidney. Hum Pathol. 2007;38:1425–31.CrossRefPubMed

Dahse R, Kosmehl H. Detection of drug-sensitizing EGFR exon 19 deletion mutations in salivary gland carcinoma. Br J Cancer. 2008; 99: 90-2.

10.

Wetterskog D, Wilkerson PM, Rodrigues DN, Lambros MB, Fritchie K, Andersson MK, et al. Mutation profiling of adenoid cystic carcinomas from multiple anatomical sitesidentifies mutations in the RAS pathway, but no KIT mutations. Histopathology. 2013;62:543–50.CrossRefPubMed

11.

Sequeiros-Santiago G, Garcia-Carracedo D, Fresno MF, Suarez C, Rodrigo JP, Gonzalez MV. Oncogene amplification pattern in adenoid cystic carcinoma of the salivary glands. Oncol Rep. 2009;21:1215–22.PubMed

12.

Bell D, Sniegowski M, Wani K, Prieto V, Esmaeli B. Mutational landscape of lacrimal gland carcinomas and implications for treatment. Head Neck. 2015. [Epub ahead of print]

13.

Tetsu O, Phuchareon J, Chou A, Cox DP, Eisele DW, Jordan RC. Mutations in the c-Kit gene disrupt mitogen-activated protein kinase signaling during tumor development in adenoid cystic carcinoma of the salivary glands. Neoplasia. 2010;12:708–17.CrossRefPubMedCentralPubMed

14.

Dahse R, Driemel O, Schwarz S, Dahse J, Kromeyer-Hauschild K, Berndt A, et al. Epidermal growth factor receptor kinase domain mutations are rare in salivary gland carcinomas. Br J Cancer. 2009;100:623–5.CrossRefPubMedCentralPubMed

15.

Ross JS, Wang K, Rand JV, Sheehan CE, Jennings TA, Al-Rohil RN, et al. Comprehensive genomic profiling of relapsed and metastatic adenoid cystic carcinomas by next-generation sequencing reveals potential new routes to targeted therapies. Am J Surg Pathol. 2014;38:235–8.CrossRefPubMed

16.

Stephens PJ, Davies HR, Mitani Y, Van Loo P, Shlien A, Tarpey PS, et al. Whole exome sequencing of adenoid cystic carcinoma. J Clin Invest. 2013;123:2965–8.CrossRefPubMedCentralPubMed

17.

Vidal L, Tsao MS, Pond GR, Cohen EE, Cohen RB, Chen EX, et al. Fluorescence in situ hybridization gene amplification analysis of EGFR and HER2 in patients with malignant salivary gland tumors treated with lapatinib. Head Neck. 2009;31:1006–12.CrossRefPubMedCentralPubMed

18.

Macarenco RS, Uphoff TS, Gilmer HF, Jenkins RB, Thibodeau SN, Lewis JE, et al. Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study. Mod Pathol. 2008;21:1168–75.CrossRefPubMedCentralPubMed

19.

Aubry MC, Heinrich MC, Molina J, Lewis JE, Yang P, Cassivi SD, et al. Primary adenoid cystic carcinoma of the lung: absence of KIT mutations. Cancer. 2007;110:2507–10.CrossRefPubMed

20.

Huo Z, Meng Y, Wu H, Shen J, Bi Y, Luo Y, et al. Adenoid cystic carcinoma of the tracheobronchial tree: clinicopathologic and immunohistochemical studies of cases. Int J Clin Exp Pathol. 2014;7:7527–35.PubMedCentralPubMed

21.

Han SW, Kim HP, Jeon YK, Oh DY, Lee SH, Kim DW, et al. Mucoepidermoid carcinoma of lung: potential target of EGFR-directed treatment. Lung Cancer. 2008;61:30–4.CrossRefPubMed

22.

Yoshida A, Tsuta K, Nakamura H, Kohno T, Takahashi F, Asamura H, et al. Comprehensive histologic analysis of ALK-rearranged lung carcinomas. Am J Surg Pathol. 2011;35:1226–34.CrossRefPubMed

23.

Yau NK, Fong AY, Leung HF, Verhoeft KR, Lim QY, Lam WY, et al. Pan-Cancer Review of ALK mutations: implications for carcinogenesis and therapy. Curr Cancer Drug Targets. 2015;15:327–36.CrossRefPubMed

24.

Bai Y, Kim JY, Watters JM, Fang B, Kinose F, Song L, et al. Adaptive responses to dasatinib-treated lung squamous cell cancer cells harboring DDR2 mutations. Cancer Res. 2014;74:7217–28.CrossRefPubMed

25.

Swanton C, Burrell RA. Advances in personalized therapeutics in non-small cell lung cancer: 4q12 amplification, PDGFRA oncogene addiction and sunitinib sensitivity. Cancer Biol Ther. 2009;8:2051–3.CrossRefPubMed

Title: Molecular genetic studies on EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 in primary pulmonary adenoid cystic carcinoma
Authors: Zhen Huo
Huanwen Wu
Shanqing Li
Zhiyong Liang
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-015-0409-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Molecular genetic studies on EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 in primary pulmonary adenoid cystic carcinoma

Abstract

Background

Findings

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Findings

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

Unusual coexistence of extramedullary plasmacytoma and nasopharyngeal carcinoma in nasopharynx

miR-203 inhibition of renal cancer cell proliferation, migration and invasion by targeting of FGF2

PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway

Detection of KRAS, NRAS and BRAF by mass spectrometry - a sensitive, reliable, fast and cost-effective technique

Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer

Histopathological grading of breast ductal carcinoma In Situ: validation of a web-based survey through intra-observer reproducibility analysis