High-incidence of PTEN mutations in Chinese patients with primary small cell carcinoma of the esophagus

BMC Cancer

Zhimin Zhang²  Hualiang Xiao¹  Fei Xie³  Hui Zhang³  Chuan Chen³  He Xiao³  Zhenzhou Yang³  Dong Wang³  Zengpeng Li¹  Ge Wang³ 

[1] Department of pathology, Daping Hospital, Third Military Medical University, Chongqing 400042, China

[2] Department of Oncology, Wuhan General Hospital of Guangzhou Command, People’s Liberation Army, Wuhan, Hubei 430070, China

[3] Cancer Center, Institute of Surgical Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China

关键词: Mutation;    PIK3CA;    KRAS;    EGFR;    PTEN;    Primary small cell carcinoma of the esophagus;   

Others  :  859148
DOI  :  10.1186/1471-2407-14-19

 received in 2013-07-11, accepted in 2014-01-06,  发布年份 2014

【 摘 要 】

Background

Primary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive tumor with poor prognosis. The aim of this study was to investigate the existence of EGFR, KRAS, PIK3CA and PTEN mutations in PSCCE.

Methods

Clinical–pathological data and paraffin-embedded specimens were collected from 38 patients. Exons 18 to 21 of EGFR, KRAS and PIK3CA status were analyzed by real-time PCR based on ARMS and Scorpion technology in all patients, and the PTEN gene was also screened using real-time PCR and high-resolution melting curve analysis (HRMA).

Results

Only 1 (2.63%) out of 38 patients had EGFR mutations in L858R missense, and KRAS and PIK3CA were not found in the mutational spot in all patients. However, PTEN mutations presented in 14 (36.84%) out of 38 patients, including exon 5 coding for PTEN missense mutation (n =4, 10.53%), exon 6 (n =7, 18.42%), concurrent exon 5 and exon 6 (n =2, 5.26%), and exon 8 (n =1, 2.63%). Concurrent mutations of these genes were not detected in all samples. No statistically significant associations were found between the clinicopathological features and the mutation status of PTEN.

Conclusions

The incidence of PTEN mutations in Chinese patients with PSCCE was higher than that of previous reports in other histological subtypes of esophageal cancer.

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Pantvaidya GH, Pramesh CS, Deshpande MS, Jambhekar NA, Sharma S, Deshpande RK: Small cell carcinoma of the esophagus: the Tata Memorial Hospital experience. Ann Thorac Surg 2002, 74(6):1924-1927.
• [2]Yekeler E, Koca T, Vural S: A rare cause of the cough: primary small cell carcinoma of esophagus-case report. Case Rep Med 2012, 2012:870783.
• [3]Sun KL, He J, Cheng GY, Chai LX: Management of primary small cell carcinoma of the esophagus. Chin Med J (Engl) 2007, 120(5):355-358.
• [4]Kwak EL, Jankowski J, Thayer SP, Lauwers GY, Brannigan BW, Harris PL, Okimoto RA, Haserlat SM, Driscoll DR, Ferry D, Muir B, Settleman J, Fuchs CS, Kulke MH, Ryan DP, Clark JW, Sgroi DC, Haber DA, Bell DW: Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 2006, 12(14 Pt1):4283-4287.
• [5]Sudo T, Mimori K, Nagahara H, Utsunomiya T, Fujita H, Tanaka Y, Shirouzu K, Inoue H, Mori M: Identification of EGFR mutations in esophageal cancer. Eur J Surg Oncol 2007, 33(1):44-48.
• [6]Guo M, Liu S, Lu F: Gefitinib-sensitizing mutations in esophageal carcinoma. N Engl J Med 2006, 354:2193-2194.
• [7]Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, Meijer GA, Vervenne WL, Richel DJ, Van Groeningen C, Giaccone G: Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol 2006, 24:1612-1619.
• [8]Ferry DR, Anderson M, Beddard K, Tomlinson S, Atherfold P, Obszynska J, Harrison R, Jankowski J: A phase II study of Gefitinib Monotherapy in advanced esophageal adenocarcinoma: evidence of gene expression, cellular, and clinical response. Clin Cancer Res 2007, 13(19):5869-5875.
• [9]Puhringer-Oppermann FA, Stein HJ, Sarbia M: Lack of EGFR gene mutations in exons 19 and 21 in esophageal (Barrett’s) adenocarcinomas. Dis Esophagus 2007, 20:9-11.
• [10]Wang WP, Wang KN, Gao Q, Chen LQ: Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction. World J Surg Oncol 2012, 17:10-14.
• [11]Liu QW, Fu JH, Luo KJ, Yang HX, Wang JY, Hu Y, Yang H, Bella E: Identification of EGFR and KRAS mutations in Chinese patients with esophageal squamous cell carcinoma. Dis Esophagus 2011, 24:374-380.
• [12]Kaneko K, Kumekawa Y, Makino R, Nozawa H, Hirayama Y, Kogo M, Konishi K, Katagiri A, Kubota Y, Muramoto T, Kushima M, Ohmori T, Oyama T, Kagawa N, Ohtsu A, Imawari M: EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma. Front Biosci 2010, 15:65-72.
• [13]Sunpaweravong P, Suwiwat S, Sunpaweravong S, Puttawibul P, Mitarnun W: Correlation of epidermal growth factor receptor mutation, immunohistochemistry, and fluorescence in situ hybridization in esophageal squamous cell carcinoma. J Med Assoc Thai 2009, 92(9):1136-1142.
• [14]Mir MM, Dar NA, Salam I, Shah ZA: Mutations in epidermal growth factor receptor gene in esophageal squamous cell carcinoma patients in Kashmir- a high incidence area of India. Int J Health Sci 2008, 2(2):17-25.
• [15]Hanawa M, Suzuki S, Dobashi Y, Yamane T, Kono K, Enomoto N, Ooi A: EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus. Int J Cancer 2006, 118:1173-1180.
• [16]Ohashi K, Sequist LV, Arcila ME, Moran T, Chmielecki J, Lin YL, Pan Y, Wang L, de Stanchina E, Shien K, Aoe K, Toyooka S, Kiura K, Fernandez-Cuesta L, Fidias P, Yang JC, Miller VA, Riely GJ, Kris MG, Engelman JA, Vnencak-Jones CL, Dias-Santagata D, Ladanyi M, Pao W: Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proc Natl Acad Sci U S A 2012, 109(31):E2127-E2133.
• [17]Radojicic J, Zaravinos A, Spandidos DA: HPV, KRAS mutations, alcohol consumption and tobacco smoking effects on esophageal squamous-cell carcinoma carcinogenesis. Int J Biol Markers 2012, 27(1):1-12.
• [18]Lyronis ID, Baritaki S, Bizakis I, Krambovitis E, Spandidos DA: K-ras mutation, HPV infection and smoking or alcohol abuse positively correlate with esophageal squamous carcinoma. Pathol Oncol Res 2008, 14:267-273.
• [19]Marx AH, Zielinski M, Kowitz CM, Dancau AM, Thieltges S, Simon R, Choschzick M, Yekebas E, Kaifi JT, Mirlacher M, Atanackovic D, Brümmendorf TH, Fiedler W, Bokemeyer C, Izbicki JR, Sauter G: Homogeneous EGFR amplification defines a subset of aggressive Barrett’s adenocarcinomas with poor prognosis. Histopathology 2010, 57(3):418-426.
• [20]Tasioudi KE, Saetta AA, Sakellariou S, Levidou G, Michalopoulos NV, Theodorou D, Patsouris E, Korkolopoulou P: pERK activation in esophageal carcinomas: clinicopathological associations. Pathol Res Pract 2012, 208(7):398-404.
• [21]Lord RV, O’Grady R, Sheehan C, Field AF, Ward RL: K-ras codon 12 mutations in Barrett’s oesophagus and adenocarcinomas of the oesophagus and oesophagogastric junction. J Gastroenterol Hepatol 2000, 15:730-736.
• [22]Akagi I, Miyashita M, Makino H, Nomura T, Hagiwara N, Takahashi K, Cho K, Mishima T, Ishibashi O, Ushijima T, Takizawa T, Tajiri T: Overexpression of PIK3CA is associated with lymph node metastasis in esophageal squamous cell carcinoma. Int J Oncol 2009, 34(3):767-775.
• [23]Maeng CH, Lee J, van Hummelen P, Park SH, Palescandolo E, Jang J, Park HY, Kang SY, MacConaill L, Kim KM, Shim YM: High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide- 3-kinase and BRAF mutations. PLoS One 2012, 7(8):e41655.
• [24]Phillips WA, Russell SE, Ciavarella ML, Choong DY, Montgomery KG, Smith K, Pearson RB, Thomas RJ, Campbell IG: Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett’s esophagus. Int J Cancer 2006, 118(10):2644-2646.
• [25]Mori R, Ishiguro H, Kimura M, Mitsui A, Sasaki H, Tomoda K, Mori Y, Ogawa R, Katada T, Kawano O, Harada K, Fujii Y, Kuwabara Y: PIK3CA mutation status in Japanese esophageal squamous cell carcinoma. J Surg Res 2008, 145(2):320-326.
• [26]Hou GQ, Lu ZM, Liu MY, Liu HM, Xue LX: Mutational analysis of the PTEN gene and its effects in esophageal squamous cell carcinoma. Dig Dis Sci 2011, 56(5):1315-1322.
• [27]Ma J, Zhang J, Ning T, Chen Z, Xu C: Association of genetic polymorphisms in MDM2, PTEN and P53 with risk of esophageal squamous cell carcinoma. J Hum Genet 2012, 57(4):261-264.
• [28]Hu YC, Lam KY, Tang JC, Srivastava G: Mutational analysis of the PTEN/MMAC1 gene in primary oesophageal squamous cell carcinomas. Mol Pathol 1999, 52(6):353-356.
• [29]Kato H, Arao T, Matsumoto K, Fujita Y, Kimura H, Hayashi H, Nishiki K, Iwama M, Shiraishi O, Yasuda A, Shinkai M, Imano M, Imamoto H, Yasuda T, Okuno K, Shiozaki H, Nishio K: Gene amplification of EGFR, HER2, FGFR2 and MET in esophageal squamous cell carcinoma. Int J Oncol 2013, 42(4):1151-1158.