Expression of hypoxia-related markers in inflammatory myofibroblastic tumors of the head and neck

World Journal of Surgical Oncology

Zhong-Jie Lu⁴  Qin-Ying Wang³  Hong-Tian Yao⁵  Shui-Hong Zhou³  Ting-Ting Wu³  Tao Jiang²  Kui-Rong Wang¹ 

[1] Department of Anaesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China;Current address: Department of Otolaryngology, Yinzhou People’s Hospital of Ningbo City, Zhejiang Province, China;Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China;Department of Radiotherapy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China;Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China

关键词: Recurrence;    Prognosis;    PI3K/Akt pathway;    Inflammatory myofibroblastic tumor;    Hypoxia-inducible factor 1α;    Glucose transporter-1;   

Others  :  820901
DOI  :  10.1186/1477-7819-11-294

 received in 2013-06-19, accepted in 2013-11-09,  发布年份 2013

【 摘 要 】

Background

The etiology of inflammatory myofibroblastic tumors (IMTs) is controversial and the prognosis is unpredictable. Previous studies have not investigated the expression of hypoxia-related markers in IMTs.

Methods

Between 2002 and 2012, 12 consecutive patients with histologically proven IMTs were enrolled in the study. Immunohistochemistry was used to detect GLUT-1, HIF-1α, PI3K, and p-Akt expression in paraffin-embedded tumor specimens. Associations among GLUT-1, HIF-1α, PI3K, and p-Akt protein expression and clinical parameters were investigated.

Results

The mean duration of follow-up was 52.1 months (range, 11 to 132 months). Six patients had local recurrence. GLUT-1, HIF-1α, PI3K, and p-Akt expression were detected in 41.7%, 50.0%, 33.3%, and 41.7% of patients, respectively. Fisher’s exact test revealed significant correlations between recurrence of IMT and PI3K expression (P = 0.01) and p-Akt expression (P = 0.015). Univariate analyses revealed significant correlations between survival and GLUT-1 expression (P = 0.028), PI3K expression (P = 0.006), and p-Akt expression (P = 0.028). Multivariate analysis did not show a significant relationship between survival and GLUT-1, HIF-1α, PI3K, or p-Akt. Spearman rank correlation analysis showed significant correlations between HIF-1α and PI3K expression (r = 0.707, P = 0.01) and between p-Akt and PI3K expression (r = 0.837, P = 0.001).

Conclusions

Although our results are inconclusive owing to the small sample size, they suggest that PI3K and p-Akt expression may play a role in the recurrence of IMTs of the head and neck.

【 授权许可】

   
2013 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Fletcher CDM, Unni KK, Mertens F: World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Soft Tissues and Bone. Lyon: IARC Press; 2002:91-93.
• [2]Ong HS, Ji T, Zhang CP, Li J, Wang LZ, Li RR, Sun J, Ma CY: Head and neck inflammatory myofibroblastic tumor (IMT): evaluation of clinicopathologic and prognostic features. Oral Oncol 2012, 48:141-148.
• [3]Jiang YH, Cheng B, Ge MH, Cheng Y, Zhang G: Comparison of the clinical and immunohistochemical features, including anaplastic lymphoma kinase (ALK) and p53, in inflammatory myofibroblastictumours. J Int Med Res 2009, 37:867-877.
• [4]Coffin CM, Hornick JL, Fletcher CD: Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J SurgPathol 2007, 31:509-520.
• [5]Lacoste L, Galant C, Gigot JF, Lacoste B, Annet L: Inflammatory myofibroblastic tumor of the pancreatic head. JBR-BTR 2012, 95:267-269.
• [6]Obrzut SL, Halpern BS, Monchamp T, Grabski K, Watts WJ, Czernin J: The role of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography in monitoring the immunosuppressive therapy response of inflammatory myofibroblastic tumor. Mol Imaging Biol 2004, 6:126-130.
• [7]Han MW, Lee HJ, Cho KJ, Kim JS, Roh JL, Choi SH, Nam SY, Kim SY: Role of FDG-PET as a biological marker for predicting the hypoxic status of tongue cancer. Head Neck 2012, 34:1395-1402.
• [8]Nagamatsu A, Umesaki N, Li L, Tanaka T: Use of 18F-fluorodeoxyglucose positron emission tomography for diagnosis of uterine sarcomas. Oncol Rep 2010, 23:1069-1076.
• [9]Rademakers SE, Lok J, van der Kogel AJ, Bussink J, Kaanders JH: Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4. BMC Cancer 2011, 11:167. BioMed Central Full Text
• [10]Taddei ML, Giannoni E, Comito G, Chiarugi P: Microenvironment and tumor cell plasticity: an easy way out. Cancer Lett 2013, 341:80-96.
• [11]Cannito S, Novo E, Compagnone A, Valfrè Di Bonzo L, Busletta C, Zamara E, Paternostro C, Povero D, Bandino A, Bozzo F, Cravanzola C, Bravoco V, Colombatto S, Parola M: Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells. Carcinogenesis 2008, 29:2267-2278.
• [12]Wu XH, Chen SP, Mao JY, Ji XX, Yao HT, Zhou SH: Expression and significance of hypoxia-inducible factor-1α and glucose transporter-1 in laryngeal carcinoma. OncolLett 2013, 5:261-266.
• [13]André H, Pereira TS: Identification of an alternative mechanism of degradation of the hypoxia-inducible factor-1α. J BiolChem 2008, 283:29375-29384.
• [14]Semenza GL: Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 2010, 29:625-634.
• [15]Zheng Y, Ni Y, Huang X, Wang Z, Han W: Overexpression of HIF-1α indicates a poor prognosis in tongue carcinoma and may be associated with tumour metastasis. OncolLett 2013, 5:1285-1289.
• [16]Ino Y, Yamazaki-Itoh R, Oguro S, Shimada K, Kosuge T, Zavada J, Kanai Y, Hiraoka N: Arginase II expressed in cancer-associated fibroblasts indicates tissue hypoxia and predicts poor outcome in patients with pancreatic cancer. PLoS One 2013, 8:e55146.
• [17]Schwartz DL, Powis G, Thitai-Kumar A, He Y, Bankson J, Williams R, Lemos R, Oh J, Volgin A, Soghomonyan S, Nishii R, Alauddin M, Mukhopadhay U, Peng Z, Bornmann W, Gelovani J: The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Mol Cancer Ther 2009, 8:947-958.
• [18]Zhu H, Feng Y, Zhang J, Zhou X, Hao B, Zhang G, Shi R: Inhibition of hypoxia inducible factor 1α expression suppresses the progression of esophageal squamous cell carcinoma. Cancer BiolTher 2011, 11:981-987.
• [19]Agani F, Jiang BH: Oxygen-independent regulation of HIF-1: novel involvement of PI3K/AKT/mTORpathway in cancer. Curr Cancer Drug Targets 2013, 13:245-251.
• [20]Melstrom LG, Salabat MR, Ding XZ, Milam BM, Strouch M, Pelling JC, Bentrem DJ: Apigenin inhibits the GLUT-1 glucose transporter and the phosphoinositide 3-kinase/Akt pathway in human pancreatic cancer cells. Pancreas 2008, 37:426-431.
• [21]Chen YF, Zhang WD, Wu MW, Ou-Yang D, Zhang Q: Inflammatory myofibroblastic tumor of the head and neck. Med Oncol 2011, 28(Suppl 1):S349-S353.
• [22]Shen WQ, Cheng KJ, Bao YY, Zhou SH, Yao HT: Expression of Glut-1, HIF-1α, PI3K and p-Akt in a case of ceruminous adenoma. Head Neck Oncol 2012, 4:18. BioMed Central Full Text
• [23]Fang J, Bao YY, Zhou SH, Luo XM, Yao HT, He JF, Wang QY: Recurrent prognostic factors and expression of GLUT-1, PI3K and p-Akt in adenoid cystic carcinomas of the head and neck: clinicopathological features and biomarkers of adenoid cystic carcinoma. OncolLett 2012, 4:1234-1240.
• [24]Gort EH, Groot AJ, Derks Van De Ven TL, Van Der Groep P, Ver Laan I, Van Laar T, Van Diest PJ, van der Wall E, Shvarts A: Hypoxia-inducible factor-1a expression requires PI 3-kinase activity and correlates with Akt1 phosphorylation in invasive breast carcinomas. Oncogene 2006, 25:6123-6127.
• [25]Semenza GL: Regulation of cancer cell metabolism by hypoxia-inducible factor 1. Semin Cancer Biol 2009, 19:12-16.