Adrenal cortical neoplasms: a study of clinicopathological features related to epidermal growth factor receptor gene status

Diagnostic Pathology

Zhiyong Liang¹  Shafei Wu¹  Xuan Zeng¹  Jian Sun¹  Jie Gao¹  Cuiping Wang¹  Jing Zhang¹ 

[1] Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuai Fu Yuan Hu Tong, Beijing 100730, People’s Republic of China

关键词: Mutation;    Fluorescence in situ hybridization;    Epidermal growth factor receptor;    Adrenal cortical neoplasm;   

Others  :  1228637
DOI  :  10.1186/1746-1596-9-19

 received in 2013-07-19, accepted in 2013-12-18,  发布年份 2014

【 摘 要 】

Background

Adrenocortical carcinoma (ACC) is a rare but highly malignant neoplasm with limited treatment options.

Methods

In this study, the clinicopathological features of 22 ACCs and 22 adrenocortical adenomas (ACA) were analyzed, and the EGFR protein expression, EGFR gene mutation status and EGFR gene copy number alteration of all tumors were examined using immunohistochemistry, fluorescence in situ hybridization (FISH), and the Scorpion Amplification Refractory Mutation System (ARMS), respectively.

Results

EGFR protein expression was detected in 63.6% of the ACC samples, and EGFR FISH was positive in 50% of the ACC samples (all were high polysomy on chromosome 7). In contrast, 27.3% of the ACA samples demonstrated EGFR expression, and none of the ACA samples tested positive by FISH. There were significant differences between the ACC and ACA in terms of protein expression (P = 0.035) and gene copy number alterations (P < 0.001).

Conclusions

EGFR protein expression and high polysomy on chromosome 7 are frequent abnormalities in ACC than in ACA.

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/2068470757103500 webcite.

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Allolio B, Fassnacht M: Clinical review: adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 2006, 91:2027-2037.
• [2]Kuruba R, Gallagher SF: Current management of adrenal tumors. Curr Opin Oncol 2008, 20:34-46.
• [3]Weiss LM, Medeiros LJ, Vickery AL Jr: Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989, 13:202-206.
• [4]Sasano H, Suzuki T, Moriya T: Recent advances in histopathology and immunohistochemistry of adrenocortical carcinoma. Endocr Pathol 2006, 17:345-354.
• [5]Volante M, Buttigliero C, Greco E, Berruti A, Papotti M: Pathological and molecular features of adrenocortical carcinoma: an update. J Clin Pathol 2008, 61:787-793.
• [6]Libe R, Fratticci A, Bertherat J: Adrenocortical cancer: pathophysiology and clinical management. Endocr Relat Cancer 2007, 14:13-28.
• [7]Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS: Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006, 366:2-16.
• [8]Sibilia M, Kroismayr R, Lichtenberger BM, Natarajan A, Hecking M, Holcmann M: The epidermal growth factor receptor: from development to tumorigenesis. Differentiation 2007, 75:770-787.
• [9]Sharma SV, Bell DW, Settleman J, Haber DA: Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007, 7:169-181.
• [10]Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan- refractory metastatic colorectal cancer. N Engl J Med 2004, 351:337-345.
• [11]Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L: National Cancer Institute of Canada Clinical Trials Group:Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005, 353:123-132.
• [12]Sasano H, Suzuki T, Shizawa S, Kato K, Nagura H: Transforming growth factor alpha, epidermal growth factor, and epidermal growth factor receptor expression in normal and diseased human adrenal cortex by immunohistochemistry and in situ hybridization. Mod Pathol 1994, 7:741-774.
• [13]Kamio T, Shigematsu K, Sou H, Kawai K, Tsuchiyama H: Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma. Hum Pathol 1990, 21:277-282.
• [14]Nakamura M, Miki Y, Akahira J, Morimoto R, Satoh F, Ishidoya S, Arai Y, Suzuki T, Hayashi Y, Sasano H: An analysis of potential surrogate markers of target-specific therapy in archival materials of adrenocortical carcinoma. Endocr Pathol 2009, 20:17-23.
• [15]Adam P, Hahner S, Hartmann M, Heinrich B, Quinkler M, Willenberg HS, Saeger W, Sbiera S, Schmull S, Voelker HU, Ströbel P, Allolio B, Fassnacht M: Epidermal growth factor receptor in adrenocortical tumors: analysis of gene sequence, protein expression and correlation with clinical outcome. Mod Pathol 2010, 23:1596-1604.
• [16]Kotoula V, Sozopoulos E, Litsiou H, Fanourakis G, Koletsa T, Voutsinas G, Tseleni-Balafouta S, Mitsiades CS, Wellmann A, Mitsiades N: Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas. Endocr Relat Cancer 2009, 16:565-572.
• [17]Zhang J, Sun J, Liang Z, Gao J, Zeng X, Liu T: Myxoid Adrenocortical Neoplasms A Study of the Clinicopathologic Features and EGFR Gene Status of Ten Chinese Cases. Am J Clin Pathol 2011, 136:783-792.
• [18]Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C, Kalsheker N, Smith JC, Markham AF: Analysis of any point mutation in DNA: The amplification refractory mutation system (ARMS). Nucleic Acids Res 1989, 17:2503-2516.
• [19]Thelwell N, Millington S, Solinas A, Booth J, Brown T: Mode of action and application of scorpion primers to mutation detection. Nucleic Acids Res 2000, 28:3752-3761.
• [20]Whitcombe D, Theaker J, Guy SP, Brown T, Little S: Detection of PCR products using self-probing amplicons and fluorescence. Nat Biotechnol 1999, 17:804-807.
• [21]Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, Haney J, Witta S, Danenberg K, Domenichini I, Ludovini V, Magrini E, Gregorc V, Doglioni C, Sidoni A, Tonato M, Franklin WA, Crino L, Bunn PA Jr, Varella-Garcia M: Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 2005, 97:643-655.
• [22]Thatcher N: The place of targeted therapy in the patient management of non-small cell lung cancer. Lung Cancer 2007, 57(Suppl 2):S18-S23.
• [23]Loprevite M, Tiseo M, Chiaramondia M, Capelletti M, Bozzetti C, Bortesi B, Naldi N, Nizzoli R, Dadati P, Kunkl A, Zennaro D, Lagrasta C, Campanini N, Spiritelli E, Camisa R, Grossi F, Rindi G, Franciosi V, Ardizzoni A: Buccal mucosa cells as in vivo model to evaluate gefitinib activity in patients with advanced non small cell lung cancer. Clin Cancer Res 2007, 13:6518-6526.