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01-12-2013 | Original Article

Clathrin heavy chain is a useful immunohistochemical marker for esophageal squamous intraepithelial neoplasia

Authors: Kazuya Tokita, Masanori Seimiya, Kazuyuki Matsushita, Takeshi Tomonaga, Kiyotaka Onodera, Syoji Ohki, Tohru Tanizawa, Masaya Uesato, Hideaki Shimada, Hisahiro Matsubara, Yukio Nakatani, Fumio Nomura

Published in: Esophagus | Issue 4/2013

Abstract

Background

Recent advances in the endoscopic diagnosis and treatment of esophageal cancer have facilitated the detection and treatment of minute tumors, necessitating the accurate histopathological diagnosis of early esophageal cancer or precancerous lesions. This study evaluated the usefulness of immunohistochemical analysis (IHC) of clathrin heavy chain (CHC) as a marker for early esophageal cancer.

Methods

The immunoreactivity of CHC was analyzed in 409 esophageal specimens using a tissue array. Immunoreactivities of CHC, p53, and Ki67 were then compared in 44 endoscopically resected specimens.

Results

CHC expression was significantly stronger in the cytoplasm of esophageal squamous cell carcinomas compared with non-tumor specimens in the tissue array. CHC expression in endoscopic specimens was significantly stronger in the cytoplasm of high-grade intraepithelial neoplasias and superficial carcinomas than in benign squamous epithelium and low-grade intraepithelial neoplasias. The sensitivity and specificity of CHC for the diagnosis of esophageal lesions were 75 and 96 %, respectively. These accuracies were comparable with those of p53 (43 and 98 %) and Ki67 (68 and 100 %). In addition, the sensitivity was increased by using a combination of markers as follows: 80 %, CHC + p53; 78 %, CHC + Ki67; 90 %, CHC + p53 + Ki67.

Conclusions

CHC detected by IHC may be a useful marker for the pathological diagnosis of esophageal squamous intraepithelial neoplasia.

Lerut T, Coosemans W, De Leyn P, Van Raemdonck D, Deneffe G, Decker G. Treatment of esophageal carcinoma. Chest. 1999;116:463S–5S.PubMedCrossRef

Mroczko B, Kozlowski M, Groblewska M, Lukaszewicz M, Niklinski J, Jelski W, Laudanski J, Chyczewski L, Szmitkowski M. The diagnostic value of the measurement of matrix metalloproteinase 9 (MMP-9), squamous cell cancer antigen (SCC) and carcinoembryonic antigen (CEA) in the sera of esophageal cancer patients. Clin Chim Acta. 2008;389:61–6.PubMedCrossRef

Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Gunji Y, Kobayashi S, Hayashi H, Ochiai T. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133:486–94.PubMedCrossRef

Shimada H, Takeda A, Arima M, Okazumi S, Matsubara H, Nabeya Y, Funami Y, Hayashi H, Gunji Y, Suzuki T, Kobayashi S, Ochiai T. Serum p53 antibody is a useful tumor marker in superficial esophageal squamous cell carcinoma. Cancer. 2000;89:1677–83.PubMedCrossRef

Shimada H, Yajima S, Oshima Y, Hiwasa T, Tagawa M, Matsushita K, Nomura F. Impact of serum biomarkers on esophageal squamous cell carcinoma. Esophagus, Inpress.

Mori M, Adachi Y, Matsushima T, Matsuda H, Kuwano H, Sugimachi K. Lugol staining pattern and histology of esophageal lesions. Am J Gastroenterol. 1993;88:701–5.PubMed

Seimiya M, Tomonaga T, Matsushita K, Sunaga M, Oh-Ishi M, Kodera Y, Maeda T, Takano S, Togawa A, Yoshitomi H, Otsuka M, Yamamoto M, Nakano M, Miyazaki M, Nomura F. Identification of novel immunohistochemical tumor markers for primary hepatocellular carcinoma; clathrin heavy chain and form imino transferase cyclo deaminase. Hepatology. 2008;48:519–30.PubMedCrossRef

Kirchhausen T. Clathrin. Annu Rev Biochem. 2000;69:699–727.PubMedCrossRef

Royle SJ, Lagnado L. Trimerisation is important for the function of clathrin at the mitotic spindle. J Cell Sci. 2006;119:4071–8.PubMedCrossRef

10.

Ohata H, Ota N, Shirouzu M, Yokoyama S, Yokota J, Taya Y, Enari M. Identification of a function-specific mutation of clathrin heavy chain (CHC) required for p53 transactivation. J Mol Biol. 2009;394:460–71.PubMedCrossRef

11.

Squamous cell carcinoma of the oesophagus. World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of the Digestive System; 2000 pp. 11–19.

12.

Dawsey SM, Lewin KJ, Wang GQ, Liu FS, Nieberg RK, Yu Y, Li JY, Blot WJ, Li B, Taylor PR. Squamous esophageal histology and subsequent risk of squamous cell carcinoma of the esophagus. A prospective follow-up study from Linxian, China. Cancer. 1994;74:1686–92.PubMedCrossRef

13.

Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Flejou JF, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner F, Price AB, Rubio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000;47:251–5.PubMedCrossRef

14.

Dixon MF. Gastrointestinal epithelial neoplasia: Vienna revisited. Gut. 2002;51:130–1.PubMedCrossRef

15.

Wang GQ, Abnet CC, Shen Q, Lewin KJ, Sun XD, Roth MJ, Qiao YL, Mark SD, Dong ZW, Taylor PR, Dawsey SM. Histological precursors of oesophageal squamous cell carcinoma: results from a 13 year prospective follow up study in a high risk population. Gut. 2005;54:187–92.PubMedCrossRef

16.

Shimizu M, Nagata K, Yamaguchi H, Kita H. Squamous intraepithelial neoplasia of the esophagus: past, present, and future. J Gastroenterol. 2009;44:103–12.PubMedCrossRef

17.

Xu M, Jin YL, Fu J, Huang H, Chen SZ, Qu P, Tian HM, Liu ZY, Zhang W. The abnormal expression of retinoic acid receptor-beta, p 53 and Ki67 protein in normal, premalignant and malignant esophageal tissues. World J Gastroenterol. 2002;8:200–2.PubMed

18.

Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, Levine AJ. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988;8:531–9.PubMed

19.

Bennett WP, Hollstein MC, Metcalf RA, Welsh JA, He A, Zhu SM, Kusters I, Resau JH, Trump BF, Lane DP, et al. p53 mutation and protein accumulation during multistage human esophageal carcinogenesis. Cancer Res. 1992;52:6092–7.PubMed

20.

Gao H, Wang LD, Zhou Q, Hong JY, Huang TY, Yang CS. p53 tumor suppressor gene mutation in early esophageal precancerous lesions and carcinoma among high-risk populations in Henan. China. Cancer Res. 1994;54:4342–6.

21.

Kobayashi M, Kawachi H, Takizawa T, Uchida K, Sekine M, Kumagai J, Momma K, Nemoto T, Akashi T, Funata N, Eishi Y, Koike M. p53 Mutation analysis of low-grade dysplasia and high-grade dysplasia/carcinoma in situ of the esophagus using laser capture microdissection. Oncology. 2006;71:237–45.PubMedCrossRef

22.

Gerdes J. Ki-67 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies. Semin Cancer Biol. 1990;1:199–206.PubMed

23.

Wang WC, Wu TT, Chandan VS, Lohse CM, Zhang L. Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia. Hum Pathol. 2011;42:1430–7.PubMedCrossRef

Title: Clathrin heavy chain is a useful immunohistochemical marker for esophageal squamous intraepithelial neoplasia
Authors: Kazuya Tokita
Masanori Seimiya
Kazuyuki Matsushita
Takeshi Tomonaga
Kiyotaka Onodera
Syoji Ohki
Tohru Tanizawa
Masaya Uesato
Hideaki Shimada
Hisahiro Matsubara
Yukio Nakatani
Fumio Nomura
Publication date: 01-12-2013
Publisher: Springer Japan
Published in: Esophagus / Issue 4/2013
Print ISSN: 1612-9059
Electronic ISSN: 1612-9067
DOI: https://doi.org/10.1007/s10388-013-0381-9

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Abstract

Background

Methods

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Conclusions

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