Top

Published in:

01-09-2016 | Original Paper

Increased expressions of claudin 4 and 7 in atypical adenomatous hyperplasia and adenocarcinoma of the lung

Authors: Gen Yamada, Masaki Murata, Akira Takasawa, Masanori Nojima, Yuki Mori, Norimasa Sawada, Hiroki Takahashi

Published in: Medical Molecular Morphology | Issue 3/2016

Abstract

Abnormal expression of claudin (Cldn), the main constituent of tight junctions, may play a crucial role in carcinogenesis. To elucidate these abnormalities of tight junctions in lung adenocarcinoma during carcinogenesis, we examined immunohistochemical expressions of Cldn4 and Cldn7 in human lung resection materials. Lung resection specimens from 86 patients were studied, including 16 atypical adenomatous hyperplasia (AAH), 19 adenocarcinoma in situ (AIS), 32 invasive adenocarcinoma (ADC), 5 AIS with AAH, 2 ADC with AAH, 10 ADC with AIS, and 2 ADC with AIS and AAH. The immunohistochemical staining (IHC) score was defined for both the extent and intensity of staining. IHC score for Cldn4 in AIS and ADC was significantly higher than that in alveolar epithelium (AE) and AAH (p < 0.001 for both). In addition, the AAH score was significantly higher than that in AE (p < 0.001). The Cldn7 score in ADC was significantly increased compared with AE and AAH (p < 0.001 for both). These results suggested that increase of Cldn4-expression may be involved in early molecular events during carcinogenesis of adenocarcinoma, whereas increase of Cldn7-expression may be associated with tumor invasion or progression.

Available only for authorised users

Nakahara R, Yokose K, Nagai K, Nishiwaki Y, Ochiai A (2001) Atypical adenomatous hyperplasia of the lung: a clinicopathological study of 118 cases including cases with multiple atypical adenomatous hyperplasia. Thorax 56:302–305CrossRefPubMedPubMedCentral

Suzuki K, Takahashi K, Yoshida J et al (1998) Synchronous double primary lung carcinomas associated with multiple atypical adenomatous hyperplasia. Lung Cancer 19:131–139CrossRefPubMed

Kitamura H, Kameda Y, Ito T, Hayashi H (1999) Atypical adenomatous hyperplasia of the lung. Implications for the pathogenesis of peripheral lung adenocarcinoma. Am J Clin Pathol 111:610–622CrossRefPubMed

Niho S, Yokose T, Suzuki K, Kodama T, Nishiwaki Y, Mukai K (1999) Monoclonality of atypical adenomatous hyperplasia of the lung. Am J Pathol 154:249–254CrossRefPubMedPubMedCentral

Mori M, Rao SK, Proper HH, Cagle PT, Fraire AE (2001) Atypical adenomatous hyperplasia of the lung: a probable forerunner in the development of adenocarcinoma of the lung. Mod Pathol 14:72–84CrossRefPubMed

Kim HK, Jablons DM, Kim IJ (2013) Multistep progression from atypical adenomatous hyperplasia to lung adenocarcinoma: clinic-pathologic, epigenetic and genetic aspects. J Surgery 1:10

Travis WD, Brambilla E, Noguchi M et al (2011) International association for the study of lung cancer/American Thoracic Society/European Respiratory Society International multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6:244–285CrossRefPubMedPubMedCentral

Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG (2015) WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th edn. Eds. International Agency for Research on Cancer, Lyon

Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) Claudin-1and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550CrossRefPubMedPubMedCentral

10.

Sawada N (2013) Tight junction-related human diseases. Pathol Int 63:1–12CrossRefPubMed

11.

Singh AB, Sharma A, Dhawan P (2010) Claudin family of proteins and cancer: an overview. J Oncol 2010:541957CrossRefPubMedPubMedCentral

12.

Soini Y (2011) Claudins in lung diseases. Respir Res 12:70CrossRefPubMedPubMedCentral

13.

Kitamura H, Kameda Y, Ito T, Hayashi H, Nakamura N, Nakatani Y, Inayama Y, Kanisawa M (1997) Cytodifferenctiation of atypical adenomatous hyperplasia and bronchioloalveolar lung carcinoma: immunohistochemical and ultrastructural studies. Virchow Arch 431:415–424CrossRef

14.

Mori M, Kaji M, Tezuka F, Takahashi T (1998) Comparative ultrastructural study of atypical adenomatous hyperplasia and adenocarcinoma of the human lung. Ultrastruct Pathol 22:459–466CrossRefPubMed

15.

Chuman Y, Bergman A, Ueno T, Saito S, Sakaguchi K, Alaiya AA, Franzén B, Bergman T, Arnott D, Auer G, Appella E, Jörnvall H, Linder S (1999) Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas. FEBS Lett 462:129–134CrossRefPubMed

16.

Ueno T, Linder S, Elmberger G (2003) Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. British J Cancer 88:1229–1233CrossRef

17.

Leers MP, Theunissen PH, Koudstaal J, Schutte B, Ramaekers FC (1997) Trivariate flow cytometric analysis of paraffin-embedded lung cancer specimens: application of cytokeratin subtype specific antibodies to distinguish between differentiation pathways. Cytometry 27:179–188CrossRefPubMed

18.

Xu XY, Yang GY, Yang JH, Li J (2014) Analysis of clinical characteristics and differential diagnosis of the lung biopsy specimens in 99 adenocarcinoma cases and 111 squamous cell carcinoma cases: utility of an immunohistochemical panel containing CK5/6, CK34βE12, p63, CK7 and TTF-1. Pathol Res Pract 210:680–685CrossRefPubMed

19.

Kitamura H, Kameda Y, Nakamura N et al (1995) Proliferative potential and p53 overexpression in precursor and early stage lesions of bronchioloalveolar lung carcinoma. Am J Pathol 146:876–887PubMedPubMedCentral

20.

Yoo SB, Chung JH, Lee HJ, Lee CT, Jheon S, Sung SW (2010) Epidermal growth factor receptor mutation and p53 overexpression during the multistage progression of small adenocarcinoma of the lung. J Thorac Oncol 5:964–969CrossRefPubMed

21.

Moldvay J, Jackel M, Paska C, Soltesz I, Schaff Z, Kiss A (2007) Distinct claudin expression profile in histologic subtypes of lung cancer. Lung Cancer 57:159–167CrossRefPubMed

22.

Lin X, Shang X, Manorek G, Howell SB (2013) Regulation of the Epithelial-Mesenchymal Transition by Claudin-3 and Claudin-4. PLoS One 8:e67496CrossRefPubMedPubMedCentral

23.

Lahn M, Su C, Li S, Chedid M, Hanna KR, Graff JR, Sandusky GE, Ma D, Niyikiza C, Sundell KL, John WJ, Giordano TJ, Beer DG, Paterson BM, Su EW, Bumol TF (2004) Expression levels of protein kinase C-alpha in non-small-cell lung cancer. Clin Lung Cancer 6:184–189CrossRefPubMed

24.

Kyuno D, Kojima T, Ito T, Yamaguchi H, Tsujiwaki M, Takasawa A, Murata M, Tanaka S, Hirata K, Sawada N (2011) Protein kinase Cα inhibitor enhances the sensitivity of human pancreatic cancer HPAC cells to Clostridium perfringens enterotoxin via claudin-4. Cell Tissue Res 346:369–381CrossRefPubMed

25.

Lu Z, Kim do H, Fan J, Lu Q, Verbanac K, Ding L, Renegar R, Chen YH (2015) A non-tight junction function of claudin-7-Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment. Mol Cancer 14:120CrossRefPubMedPubMedCentral

26.

Nichos LS, Ashfaq R, Iacobuzio-Donahue CA (2004) Claudin 4 protein expression in primary and metastatic pancreatic cancer. Am J Clin Pathol 121:226–230CrossRef

27.

Soini Y, Takasawa A, Eskelinen M, Juvonen P, Kärjä V, Hasegawa T, Murata M, Tanaka S, Kojima T, Sawada N (2012) Expression of claudins 7 and 18 in pancreatic ductal adenocarcinoma: association with features of differentiation. J Clin Pathol 65:431–436CrossRefPubMed

28.

Ogawa M, Kojima T, Someya M, Nomura K, Takasawa A, Murata M, Tanaka S, Saito T, Sawada N (2012) Epidermal growth factor modulates claudins and tight junctional functions in ovarian cancer cell lines. Histochem Cell Biol 138:323–338CrossRefPubMed

29.

Someya M, Kojima T, Ogawa M, Ninomiya T, Nomura K, Takasawa A, Murata M, Tanaka S, Saito T, Sawada N (2013) Regulation of tight junctions by sex hormones in normal human endometrial epithelial cells and uterus cancer cell line Sawano. Cell Tissue Res 354:481–494CrossRefPubMed

30.

Keira Y, Takasawa A, Murata M, Nojima M, Takasawa K, Ogino J, Higashiura Y, Sasaki A, Kimura Y, Mizuguchi T, Tanaka S, Hirata K, Sawada N, Hasegawa T (2015) An immunohistochemical marker panel including claudin-18, maspin, and p53 improves diagnostic accuracy of bile duct neoplasms in surgical and presurgical biopsy specimens. Virchows Arch 466:265–277CrossRefPubMed

31.

Lappi-Blanco E, Lehtonen ST, Sormunen R, Merikallio HM, Soini Y, Kaarteenaho RL (2013) Divergence of tight and adherens junction factors in alveolar epithelium in pulmonary fibrosis. Hum Pathol 44:895–907CrossRefPubMed

32.

Tsujiwaki M, Murata M, Takasawa A, Hiratsuka Y, Fukuda R, Sugimoto K, Ono Y, Nojima M, Tanaka S, Hirata K, Kojima T, Sawada N (2015) Aberrant expression of claudin-4 and -7 in hepatocytes in the cirrhotic human liver. Med Mol Morphol 48:33–43CrossRefPubMed

33.

Maeda T, Murata M, Chiba H, Takasawa A, Tanaka S, Kojima T, Masumori N, Tsukamoto T, Sawada N (2012) Claudin-4-targeted therapy using Clostridium perfringens enterotoxin for prostate cancer. Prostate 72:351–360CrossRefPubMed

Title: Increased expressions of claudin 4 and 7 in atypical adenomatous hyperplasia and adenocarcinoma of the lung
Authors: Gen Yamada
Masaki Murata
Akira Takasawa
Masanori Nojima
Yuki Mori
Norimasa Sawada
Hiroki Takahashi
Publication date: 01-09-2016
Publisher: Springer Japan
Published in: Medical Molecular Morphology / Issue 3/2016
Print ISSN: 1860-1480
Electronic ISSN: 1860-1499
DOI: https://doi.org/10.1007/s00795-016-0135-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Increased expressions of claudin 4 and 7 in atypical adenomatous hyperplasia and adenocarcinoma of the lung

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2016

E-cadherin-negative acinar cell carcinoma of the pancreas: report of a case showing a solid pseudopapillary growth pattern

Inducible lymphoid clusters, iSALTs, in contact dermatitis: a new concept of acquired cutaneous immune responses

Cystic apocrine ductal carcinoma in situ with increased EGFR expression, trisomy 7, and associated focal invasion

Rapid specimen preparation to improve the throughput of electron microscopic volume imaging for three-dimensional analyses of subcellular ultrastructures with serial block-face scanning electron microscopy

Chondroitin sulfate prevents peritoneal fibrosis in mice by suppressing NF-κB activation

Erratum to: Invasive urothelial carcinoma with chordoid features may be an ominous sign predicting sarcomatoid change: a case report of a bladder carcinoma