Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases.
The aim of the study was to investigate the correlation between claudin (CLDN) protein expression and clinicopathological parameters as well as survival in histological subtypes of non-small cell lung cancer. Archived surgical resection specimens of 137 pathologic stage I primary bronchial cancers including 49 adenocarcinomas of non-lepidic variants (ADC), 46 adenocarcinomas of lepidic variants (L-ADC), and 42 squamous cell carcinomas (SCC) were examined. Immunohistochemistry (IHC) using antibodies against CLDN1,-2,-3,-4,-7 proteins as well as semiquantitative estimation (IHC scores 0-5) were performed. Claudin IHC scores of L-ADC differed significantly from ADC (CLDN1: p = 0.009, CLDN2: p = 0.005, CLDN3: p = 0.004, CLDN4: p = 0.001, CLDN7: p < 0.001, respectively) and SCC (CLDN1: p < 0.001, CLDN3: p < 0.001, CLDN7: p < 0.001, respectively). Highly significant CLDN3-CLDN4 parallel expression could be demonstrated in ADC and L-ADC (p < 0.001 in both), which was not observed in SCC (p = 0.131). ADC and SCC showed no correlation with smoking, whereas in case of L-ADC heavier smoking correlated with higher CLDN3 expression (p = 0.020). Regarding claudin expression and survival, in SCC significant correlation could be demonstrated between CLDN1 IHC positivity and better survival (p = 0.038). In NSCLC as a whole, high CLDN2 expression proved to be a better prognostic factor when compared with cases where CLDN2 IHC score was 0-1 vs. 2-5 (p = 0.009), however, when analyzed separately, none of the histological subgroups showed correlation between CLDN2 expression and overall survival. The claudin expression pattern was significantly different not only between the SCC-ADC and SCC-L-ADC but also between the L-ADC and ADC histological subgroups, which strongly underlines that L-ADC represents a distinct entity within the ADC group. CLDN1 overexpression is a good prognostic factor in NSCLC, but only in the SCC subgroup.
National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, H-1122, Hungary. drmoldvay@hotmail.com.|Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Ráth György u. 7-9, Budapest, H-1122, Hungary. drmoldvay@hotmail.com.
Judit
J
Moldvay
Department of Pulmonology, Semmelweis University, Diósárok u. 1/c, Budapest, H-1125, Hungary.
Katalin
K
Fábián
Department of Pathology, Military Hospital, Róbert Károly krt. 44, Budapest, H-1134, Hungary.
Márta
M
Jäckel
Centre for Cancer Research and Cell Biology, Queen's University, 97 Lisburn Road, Belfast, BT9 7AE, Ireland.
Zsuzsanna
Z
Németh
National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, H-1122, Hungary.
Krisztina
K
Bogos
Department of Surgery, University of Szeged, Szőkefalvi-Nagy u. 6, Szeged, H-6720, Hungary.
József
J
Furák
Department of Pathology, University of Szeged, Állomás u. 2, Szeged, 6720, Hungary.
László
L
Tiszlavicz
Department of Pathology, National Institute of Oncology, Ráth György u. 7-9, Budapest, H-1122, Hungary.
János
J
Fillinger
National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, H-1122, Hungary.|Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Ráth György u. 7-9, Budapest, H-1122, Hungary.|Division of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Spitalgasse 23,, 1090, Vienna, Austria.
Balázs
B
Döme
2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, H-1091, Hungary.
Zsuzsa
Z
Schaff
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D062445:Claudin-1 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
C568108:CLDN1 protein, human; D062445:Claudin-1
Claudin; Immunohistochemistry; Lung cancer; Survival
Hum Pathol. 2010 Jul;41(7):944-50
20334898
Oncogene. 2003 Apr 3;22(13):2021-33
12673207
Am J Respir Crit Care Med. 2009 Jan 15;179(2):123-33
18787218
Lung Cancer. 2007 Aug;57(2):159-67
17418912
BJU Int. 2010 Mar;105(5):716-22
19818082
J Thorac Oncol. 2013 Jan;8(1):52-61
23242438
J Cardiothorac Surg. 2013 Apr 16;8:95
23591077
Mod Pathol. 2005 Apr;18(4):511-8
15475928
BMC Cancer. 2013 Dec 10;13:586
24321518
J Clin Oncol. 2013 Mar 10;31(8):992-1001
23401443
Eur J Cancer. 2011 Mar;47(4):620-30
21106366
Clin Cancer Res. 2008 Nov 1;14(21):7035-42
18981000
Appl Immunohistochem Mol Morphol. 2014;22(2):125-31
23702644
Oral Oncol. 2013 Oct;49(10 ):998-1005
23953778
Med Electron Microsc. 2003 Sep;36(3):147-56
14505058
Chin Med J (Engl). 2013;126(19):3668-74
24112161
J Surg Res. 2011 May 15;167(2):e185-91
20462599
Eur J Cancer. 2011 Apr;47(6):918-25
21134740
Clin Exp Metastasis. 2011 Jan;28(1):55-63
20963473
J Thorac Oncol. 2011 Feb;6(2):244-85
21252716
Oncol Lett. 2010 May;1(3):501-505
22966332