title: Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung.
abstract: Recent molecular biological studies have identified podoplanin as a candidate cancer stem cell (CSC) marker in squamous cell carcinoma (SqCC). The purpose of this study was to examine the expression pattern of podoplanin, and the other stem cell markers CD44 and p63, and their relationship to clinico-pathological features including survival in pulmonary SqCC. We examined histologically the expression of podoplanin, CD44, and p63 in 162 consecutive SqCC by immunostaining. Podoplanin expression was observed in 107 (66%) tumors, CD44 in 145 (89.5%), and p63 in 151 (93.2%), respectively. In 95.3% of the podoplanin-positive tumors, tumor cells showing strong expression were localized in the periphery of the tumor nests. However, this peripheral localization was observed in only 55.9% of the CD44-positive and 43% of p63-positive tumors. In 88.8% of the podoplanin-positive tumors, positive cells were localized more peripherally in the tumor nests than CD44- or p63-positive cells and when CD44 and p63 expressions were compared in these podoplanin-positive tumors, p63-positive layers in the periphery of the tumor nests were broader compared to CD44-positive layers. These findings suggest tumor cells are aligned in the "hierarchical distribution pattern" according to the expression of these three markers. Patients who had podoplanin-positive tumors with the "hierarchical pattern" resulted in significantly better overall survival than those who had podoplanin-negative tumors (P = 0.043). These results suggest that podoplanin expression would reflect the most immature status in the differentiation process of SqCC, and SqCC with hierarchical expression would be a well-organized tumor group with lower biological aggressiveness based on the CSC concept.
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Shimada
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.forename: Naho
authors.initials: N
authors.lastname: Atsumi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamane
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hishida
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Nishimura
authors.forename: Junji
authors.initials: J
authors.lastname: Yoshida
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ikeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000032:analysis*; D060149:Tetraspanin 30; D000098853:Podoplanin
chemical_list: D015703:Antigens, CD; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; C497483:CD44 protein, human; C554586:CD63 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin
references.citation: Nature. 2008 Dec 4;456(7222):593-8
references.pmid: 19052619
references.citation: J Thorac Oncol. 2006 Oct;1(8):847-55
references.pmid: 17409969
references.citation: Biochem Biophys Res Commun. 2008 Aug 15;373(1):36-41
references.pmid: 18539139
references.citation: Cancer. 2006 Aug 1;107(3):563-9
references.pmid: 16804930
references.citation: J Clin Oncol. 2003 Jun 15;21(12):2237-46
references.pmid: 12748244
references.citation: Nat Rev Mol Cell Biol. 2000 Dec;1(3):199-207
references.pmid: 11252895
references.citation: Lab Invest. 2002 Sep;82(9):1255-7
references.pmid: 12218087
references.citation: Gene. 2006 Aug 15;378:52-7
references.pmid: 16766141
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3156-61
references.pmid: 11248048
references.citation: Annu Rev Cell Dev Biol. 2001;17:387-403
references.pmid: 11687494
references.citation: Hum Pathol. 2008 Jul;39(7):1096-102
references.pmid: 18495204
references.citation: Cancer Res. 2002 Apr 15;62(8):2281-6
references.pmid: 11956084
references.citation: N Engl J Med. 2005 Jul 14;353(2):123-32
references.pmid: 16014882
references.citation: Mod Pathol. 2006 May;19(5):708-16
references.pmid: 16528371
references.citation: Int J Cancer. 2005 Mar 1;113(6):899-910
references.pmid: 15515019
references.citation: Cancer Res. 2008 Sep 1;68(17):6877-83
references.pmid: 18757399
references.citation: J Cell Sci. 2006 Nov 1;119(Pt 21):4541-53
references.pmid: 17046996
references.citation: Cancer. 1997 Jul 1;80(1):34-41
references.pmid: 9210706
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8
references.pmid: 17210912
references.citation: Hum Pathol. 2002 Sep;33(9):921-6
references.pmid: 12378518
references.citation: Cell Growth Differ. 2001 Jul;12(7):337-49
references.pmid: 11457731
references.citation: J Clin Oncol. 2008 Jun 10;26(17):2883-9
references.pmid: 18539968
references.citation: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5462-7
references.pmid: 10805802
references.citation: J Pathol. 2007 Dec;213(4):384-91
references.pmid: 17935121