title: An association between nuclear morphology and immunohistochemical expression of p53 and p16INK4A in lung cancer cells.
abstract: Nuclear atypia is one of the most important morphological features used to diagnose malignant neoplasms. The potential molecular alteration that causes nuclear atypia remains unknown. P53 and p16INK4A play crucial roles in cell cycle checkpoints and repairing DNA damage to maintain integrity of the genome. Thus, inactivation of p53 and p16INK4A has been hypothesized to alter the chromatin structure and result in nuclear atypia. This study examined 201 primary lung cancers for the immunohistochemical expression of p53 and p16INK4A, and analyzed potential associations with the essential elements of nuclear atypia, such as nuclear size, circularity of the outline, and the density and granularity of chromatin. Tumors that expressed high levels of p53 had larger nuclei with higher chromatin density and distorted nuclear outlines. Tumors that expressed low levels of p16INK4 had larger nuclei with distorted nuclear outlines. Thus, alterations in p53 and p16INK4A may be the potential cause of nuclear atypia in neoplastic cells.
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan, kojixok@med.yokohama-cu.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Okudela
mesh_terms: D002467:Cell Nucleus / Q000473:pathology*; D002843:Chromatin / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002843:Chromatin; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53
references.citation: Curr Opin Cell Biol. 2006 Jun;18(3):307-16
references.pmid: 16687245
references.citation: Cancer Lett. 2009 Aug 8;280(2):168-76
references.pmid: 19103471
references.citation: J Cell Sci. 2009 Apr 15;122(Pt 8):1071-9
references.pmid: 19339546
references.citation: Folia Histochem Cytobiol. 2006;44(3):143-54
references.pmid: 16977793
references.citation: Oncogene. 1992 Apr;7(4):743-9
references.pmid: 1565469
references.citation: Cancer Biol Ther. 2005 Feb;4(2):134-8
references.pmid: 15725725
references.citation: Cancer Res. 1997 Feb 15;57(4):747-52
references.pmid: 9044855
references.citation: Oncol Rep. 2004 Aug;12(2):389-95
references.pmid: 15254707
references.citation: Am J Surg Pathol. 2010 Feb;34(2):243-55
references.pmid: 20061937
references.citation: Oncol Rep. 2010 Dec;24(6):1599-604
references.pmid: 21042757
references.citation: Lung Cancer. 2005 Dec;50(3):385-91
references.pmid: 16140420
references.citation: J Cell Biol. 2010 Feb 8;188(3):369-81
references.pmid: 20123995
references.citation: Curr Biol. 2010 Mar 23;20(6):R285-95
references.pmid: 20334839
references.citation: Adv Exp Med Biol. 2010;676:93-103
references.pmid: 20687471
references.citation: Nat Rev Cancer. 2004 Dec;4(12):988-93
references.pmid: 15573120
references.citation: J Genet Genomics. 2010 Mar;37(3):159-72
references.pmid: 20347825
references.citation: Annu Rev Pharmacol Toxicol. 2005;45:629-56
references.pmid: 15822191
references.citation: Nat Rev Cancer. 2010 May;10(5):342-52
references.pmid: 20414202
references.citation: Oncogene. 2010 Apr 1;29(13):1929-40
references.pmid: 20062083
references.citation: Genet Med. 2009 Oct;11(10):687-94
references.pmid: 19668082