Expression of p63 and its Isoform, deltaNp63, in Non-Small Cell Lung Carcinoma
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Background : Several studies have been conducted on the role of the p63 gene family in nonsmall cell lung carcinoma (NSCLC). Nevertheless, the role of these genes in the development and progression of NSCLC remains controversial. This study was designed to examine the expression and clinicopathologic significance of the p63 family in NSCLC. Methods : Immunohistochemical staining was performed on 92 cases of NSCLC (47 squamous cell carcinomas [SqCCs] and 45 adenocarcinomas [ACs]) using tissue microarray blocks. The results were analyzed and correlated with clinicopathologic data. Results : The expression of deltaNp63 (△Np63) was elevated in SqCC (39/47), but not in AC (2/45; p<0.01). Both p63 and Np63 had high expression in 39 SqCCs; p63 and △Np63 also had a similar geomorphologic distribution in most positive tumors. The expression of △Np63 was correlated with histologic type, gender, pT stage, p53 expression, and p63 expression. pT and pN stages were independent factors in survival (p<0.05, respectively). Conclusions : The major p63 isoform in NSCLC, △Np63, had a strong correlation with p53 and p63, and was exclusively expressed in SqCC. However, our findings suggest that △Np63 was not an independent prognostic factor for NSCLC.
Abstract
Background : Several studies have been conducted on the role of the p63 gene family in nonsmall cell lung carcinoma (NSCLC). Nevertheless, the role of these genes in the development and progression of NSCLC remains controversial. This study was designed to examine the expression and clinicopathologic significance of the p63 family in NSCLC. Methods : Immunohistochemical staining was performed on 92 cases of NSCLC (47 squamous cell carcinomas [SqCCs] and 45 adenocarcinomas [ACs]) using tissue microarray blocks. The results were analyzed and correlated with clinicopathologic data. Results : The expression of deltaNp63 (△Np63) was elevated in SqCC (39/47), but not in AC (2/45; p<0.01). Both p63 and Np63 had high expression in 39 SqCCs; p63 and △Np63 also had a similar geomorphologic distribution in most positive tumors. The expression of △Np63 was correlated with histologic type, gender, pT stage, p53 expression, and p63 expression. pT and pN stages were independent factors in survival (p<0.05, respectively). Conclusions : The major p63 isoform in NSCLC, △Np63, had a strong correlation with p53 and p63, and was exclusively expressed in SqCC. However, our findings suggest that △Np63 was not an independent prognostic factor for NSCLC.
참고문헌 (28)
- Yang A, "p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities", Mol Cell, 2, pp.305~316 (1998)
- Petitjean A, "Caron de Fromentel C. TP63 gene in stress response and carcinogenesis: a broader role than expected", Bull Cancer, 93, pp.E126~E135 (2006)
- Irwin MS, "p53 family update: p73 and p63 develop their own identities", Cell Growth Differ, 12, pp.337~349 (2001)
- Koster MI, "p63 is the molecular switch for initiation of an epithelial stratification program", Genes Dev, 18, pp.126~131 (2004)
- Byrne C, "Programming gene expression in developing epidermis", Development, 120, pp.2369~2383 (1994)
- Barbieri CE, "IGFBP-3 is a direct target of transcriptional regulation by Delta-Np63alpha in squamous epithelium", Cancer Res, 65, pp.2314~2320 (2005)
- Ghioni P, "Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains", Mol Cell Biol, 22, pp.8659~8668 (2002)
- Serber Z, "A C-terminal inhibitory domain controls the activity of p63 by an intramolecular mechanism", Mol Cell Biol, 22, pp.8601~8611 (2002)
- Patturajan M, "DeltaNp63 induces betacatenin nuclear accumulation and signaling", Cancer Cell, 1, pp.369~379 (2002)
- Koster MI, "Reactivation of developmentally expressed p63 isoforms predisposes to tumor development and progression", Cancer Res, 66, pp.3981~3986 (2006)
- Hu H, "Elevated expression of p63 protein in human esophageal squamous cell carcinomas", Int J Cancer, 102, pp.580~583 (2002)
- Nylander K, "Differential expression of p63 isoforms in normal tissues and neoplastic cells", J Pathol, 198, pp.417~427 (2002)
- Nishi H, "Mutation and transcription analyses of the p63 gene in cervical carcinoma", Int J Oncol, 15, pp.1149~1153 (1999)
- Malaguarnera R, "p53 family proteins in thyroid cancer", Endocr Relat Cancer, 14, pp.43~60 (2007)
- Massion PP, "Role of p63 amplification and overexpression in lung cancer development", Chest, 125(5), pp.102S~ (2004)
- Massion PP, "Significance of p63 amplification and overexpression in lung cancer development and prognosis", Cancer Res, 63, pp.7113~7121 (2003)
- Sobin LH, "Lung. in: TNM classification of malignant tumours", pp.99~103 (2002), Wiley-Liss
- Travis WD, "Tumours of the lung. in: World Health Organization classification of tumours. pathology and genetics of tumours of the lung, pleura, thymus and heart" (2004), IARC Press
- Marin MC, "p63 and p73: old members of a new family", Biochim Biophys Acta, 1470, pp.M93~M100 (2000)
- Melino G, "Functional regulation of p73 and p63: development and cancer", Trends Biochem Sci, 28, pp.663~670 (2003)
- Crook T, "High level expression of deltaN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)", Oncogene, 19, pp.3439~3444 (2000)
- Hibi K, "AIS is an oncogene amplified in squamous cell carcinoma", Proc Natl Acad Sci, pp.5462~5467 (2000)
- Tannapfel A, "Expression of the p53 homologues p63 and p73 in multiple simultaneous gastric cancer", J Pathol, 195, pp.163~170 (2001)
- Malaguarnera R, "The p53-homologue p63 may promote thyroid cancer progression", Endocr Relat Cancer, 12, pp.953~971 (2005)
- Mitsudomi T, "Prognostic significance of p53 alterations in patients with non-small cell lung cancer:a meta-analysis", Clin Cancer Res, 6, pp.4055~4063 (2000)
- Iwata T, "A lack of prognostic significance regarding deltaNp63 immunoreactivity in lung cancer", Lung Cancer, 50, pp.67~73 (2005)
- Narahashi T, "Cytoplasmic localization of p63 is associated with poor patient survival in lung adenocarcinoma", Histopathology, 49, pp.349~357 (2006)
- King KE, "Unique domain functions of p63 isotypes that differentially regulate distinct aspects of epidermal homeostasis", Carcinogenesis, 27, pp.53~63 (2006)
