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Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas.
Oncol Rep 2003 Jan-Feb; 10(1):21-5OR

Abstract

Intraductal papillary-mucinous tumors (IPMTs) of the pancreas are characterized by dilated pancreatic ducts and ductules that are lined by tall columnar mucin-producing neoplastic epithelial cells. IPMTs have been suggested to be distinct neoplasms with a less aggressive phenotype than that of conventional ductal adenocarcinomas of the pancreas. Molecular mechanisms underlying tumorigenesis of IPMTs are beginning to be characterized. Allelic losses have frequently been detected at 9p, 17p, and 18q, suggesting that inactivation of tumor suppressor genes at these loci play a role in tumorigenesis of IPMTs. Using immunohistochemistry, we analyzed 38 IPMTs, including 9 hyperplasia, 16 adenoma, and 13 carcinoma tissues, for expression of p53, Ki-67, p16, and SMAD4. Nuclear p53 expression was observed in 5 (38%) of 13 carcinoma tissues but not in hyperplasia or adenoma tissues. Partial loss of p16 expression was observed in 9 (56%) and 12 (92%) of the 16 adenoma and 13 carcinoma tissues, respectively. Partial loss of p16 expression was observed even in adenomas with mild atypia. Partial loss of SMAD4 expression was observed in 6 (38%) and 12 (92%) of the 16 adenoma and 13 carcinoma tissues, respectively. The SMAD4 negative index was significantly higher in invasive carcinomas than in non-invasive carcinomas. Our results suggest that loss of p16 is an early event and p53 alteration is a late event during the progression of IPMTs. SMAD4 inactivation appears to be an early event but also involved in invasive tumor growth. Our results suggest that these alterations accumulate during the progression of IPMTs, reflecting results of analysis of allelic losses that showed a stepwise accumulation of genetic changes during progression.

Authors+Show Affiliations

First Department of Internal Medicine, Sapporo Medical University, Chuo-ku, Japan. ssasaki@sapmed.ac.jp

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12469138

Citation

Sasaki, Shigeru, et al. "Differential Roles of Alterations of P53, P16, and SMAD4 Expression in the Progression of Intraductal Papillary-mucinous Tumors of the Pancreas." Oncology Reports, vol. 10, no. 1, 2003, pp. 21-5.
Sasaki S, Yamamoto H, Kaneto H, et al. Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas. Oncol Rep. 2003;10(1):21-5.
Sasaki, S., Yamamoto, H., Kaneto, H., Ozeki, I., Adachi, Y., Takagi, H., ... Imai, K. (2003). Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas. Oncology Reports, 10(1), pp. 21-5.
Sasaki S, et al. Differential Roles of Alterations of P53, P16, and SMAD4 Expression in the Progression of Intraductal Papillary-mucinous Tumors of the Pancreas. Oncol Rep. 2003;10(1):21-5. PubMed PMID: 12469138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas. AU - Sasaki,Shigeru, AU - Yamamoto,Hiroyuki, AU - Kaneto,Hiroyuki, AU - Ozeki,Itaru, AU - Adachi,Yasuyo, AU - Takagi,Hideyasu, AU - Matsumoto,Takeshi, AU - Itoh,Hideto, AU - Nagakawa,Tatsuya, AU - Miyakawa,Hiroyuki, AU - Muraoka,Shunji, AU - Fujinaga,Akira, AU - Suga,Toshihiro, AU - Satoh,Masaaki, AU - Itoh,Fumio, AU - Endo,Takao, AU - Imai,Kohzoh, PY - 2002/12/7/pubmed PY - 2003/6/7/medline PY - 2002/12/7/entrez SP - 21 EP - 5 JF - Oncology reports JO - Oncol. Rep. VL - 10 IS - 1 N2 - Intraductal papillary-mucinous tumors (IPMTs) of the pancreas are characterized by dilated pancreatic ducts and ductules that are lined by tall columnar mucin-producing neoplastic epithelial cells. IPMTs have been suggested to be distinct neoplasms with a less aggressive phenotype than that of conventional ductal adenocarcinomas of the pancreas. Molecular mechanisms underlying tumorigenesis of IPMTs are beginning to be characterized. Allelic losses have frequently been detected at 9p, 17p, and 18q, suggesting that inactivation of tumor suppressor genes at these loci play a role in tumorigenesis of IPMTs. Using immunohistochemistry, we analyzed 38 IPMTs, including 9 hyperplasia, 16 adenoma, and 13 carcinoma tissues, for expression of p53, Ki-67, p16, and SMAD4. Nuclear p53 expression was observed in 5 (38%) of 13 carcinoma tissues but not in hyperplasia or adenoma tissues. Partial loss of p16 expression was observed in 9 (56%) and 12 (92%) of the 16 adenoma and 13 carcinoma tissues, respectively. Partial loss of p16 expression was observed even in adenomas with mild atypia. Partial loss of SMAD4 expression was observed in 6 (38%) and 12 (92%) of the 16 adenoma and 13 carcinoma tissues, respectively. The SMAD4 negative index was significantly higher in invasive carcinomas than in non-invasive carcinomas. Our results suggest that loss of p16 is an early event and p53 alteration is a late event during the progression of IPMTs. SMAD4 inactivation appears to be an early event but also involved in invasive tumor growth. Our results suggest that these alterations accumulate during the progression of IPMTs, reflecting results of analysis of allelic losses that showed a stepwise accumulation of genetic changes during progression. SN - 1021-335X UR - https://www.unboundmedicine.com/medline/citation/12469138/Differential_roles_of_alterations_of_p53_p16_and_SMAD4_expression_in_the_progression_of_intraductal_papillary_mucinous_tumors_of_the_pancreas_ L2 - http://www.spandidos-publications.com/or/10/1/21 DB - PRIME DP - Unbound Medicine ER -