BACKGROUND: Appendiceal tumors are rare, and their pathogenesis is not well known. DNA damage response (DDR) is a sequence from the detection of damaged DNA to the repair, and its impairment is implicated in the progression of cancers. The aim of the current study is to explore the expression and phosphorylation of checkpoint kinase 2 (Chk2) and TP53, which are key molecules in DDR, and their clinicopathological correlation in the appendiceal tumors. METHODS: Chk2, phosphorylated Chk2 (pChk2), and TP53 were immunostained in 4 cases of adenoma (AD), 5 non-mucinous adenocarcinomas (AC), 29 low-grade appendiceal mucinous neoplasms (LAMN), and 7 mucinous adenocarcinomas (MAC). Ki-67 labeling index was also evaluated by immunostaining. RESULTS: Chk2 was highly expressed in the nuclei of all the appendiceal tumors. While pChk2 was high in AD, LAMN, and MAC, it was reduced in AC. Nuclear positive reaction of TP53 was lower in LAMN compared with those of other tumors. The Ki-67 labeling index was slightly lower in LAMN than those in other tumors. The recurrence and death in LAMN is infrequent compared with those in AC and MAC. CONCLUSIONS: The current study suggested the impairment of DDR in AC and MAC. DDR appeared to be preserved in LAMN, and it may account for low proliferating activity and a favorable clinical course in LAMN.
BACKGROUND:Appendiceal tumors are rare, and their pathogenesis is not well known. DNA damage response (DDR) is a sequence from the detection of damaged DNA to the repair, and its impairment is implicated in the progression of cancers. The aim of the current study is to explore the expression and phosphorylation of checkpoint kinase 2 (Chk2) and TP53, which are key molecules in DDR, and their clinicopathological correlation in the appendiceal tumors. METHODS:Chk2, phosphorylated Chk2 (pChk2), and TP53 were immunostained in 4 cases of adenoma (AD), 5 non-mucinous adenocarcinomas (AC), 29 low-grade appendiceal mucinous neoplasms (LAMN), and 7 mucinous adenocarcinomas (MAC). Ki-67 labeling index was also evaluated by immunostaining. RESULTS:Chk2 was highly expressed in the nuclei of all the appendiceal tumors. While pChk2 was high in AD, LAMN, and MAC, it was reduced in AC. Nuclear positive reaction of TP53 was lower in LAMN compared with those of other tumors. The Ki-67 labeling index was slightly lower in LAMN than those in other tumors. The recurrence and death in LAMN is infrequent compared with those in AC and MAC. CONCLUSIONS: The current study suggested the impairment of DDR in AC and MAC. DDR appeared to be preserved in LAMN, and it may account for low proliferating activity and a favorable clinical course in LAMN.
Authors: J M Cunningham; C Y Kim; E R Christensen; D J Tester; Y Parc; L J Burgart; K C Halling; S K McDonnell; D J Schaid; C Walsh Vockley; V Kubly; H Nelson; V V Michels; S N Thibodeau Journal: Am J Hum Genet Date: 2001-08-24 Impact factor: 11.025
Authors: Joseph Misdraji; Rhonda K Yantiss; Fiona M Graeme-Cook; Ulysses J Balis; Robert H Young Journal: Am J Surg Pathol Date: 2003-08 Impact factor: 6.394
Authors: Melissa W Taggart; John Galbincea; Paul F Mansfield; Keith F Fournier; Richard E Royal; Michael J Overman; Asif Rashid; Susan C Abraham Journal: Am J Surg Pathol Date: 2013-08 Impact factor: 6.394
Authors: Moritz Komm; Michaela Kronawitter-Fesl; Marcus Kremer; Ludwig Lutz; Elke Holinski-Feder; Reinhard Kopp Journal: J Cancer Date: 2011-05-23 Impact factor: 4.207