DNA damage response and its clinicopathological relationship in appendiceal tumors

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Appendiceal tumors are rare with poorly understood pathogenesis.
• DNA damage response (DDR) is crucial for cancer progression, and its impairment is linked to cancer development.
• Checkpoint kinase 2 (Chk2) and TP53 are key DDR molecules.

Purpose of the Study:

• To investigate the expression and phosphorylation of Chk2 and TP53 in appendiceal tumors.
• To correlate DDR molecule status with clinicopathological features of appendiceal tumors.

Main Methods:

• Immunohistochemical staining for Chk2, phosphorylated Chk2 (pChk2), and TP53 in appendiceal adenoma (AD), non-mucinous adenocarcinoma (AC), low-grade appendiceal mucinous neoplasm (LAMN), and mucinous adenocarcinoma (MAC).
• Evaluation of Ki-67 labeling index.
• Correlation with clinical outcomes such as recurrence and death.

Main Results:

• Chk2 was highly expressed in all appendiceal tumors.
• pChk2 levels were high in AD, LAMN, and MAC but reduced in AC.
• TP53 nuclear expression was lower in LAMN compared to other tumors; Ki-67 index was also lower in LAMN.
• LAMN showed infrequent recurrence and death compared to AC and MAC.

Conclusions:

• DDR is impaired in appendiceal adenocarcinomas (AC) and mucinous adenocarcinomas (MAC).
• DDR appears preserved in low-grade appendiceal mucinous neoplasms (LAMN).
• Preserved DDR in LAMN may explain its low proliferation and favorable clinical course.