The pattern of p14ARF expression in primary and metastatic human endometrial carcinomas: correlation with clinicopathological features and TP53 pathway alterations.

Objectives: Alterations of p53 pathway (p14(ARF)/MDM2/p53) play a crucial role in the development and progression of various human neoplasms, including endometrial carcinoma (EC). The aim of the current research was to examine the p14(ARF) expression pattern in primary ECs and corresponding metastatic lesions.

Materials And Methods: We studied 47 primary ECs and corresponding metastatic lesions applying immunohistochemistry and investigated the relationship between p14(ARF) overexpression and clinicopathological variables of carcinoma as well as TP53 alterations.

Results: Protein expression was predominantly nuclear, present in 32 (68%) of 47 primary cases and in 28 (60%) of 47 metastatic lesions. There were seven p14(ARF)-positive primary tumors showing negative reactivity in the metastatic lesions. On the other hand, 3 cases lacked protein immunoreactivity in the primary ECs but revealed weak nuclear staining in the corresponding metastases. A case of primary cervical adenocarcinoma metastasizing to the lymph nodes showed p14(ARF) expression both in the primary tumor and the corresponding metastases. A trend was found between the p14(ARF) expression in primary tumors and the presence of the neoplasms in the fallopian tube (P = 0.063), but none of the other clinicopathological variables of carcinoma was related to protein immunoreactivity in advanced-stage uterine neoplasms. The p14(ARF) expression in EC metastases was related to the presence of the primary tumor in the fallopian tube (P = 0.036). The p14(ARF) expression was not associated with unfavorable outcome both in the primary tumors (P = 0.302) and in the corresponding metastases (P = 0.217). There was also no relationship between the p14(ARF) expression pattern and TP53 pathway alterations.

Conclusions: Altogether, the p14(ARF) protein is expressed in more than half of the primary ECs and metastatic lesions analyzed and is associated with the transtubal dissemination of the primary tumor. The pattern of the p14(ARF) expression is not associated with the alterations of other TP53 pathway members in advanced-stage human ECs.