Identification of human papillomavirus and Rb/E2F pathway genomic alterations in mixed adeno-neuroendocrine carcinoma.

OBJECTIVE

To investigate the molecular characteristics of Rb/E2F in mixed adeno-neuroendocrine carcinoma (MANEC).

MATERIALS AND METHODS

The clinicopathological features of MANEC were analyzed. The protein expressions of Rb, p16, and p53 were detected by the immunohistochemical method. The infection status of high-risk human papillomavirus (HR-HPV) was evaluated by in situ hybridization (ISH) and the gene chip method.

RESULTS

Thirteen cases of MANEC were divided into four molecular patterns according to Rb protein expression and HPV status. Group 1: A total of eight of the 13 cases showed positive Rb protein expression and lack of HR-HPV expression (8/13, 62%). Rb protein expression with p16 protein deletion and p53 protein abnormal expression was unique to NEC. Group 2: three cases (3/13, 23%) with negative Rb protein expression and lack of HR-HPV expression. Group 3: There was one case (1/13, 8%) with positive expression of Rb protein accompanied by HR-HPV. Group 4: There was one case of Rb protein loss with an HR-HPV-positive status.

CONCLUSIONS

HR-HPV and Rb/p16/p53 pathway can be associated in MANEC pathogenesis, which provides the research basis for personalized treatment of MANEC.