Stromal p16 Overexpression in Gastric-type Mucinous Carcinoma of the Uterine Cervix

Background/Aim: Gastric-type mucinous carcinoma (MC-G) of the uterine cervix displays distinct morphological features and an aggressive clinical course. The expression status of p16 in the stroma has not been investigated in adenocarcinoma of the uterine cervix. Stromal p16 expression was evaluated in endocervical adenocarcinomas, including usual-type endocervical adenocarcinoma (UEA), intestinal-type mucinous carcinoma (MC-I), and MC-G. Whether stromal p16 expression varied significantly according to the histological subtype and whether the expression status is associated with clinicopathological characteristics of MC-G was also investigated. Materials and Methods: Immunostaining of p16 was performed for 24, 19, and 18 cases of UEA, MC-I, and MC-G, respectively. Results: UEA and MC-I subtypes exhibited horizontally continuous, strong nuclear p16 immunoreactivity in the tumor cells, whereas none of the MC-G cases showed diffuse and strong nuclear immunoreactivity for p16 in the tumor cells. Instead, 10 (55.6%) cases of MC-G displayed moderately to strongly positive p16 expression in the stroma. Stromal p16 expression of MC-G was significantly higher than that of normal cervix, UEA, and MC-I. Metastatic MC-G had significantly higher stromal p16 expression than primary MC-G. Further, stromal p16 overexpression in MC-G was associated with advanced stage, parametrial invasion, and lymphovascular invasion. Conclusion: Stromal p16 expression of MC-G was significantly higher than that of normal cervix and other histological subtypes of adenocarcinoma and was associated with advanced stage, parametrial invasion, and lymphovascular invasion, reflecting the aggressive behavior of MC-G. Our observations suggest that stromal p16 expression is involved in the development and progression of MC-G.