高危型人乳头状瘤病毒DNA检测及p16INK4A蛋白表达在子宫颈腺癌诊断中的意义

目的观察p16^INK4A（简称p16）蛋白在子宫颈腺癌和子宫内膜腺癌中的表达及其和高危型人乳头状瘤病毒DNA（HPVDNA）在这两种腺癌中的鉴别诊断价值。方法用免疫组织化学EliVision法检测30例子宫颈腺癌和10例子宫内膜腺癌中p16蛋白的表达情况;并用原位杂交法检测20例子宫颈腺癌和10例子宫内膜腺癌中HPVDNA。结果在30例子宫颈腺癌中21例p16蛋白阳性（70％）,而10例子宫内膜腺癌中3例为阳性。在子宫颈腺癌中p16蛋白呈弥漫性细胞核和细胞质阳性,在子宫内膜腺癌中呈不规则斑点状阳性表达,而且总体强度较弱。HPv16和18在20例子宫颈腺癌中9例（45％）阳性,即细胞核内观察到点状棕黄色颗粒。10例子宫内膜腺癌均为阴性。结论鉴于p16蛋白的表达模式比HPV DNA的检测敏感性高,且易于操作,故建议将其作为区分宫颈癌和子宫内膜腺癌的辅助指标,特别是在活检或诊刮时应增加p16蛋白和HPV DNA的检测。

Role of HPV DNA detection and p16(INK4A) protein expression in diagnosis of endocervical adenocarcinoma

OBJECTIVES: To evaluate the significance of p16(INK4A) protein expression and positivity for HPV DNA in distinguishing between endocervical and endometrial adenocarcinoma. METHODS: Expression of p16(INK4A) protein in 30 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma was assessed by immunohistochemistry. In-situ hybridization for human papillomavirus (HPV) DNA was also performed in 20 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma. RESULTS: The positive rate for p16(INK4A) in endocervical adenocarcinoma was 70% (21/30), as compared with 30% (3/10) in endometrial adenocarcinoma. The tumor cells in endocervical adenocarcinoma showed diffuse and strong expression of p16(INK4A) protein with both cytoplasmic and nuclear staining. In contrast, the endometrial adenocarcinoma cells showed patchy and weak expression of p16(INK4A). On the other hand, HPV DNA (type 16 or 18) was detected by in-situ hybridization in 9 (45%) of the 20 cases of endocervical adenocarcinoma and none of the 10 cases of endometrial adenocarcinoma. CONCLUSIONS: The expression of p16(INK4A) protein is significantly higher in endocervical adenocarcinoma than in endometrial adenocarcinoma. This expression pattern can serve as a useful immunohistochemical marker in the differential diagnosis. p16(INK4A) protein immunohistochemistry appears to be more sensitive than HPV DNA testing in distinguishing between endocervical and endometrial adenocarcinoma, especially in biopsy or curettage specimens.