Department of Pathology, Brigham and Women's Hospital, Division of Women's and Perinatal Pathology, Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston, MA, USA.
Am J Surg Pathol. 2013 May;37(5):625-33. doi: 10.1097/PAS.0b013e318285be00.
Conventional endocervical adenocarcinoma in situ (cAIS) is typically strongly and diffusely positive for p16 with a high Ki67 index consistent with its frequent association with high-risk human papillomavirus (HPV) infection. The intestinal variant (iAIS) is less common, and its relationship to HPV infection has not been thoroughly examined. This study compares the clinicopathologic features, frequency of HPV infection, and expression of CDX2 and surrogate biomarkers of HPV infection (p16, Ki67) in cAIS with those of iAIS. A total of 86 cases with a diagnosis of AIS (49 iAIS, 37 cAIS) were identified from our multi-institutional files. Of these, 13 iAIS and 20 cAIS cases had slides and tissue available for histopathologic review, immunohistochemical analysis, and molecular tests. All 86 cases were used to evaluate clinical parameters; however, HPV DNA analysis and immunohistochemical analysis for p16, MIB-1, CDX2, and p53 were performed only on those cases with available slides or paraffin blocks. The average age at diagnosis was significantly higher in iAIS compared with that in cAIS (44.5 vs. 32.6 y) (P=0.0001). All 20 cAIS cases showed moderate to strong and diffuse p16 staining; however, only 9/13 iAIS cases showed this degree of p16 staining, whereas 4/13 (31%) iAIS cases showed weak and patchy distribution (P<0.02). Only 6/9 (67%) iAIS cases were positive for either HPV type 18 (5) or 33 (1), in contrast to 11/11 conventional cAIS (P=0.04). Similarly, 12/14 cAIS, but only 5/13 iAIS, cases showed a high Ki67 proliferative index. CDX2 was positive in all iAIS cases, whereas p53 was negative. Most iAIS cases are positive for high-risk HPV and show moderate to strong and diffuse p16 staining; however, a subset of iAIS shows variable staining with p16 and Ki67, is not associated with HPV, and occurs in a distinctly older age group suggesting an alternative pathogenesis. Awareness that iAIS can show variable staining for p16 and Ki67 is important when resolving problematic endocervical lesions, particularly in small biopsies with unusual p16 staining patterns.
传统的宫颈管内腺癌原位（cAIS）通常强烈且弥漫性地表达 p16，Ki67 指数较高，这与其常与高危型人乳头瘤病毒（HPV）感染有关。肠型（iAIS）较为少见，其与 HPV 感染的关系尚未得到充分研究。本研究比较了 cAIS 和 iAIS 的临床病理特征、HPV 感染频率以及 CDX2 和 HPV 感染替代标志物（p16、Ki67）的表达。从我们的多机构档案中确定了 86 例 AIS 病例（49 例 iAIS，37 例 cAIS）。其中，13 例 iAIS 和 20 例 cAIS 病例有可供组织病理学复查、免疫组织化学分析和分子检测的切片和组织。所有 86 例病例均用于评估临床参数；然而，仅对有可用切片或石蜡块的病例进行 HPV DNA 分析和 p16、MIB-1、CDX2 和 p53 的免疫组织化学分析。iAIS 的平均发病年龄明显高于 cAIS（44.5 岁 vs. 32.6 岁）（P=0.0001）。所有 20 例 cAIS 病例均显示中度至强和弥漫性 p16 染色；然而，仅有 9/13 例 iAIS 病例显示这种程度的 p16 染色，而 4/13（31%）例 iAIS 病例显示弱阳性和斑片状分布（P<0.02）。仅 6/9（67%）例 iAIS 病例呈 HPV 型 18（5 例）或 33（1 例）阳性，而传统 cAIS 中 11/11 例阳性（P=0.04）。同样，12/14 例 cAIS 病例，但仅 5/13 例 iAIS 病例，Ki67 增殖指数较高。所有 iAIS 病例 CDX2 阳性，而 p53 阴性。大多数 iAIS 病例呈高危型 HPV 阳性，且 p16 染色呈中度至强和弥漫性；然而，一部分 iAIS 病例的 p16 和 Ki67 染色存在差异，与 HPV 无关，且发生在年龄明显较大的年龄组，提示存在不同的发病机制。当解决有问题的宫颈内病变，特别是在具有不典型 p16 染色模式的小活检中时，认识到 iAIS 可能存在不同的 p16 和 Ki67 染色模式非常重要。
