Qiao Xiaoying, Bhuiya Tawfiqul A, Spitzer Mark
Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, New York, USA.
J Low Genit Tract Dis. 2005 Apr;9(2):100-7. doi: 10.1097/00128360-200504000-00006.
In postmenopausal women, differentiating high-grade cervical intraepithelial neoplasia (CIN 2,3) from atrophic uterine cervical squamous epithelium histologically may pose a diagnostic challenge. Recent studies have indicated the value of using a combination of Ki-67, cyclin E, and p16 immunohistochemical analysis in recognizing CIN 2,3. In this study, we compared the staining features of Ki-67, cyclin E, and p16 in cervix specimens from postmenopausal women to distinguish CIN 2,3 from atrophy.
Twenty-six formalin-fixed paraffin-embedded archival cervical specimens (4 biopsy, 8 laser cone, and 14 total hysterectomy samples) were selected from 25 women 50 to 80 years of age (mean = 64 years). Cases included CIN 2,3 (n = 10), atrophy (n = 9), and coexistent CIN 2,3 and atrophy (n = 6). Slides were stained with monoclonal antibodies to Ki-67, cyclin E, and p16 using the avidin-biotin-peroxidase method. Strength of staining was graded as 1+ to 3+. Pattern of staining was described as diffuse, patchy, or scattered. Ki-67 staining restricted to the basal/parabasal zone was scored as negative.
All CIN 2,3 cases demonstrated variable positivity for Ki-67, cyclin E, and p16. Most CIN 2,3 cases showed strong p16 (81.3%) and Ki-67 (75.0%) reactivity, while only 31.3% of them showed strong cyclin E activity. Some CIN 2,3 cases demonstrated strong p16 but weak Ki-61 and cyclin E reactivity. All atrophic epithelia were negative for p16, cyclin E, and Ki-67. In coexistent CIN 2,3 and atrophy cases, the three-antibody panel clearly demarcated the transition from benign to neoplastic epithelia.
P16 is the most valuable marker followed by Ki-67 for differentiating CIN 2,3. While cyclin E appears to add limited value on these two markers. Therefore, although the three-antibody immunohistochemical panel (p16, Ki-67, and cyclin E) can be a valuable adjunct to routine hematoxylin-eosin staining, it is also possible to use the two-antibody panel (p16 and Ki-67) to effectively distinguish CIN 2,3 from atrophy in postmenopausal women.
在绝经后女性中，从组织学上鉴别高级别宫颈上皮内瘤变（CIN 2、3）与萎缩性子宫颈鳞状上皮可能是一项诊断挑战。最近的研究表明，联合使用Ki-67、细胞周期蛋白E和p16免疫组化分析在识别CIN 2、3方面具有价值。在本研究中，我们比较了绝经后女性宫颈标本中Ki-67、细胞周期蛋白E和p16的染色特征，以区分CIN 2、3与萎缩。
从25名年龄在50至80岁（平均64岁）的女性中选取26份福尔马林固定石蜡包埋的宫颈存档标本（4份活检标本、8份激光锥切标本和14份全子宫切除标本）。病例包括CIN 2、3（n = 10）、萎缩（n = 9）以及CIN 2、3与萎缩并存（n = 6）。使用抗生物素蛋白-生物素-过氧化物酶方法，用针对Ki-67、细胞周期蛋白E和p16的单克隆抗体对玻片进行染色。染色强度分为1+至3+。染色模式描述为弥漫性、斑片状或散在性。局限于基底/副基底区的Ki-67染色计为阴性。
所有CIN 2、3病例的Ki-67、细胞周期蛋白E和p16均表现出不同程度的阳性。大多数CIN 2、3病例显示p16（81.3%）和Ki-67（75.0%）反应性强，而只有31.3%的病例显示细胞周期蛋白E活性强些。一些CIN 2、3病例显示p16强阳性，但Ki-61和细胞周期蛋白E反应性弱。所有萎缩性上皮的p16、细胞周期蛋白E和Ki-67均为阴性。在CIN 2、3与萎缩并存的病例中，三联抗体组清晰地划分了从良性上皮到肿瘤性上皮的转变。
对于鉴别CIN 2、3，p16是最有价值的标志物，其次是Ki-67。而细胞周期蛋白E在这两种标志物的基础上似乎增加的价值有限。因此，尽管三联抗体免疫组化组（p16、Ki-67和细胞周期蛋白E）可作为常规苏木精-伊红染色的有价值辅助手段，但也可以使用二联抗体组（p16和Ki-67）来有效区分绝经后女性的CIN 2、3与萎缩。
