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p16INK4a、细胞角蛋白 7 和 Ki-67 作为低级别宫颈上皮内瘤变进展的潜在标志物。

p16INK4a, Cytokeratin 7, and Ki-67 as Potential Markers for Low-Grade Cervical Intraepithelial Neoplasia Progression.

机构信息

Department of Pathology, Faculty of Medical Sciences, Universidade Estadual de Campinas (Unicamp), Campinas, São Paulo, Brazil.

出版信息

J Low Genit Tract Dis. 2017 Jul;21(3):171-176. doi: 10.1097/LGT.0000000000000310.

DOI:10.1097/LGT.0000000000000310
PMID:28403025
Abstract

OBJECTIVE

The aim of this study was to evaluate p16, cytokeratin 7 (CK7), and Ki-67 immunoexpressions in low-grade squamous intraepithelial lesion (LSIL), looking for differences among cases that progress to high-grade squamous intraepithelial lesion, maintain LSIL, or regress.

MATERIALS AND METHODS

Sixty-six LSIL biopsies were studied. In the follow-up, a second biopsy showed 28.7% regression, 37.9% LSIL, and 33.4% progressed to high-grade squamous intraepithelial lesion. Immunostaining for these markers were performed in the first biopsy. A qualitative evaluation method was used, as well as histomorphometry, using ImageJ software. Pearson χ, Mann-Whitney, Kruskal-Wallis, and Fisher tests were used to compare the groups (P ≤ .05). A cutoff point was assessed through receiver operating characteristic curve positive cell ratio, for each marker, as progression predictors.

RESULTS

The mean age of patients with and without progression was 33 and 27 years (P = .006), respectively. The qualitative evaluation indicated a tendency of progression, but without statistical significance. However, through histomorphometry, the receiver operating characteristic curve analysis showed cutoff points of 0.396, 0.345, and 0.026 for p16, CK7, and Ki-67 ratios, respectively, as predictors of progression (P = .003, .03, and .002, respectively). In a logistic regression analysis, p16, CK7, and Ki-67 positive cell ratio showed a significant correlation with progression (P = .036, .012, and .006, respectively).

CONCLUSIONS

p16, CK7, and Ki-67 may represent useful biomarkers that can identify LSIL lesions that need particular attention.

摘要

目的

本研究旨在评估低级别鳞状上皮内病变(LSIL)中 p16、细胞角蛋白 7(CK7)和 Ki-67 的免疫表达,寻找进展为高级别鳞状上皮内病变、维持 LSIL 或消退的病例之间的差异。

材料和方法

研究了 66 例 LSIL 活检。在随访中,第二次活检显示 28.7%消退、37.9% LSIL 和 33.4%进展为高级别鳞状上皮内病变。在第一次活检中进行了这些标志物的免疫染色。使用定性评估方法和 ImageJ 软件进行组织形态计量学分析。使用 Pearson χ²、Mann-Whitney、Kruskal-Wallis 和 Fisher 检验比较各组(P ≤.05)。通过受试者工作特征曲线评估每个标志物的阳性细胞比例作为进展预测的截断点。

结果

有进展和无进展患者的平均年龄分别为 33 岁和 27 岁(P =.006)。定性评估表明存在进展趋势,但无统计学意义。然而,通过组织形态计量学分析,受试者工作特征曲线分析显示 p16、CK7 和 Ki-67 比值的截断点分别为 0.396、0.345 和 0.026,可作为进展预测指标(P =.003、.03 和.002,分别)。在逻辑回归分析中,p16、CK7 和 Ki-67 阳性细胞比例与进展呈显著相关(P =.036、.012 和.006,分别)。

结论

p16、CK7 和 Ki-67 可能是有用的生物标志物,可以识别需要特别关注的 LSIL 病变。

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