Laboratory of Cytogenetic and Reproductive Biology, Hospital Aristide-Le-Dantec, Pasteur Avenue, Dakar, Senegal.
Laboratory of Anatomy and Pathology, Principal Military Hospital of Dakar, Nelson Mandela Avenue, Dakar, Senegal.
Asian Pac J Cancer Prev. 2020 Nov 1;21(11):3221-3227. doi: 10.31557/APJCP.2020.21.11.3221.
Cervical intraepithelial neoplasia (CIN) grading is subjective and affected by substantial rates of discordance among pathologists. Although recent studies have suggested that p16INK4a may be a useful surrogate biomarker of cervical neoplasia, Ki-67 and human papillomavirus testing have also been shown to be useful in detecting neoplasia. The purpose of this study was to determine the expression of p16INK4a and Ki-67 in cervical neoplasia and its correlations with cofactors.
The study involved 69 patients with and without cervical neoplasia who underwent colposcopic directed biopsy. On each patient, two samples were taken; the first was used for immunohistochemistry and the second for molecular testing, using HPV16and18 genotyping Real-Time PCR Kit.
The study revealed the expression level of p16INK4a and Ki-67 in a descending order, from invasive squamous cell carcinoma (SCC), CIN2/3, CIN1 and non-dysplastic lesions. Correlations showed an association between the staining of p16NK4a and Ki-67 with the increase of age (OR: 1.79 (95%IC: 0.49 - 6.55), p = 0.037) and marital status (OR: 0.17 (95%IC: 0.04 - 0.68), p = 0.003). We found that the expressions of p16INK4a and Ki-67 were significantly different between invasive SCC vs non-dysplasia (OR: 44.57 (95%IC: 4.91 - 403.91), p <0.0001). The study showed significant correlation between HPV 16and18 infection with p16 INK4a and Ki-67 expression (OR: 0.13 (95%IC: 0.03 - 0.52), p <0.0001). Strong expression of p16INK4a and Ki-67 were observed in invasive squamous cell carcinoma, moderate staining was found in CIN2/3, weak staining in CIN1 and normal histology.
Our findings indicate that p16INK4a and Ki-67 expressions associated strongly with cervical pathology. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.
宫颈上皮内瘤变（CIN）分级具有主观性，并且受到病理学家之间存在大量不一致的影响。尽管最近的研究表明，p16INK4a 可能是宫颈癌的有用替代生物标志物，但 Ki-67 和人乳头瘤病毒（HPV）检测也已被证明可用于检测肿瘤。本研究旨在确定 p16INK4a 和 Ki-67 在宫颈癌中的表达及其与伴随因素的相关性。
本研究纳入了 69 例患有和未患有宫颈癌的患者，这些患者均接受了阴道镜指导下的活检。对每位患者采集两份样本；第一份用于免疫组织化学，第二份用于分子检测，使用 HPV16 和 18 基因分型实时 PCR 试剂盒。
研究结果显示，p16INK4a 和 Ki-67 的表达水平呈递减顺序，从浸润性鳞状细胞癌（SCC）、CIN2/3、CIN1 和非发育不良病变。相关性分析显示，p16NK4a 和 Ki-67 的染色与年龄（比值比：1.79（95%置信区间：0.49-6.55），p=0.037）和婚姻状况（比值比：0.17（95%置信区间：0.04-0.68），p=0.003）有关。我们发现，p16INK4a 和 Ki-67 的表达在浸润性 SCC 与非发育不良病变之间存在显著差异（比值比：44.57（95%置信区间：4.91-403.91），p<0.0001）。研究表明，HPV16 和 18 感染与 p16INK4a 和 Ki-67 的表达呈显著相关（比值比：0.13（95%置信区间：0.03-0.52），p<0.0001）。在浸润性鳞状细胞癌中观察到 p16INK4a 和 Ki-67 的强表达，在 CIN2/3 中观察到中度染色，在 CIN1 和正常组织学中观察到弱阳性染色。
我们的研究结果表明，p16INK4a 和 Ki-67 的表达与宫颈病变密切相关。因此，p16/Ki-67 可以被视为宫颈癌筛查的合适生物标志物，尤其是在 HPV 为基础的筛查方案中。
