HPV阴性的宫颈癌和癌前病变中p14ARF蛋白表达及其临床意义

Expression and clinical significance of p14ARF protein in HPV-negative patients with cervical cancer and cervical precancerous lesion

目的:通过检测人乳头状瘤病毒(HPV)感染阴性的宫颈癌和宫颈上皮内瘤变中p14ARF和基质金属蛋白酶MMPs及其抑制物TIMPs的表达,探讨其与宫颈癌早期诊断、侵袭转移的关系。方法:以PCR方法筛查HPV阴性的慢性宫颈炎30例、宫颈上皮内瘤变(CIN)35例及宫颈浸润癌35例作为研究对象,采用SP染色法检测p14ARF蛋白在其中的表达,分析p14ARF蛋白在宫颈癌组织中的表达、临床病理特征及其与浸润深度、淋巴结转移的相关性。结果:p14ARF蛋白特异性表达在HPV阴性的CIN病变、宫颈癌细胞核及胞质中,在正常鳞状上皮和腺上皮中无任何阳性表达信号,且与临床分期无关,与细胞分化程度、淋巴结转移有关。结论:p14ARF蛋白检测可作为HPV阴性宫颈癌的早期诊断指标,并可作为预测宫颈癌侵袭转移潜能和临床预后的指标。

Objective：To explore the relationship between p14ARF protein,matrix metalloproteinases（MMPs）,tissue inhibitors of metalloproteinases（TIMPs） and early diagnosis,invasion and metastasis of cervical cancer by detecting their expression levels in cervical cancer and cervical intraepithelial neoplasia（CIN） of human papillomavirus（HPV）-negative patients.Methods：30 HPV-negative patients with chronic cervicitis,35 HPV-negative patients with CIN and 35 HPV-negative patients with cervical invasive cancer were selected as study objects by PCR.Immunohistochemical SP staining was used to detect the expression level of p14ARF protein,clinicopathological characteristics and the correlation with the depth of invasion and lymph node metastasis.Results：P14ARF protein specifically expressed in the nuclei and cytoplasm of CIN and cervical cancer cells,and it never expressed in normal squamous epithelium and glandular epithelium,there was no correlation between P14ARF protein expression and clinical stages,while it was related to the degree of differentiation and lymph node metastasis.Conclusion：p14ARF protein detection can be used as an index for early diagnosis of cervical cancer among HPV-negative patients,which also can be used as an index to predict the potential of invasion and metastasis of cervical cancer and clinical prognosis.