Jedpiyawongse Adisorn, Homcha-em Patcharin, Karalak Anant, Srivatanakul Petcharin
National Cancer Institute, Department of Medical Services, Bangkok, Thailand.
Asian Pac J Cancer Prev. 2008 Oct-Dec;9(4):625-30.
Cervical cancer is caused by persistent infections through high risk (HR) types of human HPVs, particularly HPV 16 and 18. HR-HPV types encode two potent oncogenes, referred to as E6 and E7. Both are required to induce and maintain neoplastic growth of cervical cancer cells. Cyclin dependent kinase inhibitor genes as for example p16INK4A were shown to be negative regulated by active pRb. Inactivation of pRb by E7 thus releases the p16 gene from its negative transcriptional control and results in significant overexpression of p16 encoded protein in HPV transformed cells. It has been demonstrated that p16 protein can be detected in cervical preneoplasia all high grade SIL or invasive cancers, whereas no expression was detected in normal, metaplastic or inflammatory cervical lesions. Moreover, low grade cervical lesions induced by low risk HPV infection but histological indistinguishable from low grade lesions induced by HR-HPV-infections could be clearly differentiated by p16INK4A immunohistochemistry, showing negative staining for p16 protein. The objective of this study is to examine the expression of p16 protein in cervical carcinoma in Thailand. Immunohistochemical analysis of p16INK4A was performed on 53 formalin fixed and paraffin embedded samples of various stages of cervical neoplastic lesions. There are squamous cell carcinoma in situ 8 cases, squamous cell carcinoma in situ with glandular involvement 16 cases, microinvasive squamous cell carcinoma 13 cases and invasive squamous cell carcinoma 16 cases. The specimens were taken from cervical biopsy, cervical conization and hysterectomy in the year 2000 at National Cancer Institute. Strong immunoreactivity for the p16 protein was observed in only the nuclei and cytoplasm of all cervical neoplastic cells. This study supported the idea that immunohistochemical overexpression of the p16 protein may be a useful screening test for cervical cancer. In addition, p16 immunohistochemistry is useful for helping in the interpretation of cervical histology samples, facilitating more rapid diagnosis.
宫颈癌是由高危（HR）型人乳头瘤病毒（HPV）的持续感染引起的，尤其是HPV 16和18型。HR-HPV型编码两种有效的致癌基因，即E6和E7。两者都是诱导和维持宫颈癌细胞肿瘤生长所必需的。细胞周期蛋白依赖性激酶抑制剂基因，例如p16INK4A，已被证明受到活性pRb的负调控。E7使pRb失活，从而使p16基因从其负转录控制中释放出来，导致HPV转化细胞中p16编码蛋白的显著过表达。已经证明，在宫颈瘤前病变、所有高级别鳞状上皮内病变（SIL）或浸润性癌中都可以检测到p16蛋白，而在正常、化生或炎性宫颈病变中未检测到表达。此外，低风险HPV感染引起的低级别宫颈病变，但在组织学上与HR-HPV感染引起的低级别病变无法区分，可以通过p16INK4A免疫组织化学清楚地区分，显示p16蛋白染色阴性。本研究的目的是检测泰国宫颈癌中p16蛋白的表达。对53例福尔马林固定石蜡包埋的不同阶段宫颈肿瘤病变样本进行了p16INK4A的免疫组织化学分析。其中原位鳞状细胞癌8例，原位鳞状细胞癌伴腺体受累16例，微浸润鳞状细胞癌13例，浸润性鳞状细胞癌16例。标本取自2000年国家癌症研究所的宫颈活检、宫颈锥切术和子宫切除术。仅在所有宫颈肿瘤细胞的细胞核和细胞质中观察到p16蛋白的强免疫反应性。本研究支持这样的观点，即p16蛋白的免疫组织化学过表达可能是一种有用的宫颈癌筛查试验。此外，p16免疫组织化学有助于宫颈组织学样本的解读，便于更快地做出诊断。
