The use of p16INK4A immunocytochemistry in “Atypical squamous cells which cannot exclude HSIL” compared with “Atypical squamous cells of undetermined significance” in liquid‐based cervical smears

Even though p16^INK4a (p16) immunocytochemistry has proven a useful accessory tool verifying the identification of atypical squamous cells of undetermined significance (ASC‐US) categorized smears, the procedure still has limitations. To date few studies examining the usefulness of p16 immunocytochemistry in atypical squamous cells which cannot exclude HSIL (ASC‐H), compared with ASC‐US in liquid‐based cervical smears. Therefore, we examined the correlation of p16 immunocytochemical staining with follow‐up biopsy results on ASC‐H categorized smears and compared the data with those classified as ASC‐US on 105 liquid‐based cytology samples. We found no statistical significance in the p16 expression of ASC‐US smears and the presence of squamous intraepithelial lesions (SIL) in follow‐up biopsies (p = 0.546). However, p16 expression did significantly correlate with the presence of SIL (p = 0.002) in ASC‐H smears. There was a statistically significant relationship between p16 expression and presence of high grade squamous intraepithelial lesions (HSIL) or more on the follow‐up biopsies in both ASC‐US (p = 0.012) and ASC‐H (p < 0.001) categorized smears. In ASC‐US categorized smears, there was no statistical significance between p16 expression and the HR‐HPV viral load (p = 0.091). But there was a statistical significance between p16 expression and the HR‐HPV viral load (p < 0.001) in ASC‐H categorized smears. Our results indicate that p16 immunostaining is a much better useful marker for HR‐HPV infection and detection of SIL in ASC‐H categorized smears compared to those defined as ASC‐US. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

An analysis on the combination expression of HPV L1 capsid protein and p16INK4a in cervical lesions

Human papillomavirus (HPV) infection in cervix is the most important reason for cervical cancer, but only 2% cervical HPV infection will develop into cervical cancer. So how to identify patients at risk of progressive cervical lesions from those infected with HPV to avoid over treatment is a big issue in clinic. The aims of this study were to detect the expression of HPV L1 capsid protein and p16^INK4a in cervical lesions and to investigate the combination expression of HPV L1 capsid protein and p16^INK4a in cervical lesions and its diagnostic efficiency in clinic. Immunochemical method was used to detect the expression of HPV L1 capsid protein and p16^INK4a in 169 cases of abnormal cytology. Histopathologic test was performed to identify cervical lesions of all the cases. χ² test and spearman's rank correlation were used for statistical analysis. The diagnostic sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), accuracy, and the area under the receive operating characteristic (ROC) curve (denoted by A_Z) were calculated with SPSS 13.0. All the statistical tests were two sided at the 5% level of significance. L1 expression decreased (P < 0.001), but p16^INK4a expression increased (P < 0.001) with histopathologic diagnosis increasing. The expression rates of HPV L1 capsid protein, p16^INK4a, and L1(?)/p16(+) in cervical intraepithelial neoplasia (CIN)2, CIN3, and squamous‐cell carcinoma were statistically different from those in CIN1 (P < 0.001). The expressions of HPV L1 capsid protein, L1(+)/p16(+), L1(+)/p16(?), and L1(?)/p16(?) were negatively correlated with the severity of cervical lesions (P < 0.001), whereas the expressions of p16^INK4a and L1(?)/p16(+) were positively correlated with the severity of cervical lesions (P < 0.001). The specificity and A_Z of combining L1 with p16 ^INK4a were statistically higher than L1 or p16 ^INK4a alone (P < 0.05). L1 and p16^INK4a are useful biomarkers for the early diagnosis of cervical lesions. The combination of L1 and p16^INK4a has a higher diagnostic accuracy than L1 or p16^INK4a alone in diagnosis of cervical lesions. Diagn. Cytopathol. 2010;38:573–578. © 2009 Wiley‐Liss, Inc.     

Telomerase activity, MIB-1, PCNA, HPV 16 and p53 as diagnostic markers for cervical intraepithelial neoplasia

The present investigation evaluated the relationship between dysplasia of the uterine cervix and telomerase activity, expression of p53, MIB-1 and PCNA. Telomerase activity was measured on cervical cytobrush material from 126 women suspected of having dysplasia and 61 controls using the telomeric repeat amplification protocol. Immunohistochemistry was used to detect the tumor suppressor protein p53 and cell proliferation, the latter by MIB-1 and PCNA expression. Infection with human papillomavirus 16 was detected by PCR amplification and Southern blot hybridization of DNA extracted from the same brush material. Positive telomerase activity was found in 5 of 43 (11.6%) normal samples, 12 of 57 (21.1%) samples with inflammation or koilocytosis, 7 of 17 (41.2%) CIN 1 (cervical intraepithelial neoplasia, grade 1), 8 of 20 (40.0%) CIN 2, and 25 of 42 (59.5%) CIN 3/ CIS. Telomerase activity was significantly related to the level of dysplasia (p<0.001) and proliferation measured by MIB-1 (p=0.019), but not to the level of PCNA (p=0.445), HPV 16 status (p=0.098) or staining for p53 (p=0.271). Dysplasia was also related to PCNA, MIB1, p53, and presence of HPV 16. A sequential increase in the examined parameters, paralleling the progression of abnormality, was observed. PCNA and telomerase showed an increase in CIN 1, MIB-1 and HPV16 in CIN 2, and finally p53 in CIN 3/CIS.     

宫颈鳞癌中p16、p21WAF1、Rb、cyclinE蛋白的表达

目的通过观察p16、p21WAF1、Rb、cyclinE 4种细胞周期相关蛋白在宫颈鳞状细胞癌中的表达,探讨它们在宫颈癌的细胞周期调控中的作用.方法采用免疫组化Eli Vision二步法对88例宫颈鳞癌组织,16例宫颈上皮内病变(CIN)组织,15例宫颈炎组织进行p16、p21WAF1、Rb、cyclinE 4种蛋白表达的检测.结果p16、p21WAA1、cyclinE在宫颈癌中的表达高于宫颈炎(P＜0.05);Rb在宫颈癌的表达少于宫颈炎(P＜0.05);Rb与p16在宫颈癌中的表达呈负相关(r=-0.675,P＜0.05).结论宫颈癌细胞周期G1期中,由于Rb蛋白的缺失,使cyclinE表达升高,致使癌细胞增生;同时,p16、p21WAF1蛋白在宫颈癌中的表达增高,并失去抑制作用.