Telomerase Activation inin Vitroandin VivoCervical Carcinogenesis

Telomerase activity is found in the majority of human cancers, but not in most normal tissues. It is generally accepted that there is a multistep process in human carcinogenesis. Studying the role of telomerase activation in this process may provide new information to further our understanding of the pathological process of clinical lesions. In the present study, telomerase activity was found in HPV-immortalized and cigarette smoke condensate (CSC)-transformed malignant cell lines established in a cervical carcinogenesis model and in cell lines derived from cervical intraepithelial neoplasias (CINs) and carcinomas. With exfoliated cell samples, telomerase activity was detected in 3 of 41 (7%) normal cervices, 10 of 25 (40%) CINs, and all 20 (100%) carcinomas. Telomerase activation was significantly higher in CINs than in normal cervices (χ²= 7.42,P< 0.01) and was much higher in invasive carcinomas than in CINs (χ²= 18.00,P< 0.005). Our observations suggest that telomerase activation is a relatively early-stage event in cervical carcinogenesis, and this activation is associated with the initiation and progression of cervical lesions. Detection of telomerase activity may serve as a tool for diagnosis and prognosis of cervical neoplasias.     

子宫颈癌及其癌前病变组织端粒酶活性的研究

目的研究宫颈癌及其癌前病变组织中端粒酶激活的意义.方法应用端粒酶重复序列扩增-酶联免疫吸附法(TRAP-ELISA)及电泳-银染法,对36例宫颈浸润癌及16例宫颈上皮内瘤变(CIN)组织进行端粒酶活性测定,以吸光度(A)值判断端粒酶活性.同时测定11例正常宫颈、6例慢性宫颈炎症及8例癌旁组织端粒酶活性作为对照.结果CIN、宫颈癌及对照组端粒酶活性A值分别为0.398±0.293、1.580±0.819和0.050±0.012,3组比较,差异有极显著性(P＜0.01).端粒酶活性高低与肿瘤分化程度呈负相关,与淋巴结转移呈正相关;与组织学类型、分期、体积大小无关.结论端粒酶的激活发生在宫颈癌病变的早期,可能成为宫颈癌及癌前病变早期诊断和鉴别诊断的指标.     

子宫颈上皮内瘤变端粒酶活性的研究

目的探讨端粒酶激活在宫颈癌变过程中的意义及其作为病情监测方法和预测宫颈上皮内瘤变(CIN)结局的可能性.方法采用端粒重复序列扩增-聚合酶链反应(PCR-TRAP)方法检测了64例CIN患者、21例宫颈癌患者、20例慢性宫颈炎患者及15例正常宫颈妇女宫颈脱落细胞、宫颈活组织检查(活检)组织的端粒酶活性.结果正常宫颈、慢性宫颈炎、CINⅠ级(CINⅠ)、CINⅡ级(CINⅡ)、CINⅢ级(CINⅢ)及宫颈癌患者的宫颈脱落细胞端粒酶的阳性表达率分别为20.0%、25.0%、62.5%、60.0%、82.4%及61.9%;对应的活检组织端粒酶的阳性表达率分别为26.7%、30.0%、50.0%、45.0%、96.4%及95.2%;随着宫颈病变的进展,端粒酶阳性表达率呈逐渐增高趋势(X2细胞=16.28、X2组织=36.98,P均＜0.05).CINⅠ、CINⅡ端粒酶阳性表达率比较,差异无显著性(P细胞=0.24、P组织=0.25);CINⅢ端粒酶阳性表达率高于CINⅠ、CINⅡ(P细胞=0.03、P组织=0.000012);CINⅢ与宫颈癌活检组织端粒酶阳性表达率比较,差异无显著性(P=0.05);宫颈脱落细胞与宫颈活检组织的端粒酶检测结果的对应性良好(X2=46.4,P＜0.05).结论端粒酶激活与宫颈癌变的进程有关,宫颈脱落细胞端粒酶活性检测可以作为CIN病情检测、处理及预后估计的辅助指标.     

Are Women with Antecedent Low-Grade Cytology and

《Journal d'obstetrique et gynecologie du Canada》2022,44(10):1054-1060

Telomerase activity in Papanicolaou smear-negative exfoliated cervical cells and its association with lesions and oncogenic human papillomaviruses

OBJECTIVE: The goal of this study was to evaluate telomerase activity in exfoliated cervical cells and its association with cytology, pathology, and human papillomavirus (HPV). METHODS: Telomerase activity and HPV DNA sequences were examined in the exfoliated cervical cells from a general population of 245 women aged more than 30 years undergoing routine cervical screening by Papanicolaou smear. The women who were found to have telomerase activity or abnormal cytology in their exfoliated cervical cells were examined for cervical lesions by colposcopy and biopsy. RESULTS: Cytology for our population (mean, 56 years) revealed only one abnormal smear (1/245, 0.4%), in which a cervical intraepithelial neoplasia grade I (CIN I) lesion was found. The exfoliated cervical cells used to prepare the smear were negative for telomerase and contained low-risk HPV DNA. Telomerase activity was found in 16 exfoliated cell samples (16/245, 6.5%); high-risk HPV DNA was found in 9 of these samples (9/16, 56%) and 9 of the biopsy specimens that could be evaluated from patients testing positive for telomerase revealed CIN I lesions (9/11, 82%). CONCLUSIONS: Telomerase activity is often associated with high-risk HPV infection and it is suggested that telomerase assay can help to detect occult cervical lesions.     

Prevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus

Objectives.The objective was to evaluate the sensitivity and specificity of cervical cytology in women infected with the human immunodeficiency virus (HIV), risk factors for abnormal cytology in HIV-infected and uninfected women, and risk factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-infected women.Methods.Methods included a cross-sectional analysis of cervical cytology, colposcopic impression, and histology in 248 HIV-infected women and multivariate analyses of risk factors for abnormal cytology in 253 HIV-infected and 220 uninfected women and risk factors for CIN in 186 HIV-infected women.Results.The sensitivity and specificity of cytology for all CIN grades were 0.60 and 0.80 and, for high-grade CIN, 0.83 and 0.74. The prevalence of abnormal cytology was 32.9% in HIV-infected and 7.6% in HIV-negative women. Independent risk factors for abnormal cytology were immunodeficiency [odds ratio (OR) 8–17,P< 0.001] and human papillomavirus (HPV) infection (OR = 5,P< 0.001). The prevalence of CIN on histology was 32% in HIV-infected women, and the only independent risk factor for CIN was oncogenic HPV type (OR = 5,P= 0.005).Conclusion.Given the high prevalence of abnormal cytology and CIN in HIV-infected women, cytologic screening has significant limitations. Both immunodeficiency and type of HPV infection are important risk factors.     

Stathmin在宫颈癌中的表达及意义

目的:探讨Stathmin/oncoprotein18(Op18)蛋白在宫颈癌的表达及意义。方法:应用免疫组化和Westernblot法检测15例正常宫颈组织、26例宫颈上皮内瘤变组织和52例宫颈癌组织中Stathmin蛋白的表达。结果:用免疫组化检测Stathmin蛋白在正常宫颈组织、宫颈上皮内瘤变及宫颈癌的阳性表达率分别为20.00%、53.85%、84.62%。正常宫颈组织组分别与宫颈上皮内瘤变及宫颈癌组比较,差异均有统计学意义(P<0.05);宫颈上皮内瘤变组与宫颈癌组比较,差异有统计学意义(P<0.05)。Westernblot法检测显示,正常宫颈组分别与宫颈上皮内瘤变组、宫颈鳞癌组及宫颈腺癌组比较,差异均有统计学意义(P<0.01),宫颈上皮内瘤变组分别与宫颈鳞癌组及宫颈腺癌组比较,差异均有统计学意义(P<0.01)。Stathmin与宫颈癌的临床分期、组织分级、区域淋巴结转移有关。结论:Stathmin在宫颈癌过表达,与宫颈癌的发生、发展密切相关。     

Human papillomavirus genotyping using HPV DNA chip analysis in Korean women

This study was designed to investigate the genotypes of human papillomavirus (HPV) in Korean women who had abnormal cervical cytology and to evaluate the clinical accuracy of HPV DNA chip analysis for the diagnosis of cervical neoplasia. Liquid-based cytology preparations, HPV DNA chip analysis, and cervical biopsy were performed in 2358 women. High-risk HPV was identified in 23.5% of 1650 histologically confirmed normal samples (including cervicitis and squamous metaplasia) and in 81.8% of 708 samples with cervical intraepithelial neoplasia (CIN) and carcinoma (P<0.01). The major prevalent high-risk HPV genotypes in 381 samples of CIN II/III were HPV-16, -58, -33, and -31, in order of prevalence rate (average overall, 78.0%), and HPV-16, -18, -58, and -33 (average overall, 81.2%) in 133 samples of squamous cell carcinoma (SCC). The infection rate of HPV-16 was significantly higher than that of other high-risk HPV genotypes in all normal, CIN, and SCC cases (P < 0.01) and increased with more advanced squamous cervical lesions (P<0.01). The detection accuracy of high-risk HPV using HPV DNA chip analysis for CIN II or worse was as follows: sensitivity 84% (81-87%), specificity 72% (70-74%), positive predictive value 47% (44-50%), and negative predictive value 94% (92-95%). These results suggest that HPV DNA chip analysis may be a reliable diagnostic tool for the detection of cervical neoplasia and that there are geographic differences in the distribution of high-risk HPV genotypes.     

The value of p16ink4a expression by fluorescence in situ hybridization in triage for high risk HPV positive in cervical cancer screening

Objectives

The aim of this study is to evaluate the effect of fluorescence in situ hybridization (FISH) detection for p16ink4a expression as an alternative triage for high risk HPV positive women in cervical cancer screening.

Methods

Totally 191 cervical cell specimens from women with HPV positive were collected. The p16ink4a expression by FISH and liquid-based thin-layer cytology was performed and followed by colposcopy with or without biopsied histologic examination for all participants. The relationship between p16ink4a expression and histologic diagnosis, as well as cytology was analyzed.

Results

The positive rate of p16ink4a was 5.35% in normal or inflammation cases, 56.67% in CIN 1, 83.78% in CIN 2-3, 100.00% in carcinoma, respectively, with a significance between < CIN2 and ≥ CIN 2 (P < 0.001). The p16ink4a expression presented a concordance trend as cytology grading, with a positive rate of 9.28% in NILM, 33.33% in ASCUS, 53.37% in LSIL, 81.25% in ASC-H, and 95% in HSIL, respectively. Compared with cytology, FISH detection for p16ink4a had a higher accuracy (84.8% vs. 74.34%), higher sensitivity (87.75% vs. 52.00%) and similar specificity (83.84% vs. 88.79%) for predicting ≥ CIN 2 lesions.

Conclusions

FISH detection specific to p16ink4a presents a high consistency with cytologic grading and has a higher accuracy for predicting high grade CIN than cytology in high risk HPV positive women. Our findings suggest that FISH detection for p16ink4a is a potential alternative triage for high-risk HPV positive women in cervical cancer screening.     

Dynamin 2 expression as a biomarker in grading of cervical intraepithelial neoplasia

Objective

Dynamin 2, which plays a role in endocytosis, is known to be required for HPV infection on host cells. We investigated dynamin 2 as a biomarker in grading of cervical intraepithelial neoplasia (CIN) by comparing with Ki-67 expression and the type of HPV infection (low-risk vs. high-risk).

Study design

We performed immunohistochemical stains of dynamin 2 and Ki-67 on tumor samples of patients with CIN and the type of HPV infection was investigated.

Results

All the patients with reactive changes (n = 7) or normal (n = 4) did not show dynamin 2 expression. There were 33, 14, and 12 cases with CIN I, II, and III, respectively, and there was a negative correlation between the degree of dynamin 2 expression and the severity of CIN lesions with statistical significance (P < 0.001). Negative expression of dynamin 2 was more sensitive for the detection of CIN II/III than high expression (2+) of Ki-67 (96.2% vs. 73.1%, P = 0.041). Among patients in whom HPV infection was detected, the degrees of dynamin 2 expression were not associated with the type of HPV infection (low-risk vs. high-risk). Overall, there was a negative correlation between the expression patterns of Ki-67 and dynamin 2.

Conclusion

We found that dynamin 2 may be a helpful biomarker in grading of CIN lesions and a candidate biomarker for detecting low grade CIN with high sensitivity.     

Increased frequency of abnormal Papanicolaou smears in adolescents

Abnormal Papanicolaou smears has increased in adolescents. Our objective was to analyze the frequency of cervical intraepithelial neoplasia (CIN) in adolescents (<20 years of age) over the last 12 years, comparing to adult (≥20 years of age). We studied 110,283 (10.85% of adolescents) reports from Papanicolaou smears between 1987 and 1999 in a public university hospital that has a screening program for cervical cancer prevention. The tests were divided into 3 periods (1987–1991, 1992–1995 and 1996–1999) for studying the evolution of frequencies. CIN I was more frequent among adolescents (1.73% vs. 0.99%) and CIN III and invasive cancer among adult women (0.62% vs. 0.05%, and 0.39% vs. 0.0083%, respectively). Between the periods 1987–1991 and 1996–1999 there was an increased in the frequency of CIN I among adolescents (from 0.78–2.17%) and adults (from 0.72–1.16%); CIN II decreased among adult patients (from 0.52–0.28%) and tripled among adolescents over recent years (from 0.15–0.47%), and CIN III increased in both group, although without statistical significance. One case of invasive carcinoma among adolescents occurred in the period from 1996–1999. We strongly recommend the inclusion of adolescent populations in the screening programs, from the time that they begin sexual activity. Received: 10 April 2001 / Accepted: 11 June 2001     

Detection of cervical neoplasia by DNA methylation analysis in cervico-vaginal lavages, a feasibility study

Objective

To explore the feasibility of DNA methylation analysis for the detection of cervical neoplasia in self-obtained cervico-vaginal lavages.

Methods

Lavages collected by a self-sampling device and paired cervical scrapings were obtained from 20 cervical cancer patients and 23 patients referred with an abnormal cervical smear (15 with high-grade cervical intraepithelial neoplasia (CIN2+) and 8 without CIN). All lavages and scrapings were analyzed by liquid based cytology (LBC), Hybrid Capture II (HC-II) for hr-HPV DNA detection and by DNA methylation analysis (JAM3, TERT, EPB41L3 and C13ORF18). Concordance between lavages and scrapings was measured by Cohen's Kappa (k).

Results

In lavages and scrapings from cervical cancer patients (n = 20), methylation analysis was positive in 19 (95%) and 19 (95%), HC-II in 16 (80%) and 15 (75%) and LBC in 15 (75%) and 19 (95%), respectively. In lavages and scrapings from CIN2+ patients (n = 15), methylation analysis was positive in 10 (67%) and 12 (80%), HC-II in 15 (100%) and 15 (100%) and LBC in 11 (73%) and 12 (80%), respectively. Concordance between cervical scrapings and lavages (n = 43) was for LBC k = 0.522 (p < 0.001), hr-HPV testing k = 0.551 (p < 0.001) and DNA methylation analysis k = 0.653 (p < 0.001).

Conclusions

DNA methylation analysis in cervico-vaginal lavages obtained by a self-sampling device is feasible and its diagnostic performance appears to be at least comparable to the detection of cervical neoplasia by cytomorphology and hr-HPV. Our pilot study suggests that detection of cervical neoplasia by DNA methylation analysis in cervico-vaginal lavages warrants exploration of its use in large prospective studies.     

Oral contraceptives and human papillomavirus infection in cervical intraepithelial neoplasia

Summary We report about 142 patients from whom colposcopically directed cervical punch biopsies were taken which showed condylomatous lesions with or without cervical intraepithelial neoplasia (CIN). Fiftysix (39.4%) of these women used oral contraceptives (OC) for at least two years before examination. We used DNA in situ hybridization on all biopsies for detection of human papillomavirus (HPV)-DNA. Among OC users a significant trend towards higher HPV infection rates in high grade CIN (odds ratio 2.9,P<0.05) was found, whereas non-users of oral contraceptives had the highest HPV infection rate in condylomatous lesions without CIN (odds ratio 0.5,P<0.05). Thus in OC users HPV infection was about 24 times more likely in CIN III as in condyloma, whilest among non-users the trend was the other way round (7-fold likelyhood of HPV positivity in condyloma compared to CIN III). Other known risk factors for cervical carcinoma did not influence HPV infection rates in either group.     

Poor correlation of high-grade cervical dysplasia with referral cytology: clinical implications

Objective: We questioned the diagnostic utility of cervical cytology by studying whether women with colposcopically guided biopsy proven high-grade cervical dysplasia or cancer had referral cytology results that correlated highly with their disease.Methods: All women with any cytologic abnormality or visible lower tract lesion(s) are referred for colposcopic examination. Ten thousand visits to our colposcopy clinic were prospectively collected, tracked, and reviewed, which revealed 566 cases of high-grade dysplasia and 8 cancers on biopsy. The proportion of high grade disease that was discovered by high grade cytology was measured.Results: The diagnosis of high grade cervical disease was not preceded by high-grade cytology (HGSIL) or “rule out cancer” cytology result (n = 95, 16.8%) in the majority of cases (P < .0001, χ²). High-grade disease was more often preceded by low-grade cytology (LGSIL) (n = 224, 39.5%), followed by atypical Papanicolaou smears (ASCUS) (n = 220, 38.9%) and visible cervical or vaginal lesion(s) (n = 27, 4.8%). A very high percentage of cancer cases had preceding HGSIL cytology (6 of 8 cases at least HGSIL, 75%).Conclusion: High-grade cervical neoplasia was more likely to be discovered following colposcopic triage of “minor” Papanicolaou smear abnormalities (ASCUS or LGSIL). The false negative rate of a single Papanicolaou smear to detect dysplasia may be as high as 65% (with specificity at the 90% range) (Fahey MT, Irwig L, Macaskill P. Meta analysis of Pap test accuracy. Am J Epidemiol 1995;141:7:680–9), making cytology an inaccurate diagnostic replacement for colposcopy. We should rethink the significance of minimally abnormal Papanicolaou smears when designing triage protocols that delay or eliminate colposcopy based on the Bethesda Grading System alone.     

Evaluation of adenoassociated virus 2 and human papilloma virus 16 and 18 infection in cervical cancer biopsies

OBJECTIVE: Protective roles of adenoassociated virus (AAV) 2 in cervical tumorigenesis are controversial. In an effort to clarify this issue, we tested prevalence of AAV 2 and human papillomavirus (HPV) infection in cervical lesions and adjacent normal tissues. METHODS: Tissues of cervical intraepithelial neoplasm (CIN) I (20 patients), CIN II (24 patients), CIN III (25 patients), and invasive cancer (23 patients) were investigated by microdissection and PCR using HPV-16-, HVP-18-, and AAV-2-specific primers. RESULTS: AAV 2 was detected in 11 out of 20 CIN I (55%), 21 out of 24 CIN II (84.5%), 13 out of 25 CIN III (52%), and 12 out of 23 invasive cancer cases (52.2%). However, HPV 16 was detected in none out of 20 CIN I, 2 out of 24 CIN II (8.3%), 6 out of 25 CIN III (24%), and 6 out of 23 invasive cancer cases (26.1%). HPV 18 was detected in 1 case in CIN II (4.2%) and 2 cases in CIN III (8%). In 92 perilesional normal tissues, AAV 2 was detected in 53 cases (57.6%), displaying 25% of CIN I, 83.3% of CIN II, 52% of CIN III, and 65.2% of invasive cancer. CONCLUSION:The differences in AAV 2 prevalence are not significant between CIN and normal tissues. However, differences in HPV 16 are significant in CIN III and invasive cancer, as compared to CIN I, CIN II, and normal, suggesting no significant correlation between AAV 2 and cervical cancer. Thus, these results support the notion that AAV 2 is not associated with cervical tumorigenesis.     

Cervical intraepithelial neoplasia III: long-term follow-up after cold-knife conization with involved margins

OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia (CIN) III or squamous carcinoma in situ after cold-knife conization with involved margins. METHODS: A total of 390 patients (median age 39 years, range 20-69) with positive margins after cold-knife conization for CIN III were followed expectantly for a mean of 19 (range 6-30) years. Follow-up consisted of colposcopy, cytology, histology, and pelvic examination. RESULTS: Overall, 306 (78%) patients remained free of CIN III, and 84 (22%) had persisting or recurrent CIN III (n = 78) or developed invasive carcinoma (n = 6). Fifty-three patients had persisting CIN III (diagnosed within 1 year of conization), 25 developed recurrent CIN III after a median of 3 (range 2-28) years, five developed microinvasive carcinomas (at 3, 6, 7, 12, and 23 years), and one developed a stage IB carcinoma at 8 years. Persisting or recurrent disease was more common in patients in whom both the endocervical and the ectocervical cone margins were involved than in those in whom only the ectocervical or the endocervical margin was positive (52% versus 17% and 21%, respectively, P <.001). CONCLUSION: Expectant management is reasonable for patients with CIN III and positive margins after cold-knife conization. However, these patients require careful follow-up, particularly during the first year.     

肿瘤干细胞相关基因ABCB1、ABCG2表达与宫颈上皮恶变及发展关系的研究

目的:探讨肿瘤干细胞相关基因ABCB1、ABCG2表达与宫颈癌形成及临床病理参数之间的关系。方法:应用组织芯片技术和免疫组织化学检测宫颈浸润癌34例、微小浸润癌30例、CINⅢ30例、宫颈慢性炎症30例患者ABCB1、ABCG2的表达,并与临床病理资料进行相关性分析。结果:ABCB1在浸润癌、微小浸润癌、CINⅢ、宫颈慢性炎症中的阳性表达率分别是为76%(26/34)、60%(18/30)、40%(12/30)、20%(6/30),其阳性表达率随病变级别升高而明显增加;ABCB1在浸润癌中表达水平与肿瘤分化程度、TNM分期、淋巴结转移密切相关(P<0.05),与肿瘤体积无关(P>0.05);ABCG2在浸润癌、微小浸润癌、CINⅢ、宫颈慢性炎症中的阳性表达率分别为80%(27/34)、70%(21/30)、40%(12/30)、30%(9/30),其阳性表达率随病变级别增加而上升;ABCG2表达水平与肿瘤体积、TNM分期密切相关(P<0.05),与淋巴结转移、肿瘤分化程度无关(P>0.05)。结论:ABCB1、ABCG2在促进宫颈癌变过程中发挥主要作用,并且ABCB1的阳性表达是提示宫颈癌预后不良的客观指标。     

Atypical squamous cells of undetermined significance in postmenopausal women: a comparative retrospective analysis

Objectives

To determine the outcomes of women with a diagnosis of atypical squamous cells of undetermined significance (ASCUS) with respect to menopausal status.

Study design

Between October 2006 and March 2010, the data of 214 postmenopausal women with ASCUS results on Pap smear were evaluated. Sociodemographic data and histopathological results were compared with those of 1018 premenopausal women with ASCUS cytology.

Results

At the final diagnosis, most histological findings were normal in pre- and postmenopausal women with ASCUS cytology (70% and 70.1%, respectively). In the premenopausal group, 23.1% of the women had cervical intra-epithelial neoplasia (CIN) 1 lesions and 6.7% had CIN 2/3 lesions. Similarly, CIN 1 and CIN 2/3 lesions were detected in 23.4% and 6.1% of postmenopausal women, respectively. No significant difference in the final diagnosis was found between the two groups (p = 0.88). Two premenopausal women (0.2%) and one postmenopausal woman (0.5%) had micro-invasive cervical carcinoma. There were no cases of invasive carcinoma in either group.

Conclusions

According to this study, the rates of pre-invasive and micro-invasive cervical carcinoma were similar in pre- and postmenopausal women with ASCUS cytology.     

Disruption of precise regulation of αPKC expression and cellular localization is associated with cervical cancer progression

Purpose

To understand the pathogenesis of cervical cancer (CC) associated with polarity protein αPKC and the potential roles of αPKC in clinical management of CC.

Methods

Tissue samples were collected from women who received colposcopy biopsy or hysterectomy surgery, including 9 CIN1, 8 CIN2, 15 CIN3, and 12 invasive cervical squamous cancer (ICC). 16 normal controls were from the normal region of tumor samples, HE and immunofluorescence staining of αPKC were performed on these samples. ANOVA and Kruslal-wallis test were used to quantitate the abnormal distribution and expression level of αPKC among different cervical lesions.

Results

Disruption of polarized apical localization and increased cytoplasmic accumulation of αPKC were identified in cervical lesions. In normal cervical epithelium, αPKC was detected on the apical membrane of endocervical columnar epithelial cells and of exocervical epithelial cells located at basal layer of squamous epithelium. While in squamous metaplasia, a precancerous lesion of cervical neoplasia, the polarized apical membrane localization of αPKC was disrupted, and intensed cytoplasmic accumulation was identified in the immature squamous metaplastic cells. Compared with normal cervix, number of epithelial cells with abnormal αPKC distribution was progressively increased in CINs and ICC (P < 0.05), and cytoplasmic accumulation of αPKC was increased in CIN2, CIN3, and ICC compared with CIN1 (P < 0.05).

Conclusions

Disruption of polarized apical localization and increased cytoplasmic accumulation of αPKC were associated with CC progression, indicating that precise regulation of αPKC may play important roles in CC progression, and αPKC may be a potential molecular target for clinical diagnoses and treatment of CC.     

The role of p53, Bcl-2 and Ki-67 in premalignant cervical lesions and cervical cancer

PURPOSE: The aim of this study was to determine the role of p53, Bcl-2 and Ki-67 expression in the carcinogenesis of cervical carcinoma and aggressiveness of cervical intraepithelial neoplasia (CIN). METHODS: The pathology specimens of 63 patients with a diagnosis of normal squamous epithelium (22 cases), CIN I (14), CIN II (5), CIN III (8) and squamous cell carcinoma (14) were evaluated immunohistochemically for the expression of p53, Bcl-2 and Ki-67 in paraffin sections. RESULTS: The expression of p53 and Ki-67 increased proportionally to the grade of CIN and cervical cancer, but only the increase of p53 expression was statistically significant (p = 0.002). There was no significant correlation between Bcl-2 expression and premalignant and malignant cervical lesions. CONCLUSION: p53 expression may have a role in the carcinogenesis of squamous cell cervical carcinoma whereas Bcl-2 expression has no role. Ki-67 expression can not be used in determining the aggressiveness of CIN lesions.