Adenocarcinoma ; pathology ; Adult ; Aged ; Carcinoma in Situ ; pathology ; Carcinoma, Squamous Cell ; pathology ; Cervical Intraepithelial Neoplasia ; pathology ; Cervix Uteri ; pathology ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Uterine Cervical Dysplasia ; pathology ; Uterine Cervical Neoplasms ; pathology ; Vaginal Smears ; classification ; Young Adult

Carcinoma of the uterine cervix is the most common malignant tumor in Korean women. It is well known that carcinogenesis is a multi-step event involoving the inactivation of tumor supressor genes, such as p53 gene and RB gene. The inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins. The pRB protein regulates early cell cyle progression by controlling transit through the G1 phase of the cell cyle. The p53 tumor suppressor gene product also plays a role in cell cycle control by the transcriptional regulation of cyclin-CDK inhibitor. Cervical carcinoma is an excellent model for studying the stepwise progression of cell transformation because this is reflected morphologically by the increasing dysplasia of the squamous cells before it becomes and invasive squamous cell carcinoma. The aim of this study was to examine the expression of pRB and compared that with overexpression of p53 in a series of cervical lesions including normal tissuess, dysplasias, carcinoma in situ and carcinomas by immunohistochemical staining with monoclonal antibody to elucidate the role of these tumor suppressor genes. The result were as follows: 1. In normal cervical mucosa and CIN I , a few positively stained cells for pRB were seen in basal and parabasal layer. 2. An abnormality of pRB, loss of expression was seen in 23.8% of CIN III and in 10.8% of invasive carcinoma. 3. Overexpression of p53 was demonstrated in 14.3% of CIN III and in 59.5% of invasive carcinoma. 4. The immunoreactivity of p53 was significantly increased (p<0.05) in stage II, III than stage I , whereas downregulation of pRB and tumor stage was not correlated. 5. The immunoreactivity of p53 was significantly increased (p<0.05) in squamous cell carcinoma than in adenocarcinoma, adenosquamous carcinoma and CIN III. These result suggest that an alteration of pRB is more frequently implicated in CIN III than invasive carcinoma, whereas overexpression of p53 may be involevd in late progression of uterine cervical carcinoma.
Adenocarcinoma ; Carcinogenesis ; Carcinoma in Situ ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell ; Cell Cycle Checkpoints ; Cervical Intraepithelial Neoplasia* ; Cervix Uteri ; Down-Regulation ; Female ; G1 Phase ; Genes, p53 ; Genes, Retinoblastoma ; Genes, Tumor Suppressor ; Humans ; Mucous Membrane ; Oncogene Proteins ; Retinoblastoma Protein*

OBJECTIVE: The purpose of this study was to evaluate the sensitivity, specificity and accuracy of a real-time optoelectronic device (TruScreen) as a diagnostic tool of cervical intraepithelial neoplasia (CIN) or cervical cancer. METHODS: Two hundred ninety two patients who had been presented with previously abnormal Papanicolaou (Pap) smear or abnormal colposcopic findings between February 2009 and September 2009 were analyzed. The sensitivities, specificities and accuracies of TruScreen and liquid-based cytology were evaluated. RESULTS: As a diagnostic tool of CIN, carcinoma in situ (CIS), and cervical cancer, TruScreen appeared sensitive enough compared with liquid-based cytology (82.8% vs 75.9%), but the difference is statistically not significant (P=0.687). Specificity and accuracy of TruScreen were similar to those of liquid-based cytology (specificity 81.4% vs 83.3%, accuracy 81.5% vs 82.5%). CONCLUSION: The present study suggests that the TruScreen could be an option as a tool of screening test in CIN, CIS, and cervical cancer and also be used combined with Pap smear.
Carcinoma in Situ ; Cervical Intraepithelial Neoplasia ; Humans ; Mass Screening ; Sensitivity and Specificity ; Uterine Cervical Neoplasms

OBJECTIVE: This study evaluated the effect of the specific human papillomavirus (HPV) genotypes on severity and prognosis in cervical intraepithelial neoplasia (CIN) patients. METHODS: The medical records of 446 patients treated with loop electrosurgical excision procedure (LEEP) were reviewed. The severity of CIN was categorized as CIN1/CIN2 versus CIN3+ including CIN3 and carcinoma in situ (CIS). HPV genotypes were categorized as 1) low risk, 2) intermediate risk, 3) high risk/HPV 16, 4) high risk/HPV 18, and 5) unclassified. Progression was defined as abnormal cytology, including atypical squamous cells, low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. The margin status and progression free survival (PFS) by HPV genotypes were analyzed in 355 women with three months or more of post-treatment records. RESULTS: CIN3+ was the most common CIN type (67.7%), and high risk/HPV 16 (26.9%) was the most common genotype. Intermediate risk (P < 0.01), high risk/HPV 16 (P < 0.01) and high risk/HPV 18 (P < 0.01) were significantly more common in women with CIN3+ than CIN1/CIN2. Patients with high risk/HPV 18 showed the highest rate of positive margins (P < 0.01). The margin status proved to be the only statistically significant factor affecting PFS. CONCLUSION: The proportion of positive margins was significantly different by HPV genotypes and highest in high risk/HPV 18 group. CIN patients with high risk/HPV 18 need to be more carefully tracked than patients with the other HPV genotypes.
Carcinoma in Situ ; Cervical Intraepithelial Neoplasia* ; Disease-Free Survival ; Female ; Genotype* ; Humans* ; Medical Records ; Prognosis* ; Track and Field

Carcinoma in Situ ; diagnosis ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; pathology ; Endometrial Hyperplasia ; pathology ; Female ; Humans ; Uterine Cervical Neoplasms ; pathology

OBJECTIVETo investigate the clinical significance of atypical squamous cells of unknown significance (ASCUS) with abnormal DNA ploidy in the early diagnosis of cervical lesions.

METHODSEight thousand four hundred and forty-eight patients were included in this study and all had DNA quantitative analysis and cervical liquid-based cytology. Among 1041 cases with DNA aneuploidy and/or abnormal cervical liquid-based cytology and additional cervical biopsy, histological review was performed in 247 ASCUS cases with abnormal DNA ploidy.

RESULTS(1) Among 8448 cases, 7877 were normal or benign, 426 were ASCUS, 45 were ASC-H, 55 were LSIL and 22 were HSIL by TBS diagnosis. The presence of 1-2 abnormal DNA ploidy cells was detected in 15.3% (65/426) of ASCUS, 11.1% (5/45) of ASC-H, 9.1% (5/55) of LSIL, and 0 (0/22) of HSIL. The presence of ≥ 3 abnormal DNA ploidy cells was detected in 39.0% (166/426) of ASCUS, 75.6% (34/45) of ASC-H, 76.4% (42/55) of LSIL, and 95.5% (21/22) of HSIL. (2) A total of 67 cases of CIN 2, CIN 3 or cancers were found in 247 patients with ASCUS by colposcopy biopsies, of which 13.9% (5/36) had 1-2 abnormal DNA ploidy cells, 45.5% (56/123) had ≥ 3 abnormal DNA ploidy cells and 6.8% (6/88) had normal DNA polidy. ASCUS with 1-2 abnormal DNA ploidy cells and with ≥ 3 abnormal DNA ploidy cells were compared. The difference was statistically significant (χ(2) = 11.79, P < 0.01). But the difference between ASCUS with 1-2 abnormal DNA ploidy cells and normal DNA ploidy had no statistical significance (P > 0.05).

CONCLUSIONSASCUS with ≥ 3 abnormal DNA ploidy cells has higher risk for developing CIN 2, CIN 3 or invasive carcinoma. The application of DNA quantitative analysis and cervical liquid-based cytology test can help in guiding clinical follow-up and treatment options in patients with ASCUS.

Adenocarcinoma ; diagnosis ; genetics ; pathology ; Adolescent ; Adult ; Aged ; Aneuploidy ; Carcinoma in Situ ; diagnosis ; genetics ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; genetics ; pathology ; Colposcopy ; DNA, Neoplasm ; genetics ; Female ; Humans ; Middle Aged ; Uterine Cervical Dysplasia ; diagnosis ; genetics ; pathology ; Uterine Cervical Neoplasms ; diagnosis ; genetics ; pathology ; Young Adult

OBJECTIVE: The Bethesda System (1991) recommended that the diagnosis of atypical squamous cells of undetermined significance (ASCUS) be qualified when possible to indicate whether a reactive process, or premalignant/malignant process, is favored. In order to evaluate the clinical significance of the qualification, we reviewed our hospital's experience with cervicovaginal smears diagnosed as ASCUS. METHOD: A retrospective study from June 1994 to December 2000 was performed on all cervicovaginal smears with the diagnosis of ASCUS. 3759 cases were included in study group. The 1200 cases of 3759 were not followed up. Histopathologic diagnosis and cervicovaginal smear results were reviewed and compared according to the qualification of ASCUS. The Chi-square test was used. RESULTS: Histopathologic diagnosis of low-grade squamous intraepithelial lesion (LGSIL) was seen in 46.1%, 47.8%, and 44.3% of the ASCUS FR, ASCUS FD and ASCUS NOS group, respectively. Histopathologic diagnosis of high-grade squamous intraepithelial lesion (HGSIL) was seen in 6.0%, 17.2% and 7.8% of the ASCUS FR, ASCUS FD and ASCUS NOS group, respectively. In ASCUS FR group, 1 invasive carcinoma was detected. In ASCUS FD group, 6 carcinoma in situ (CIS), 2 microinvasive carcinoma, 1 invasive carcinoma and 1 adenosquamous cell carcinoma were detected. In ASCUS NOS group, there were 20 CIS, 5 microinvasive carcinoma, 7 invasive carcinoma and 2 invasive adenocarcinoma. The ASCUS FD group demonstrated significant risk for SIL and more severe lesion but ASCUS FR and ASCUS NOS demonstrated no significant difference. CONCLUSION: ASCUS FD group has increased risk for detection of SIL or more severe lesion than ASCUS FR or ASCUS NOS group. But there were also significant number of SIL and even invasive cancer in ASCUS FR and ASCUS NOS group, so qualification of ASCUS was not useful for management and colposcopy-directed biopsy is advocated even in ASCUS FR group.
Adenocarcinoma ; Biopsy ; Carcinoma in Situ ; Diagnosis ; Retrospective Studies

Adenocarcinoma ; genetics ; pathology ; virology ; Carcinoma in Situ ; genetics ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; genetics ; pathology ; virology ; Cervix Uteri ; pathology ; virology ; Cytological Techniques ; DNA, Viral ; analysis ; Female ; Follow-Up Studies ; Humans ; Neoplasm Grading ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; Uterine Cervical Neoplasms ; genetics ; pathology ; virology

Epithelial cadherin (E-cadherin) is a Ca2+ -dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss is associated with an invasive and poorly differentiated phenotype in a wide range of tumors. Formalin-fixed, paraffin-embedded tissue sections from 36 cases of cervical intraepithelial neoplasia (CIN) and 14 cervical squamous cell carcinomas were investigated for the expression of E-cadherin immunohistochemically. While E-cadherin expression was usually restricted on the cell membrane of basal and parabasal cells in normal cervix, the presence of cytoplasmic E-cadherin was found to be associated with its grade in CIN lesions. Also, marked cytoplasmic staining was commonly revealed in poorly differentiated ones than well-differentiated squamous cell carcinomas. More intense reactivity of cytoplasmic E-cadherin was frequently seen in the foci of invasion than adjacent carcinoma in situ, and in its periphery than the center of tumor islands. In addition, DNA ploidy and S-phase fraction of squamous cell carcinomas were analyzed and compared with those of CIN lesion. We found that invasive squamous cell carcinomas more frequently disclosed DNA aneuploidy than CIN lesions, and there was correlation between cytoplasmic E-cadherin expression and DNA aneuploidy. Also, cytoplasmic E-cadherin-reactive cervical neoplasms had a higher rate of cell proliferation than that of membranous E-cadherin-reactive cases. These data suggest that the increased cytoplasmic E-cadherin expression may represent one of the abnormalities underlying the loss of polarity and invasiveness of cancer cells, and the abnormal E-cadherin expression combined with/without DNA ploidy or S-phase fraction may serve as a prognostic indicator.
Aneuploidy ; Cadherins* ; Carcinoma in Situ ; Carcinoma, Squamous Cell* ; Cell Membrane ; Cell Polarity ; Cell Proliferation ; Cervical Intraepithelial Neoplasia ; Cervix Uteri* ; Cytoplasm ; DNA* ; Female ; Islands ; Phenotype ; Ploidies* ; Uterine Cervical Neoplasms

OBJECTIVETo investigate the differential expressions of nucleolin in invasive cervical squamous cell carcinoma, cervical intraepithelial neoplasms (CIN) and normal cervical epithelial tissues and explore the role of nucleolin in the carcinogenesis and progression of cervical squamous cell carcinoma.

METHODSFifty specimens of invasive cervical squamous cell carcinoma, 65 specimens of CIN, and 60 adjacent normal cervical epithelial tissue specimens were examined immunohistochemically for nucleolin expression. The correlation of nucleolin expression levels with histological grades of invasive cervical squamous cell carcinoma and CIN were analyzed.

RESULTSThe specimens of invasive cervical squamous cell carcinoma showed a significantly higher positivity rate for nucleolin expression than CIN and normal cervical epithelial tissues, and the rate in CIN tissues was significantly higher than that in normal cervical epithelial tissues (P<0.01). The expression level of nucleolin was significantly higher in invasive cervical squamous cell carcinoma than in CIN and normal cervical epithelia tissues, and higher in CIN than in normal cervical epithelia tissues, whose immunostaining scores were 7.6±0.3, 6.1±0.2, and 3.0±0.2, respectively (P<0.01). The mean nucleolin immunostaining score was significantly higher in poorly and moderately differentiated than in highly differentiated cervical squamous cell carcinoma (7.9 vs 7.1, P<0.01), and higher in high grade CIN than in low grade CIN tissues (6.0 vs 4.0, P<0.01).

CONCLUSIONSOverexpression of nucleolin plays an important role during carcinogenesis of cervical squamous cell carcinoma and is positively correlated with tumor progression of CIN and cervical squamous cell carcinoma.

Carcinogenesis ; Carcinoma in Situ ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; Disease Progression ; Female ; Humans ; Phosphoproteins ; metabolism ; RNA-Binding Proteins ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology