Immunohistochemical Localization of Cdc6 in Squamous and Glandular Neoplasia of the Uterine Cervix

2002 ◽  
Vol 126 (10) ◽  
pp. 1164-1168
Author(s):  
Lian Bonds ◽  
Paige Baker ◽  
Carol Gup ◽  
Kenneth R. Shroyer

Abstract Context.—Cdc6 has been extensively studied as a marker for cellular proliferation that is expressed during the normal cell cycle. Recent studies indicate that Cdc6 may be a marker for cervical intraepithelial neoplasia (CIN) and carcinoma; however, the histologic distribution of Cdc6 has not been explicitly defined. Expression of Cdc6 in the endocervical mucosa also remains unexplored. Objective.—The goal of the current study was to evaluate the distribution of Cdc6 protein, MIB-1 protein, and human papillomavirus (HPV) DNA in a broad range of cervical tissues, including normal, potentially premalignant, and malignant lesions of the ectocervical and endocervical mucosa. Methods.—We used an indirect immunoperoxidase method to stain formalin-fixed, paraffin-embedded tissues and frozen tissues, including biopsy and hysterectomy specimens, for Cdc6 and MIB-1 proteins, and we used in situ hybridization to detect HPV DNA in a subset of cases. Results.—Cdc6 staining was exclusively nuclear and was present in both squamous and glandular epithelial cells of histologic sections. Cdc6 staining was rarely present in specimens of normal cervical squamous mucosa (2/84, 2.4%) or in specimens with squamous metaplasia (3/59, 5.1%) and was not detected in normal endocervical glands (0/84). Staining was present in most cases of CIN I (31/48, 65%). Staining was present in the majority of cases of CIN II (25/28, 89%) and in all cases of CIN III (36/36) and squamous cell carcinomas (34/34). The proportion of cells staining for Cdc6 increased with the grade of dysplasia, and the proportion of stained cells in squamous cell carcinomas was similar to that in lesions of high-grade dysplasia. Cdc6 staining was present in the majority of cases in glandular lesions including adenocarcinoma in situ (11/14, 79%) and adenocarcinoma (8/10, 80%). The histologic distribution of Cdc6-immunoreactive cells was similar to that of cells with a strong signal for HPV DNA, but Cdc6 protein and HPV DNA did not colocalize at the level of individual cells. Conclusion.—Cdc6 expression is a marker for high-grade cervical squamous and glandular dysplasia and carcinoma and is associated with HPV infection. The mechanistic basis of the association between HPV infection and Cdc6 immunopositivity remains to be determined but may represent either up-regulation of Cdc6 expression or stabilization of the Cdc6 protein.

Author(s):  
Margaret M. Madeleine ◽  
Lisa G. Johnson

Vulvar and vaginal cancers are rare and predominantly involve squamous cell carcinomas. Some studies combine these cancers, presumably because of their rarity, anatomic proximity, and shared risk factors. Major risk factors include human papillomavirus (HPV) and cigarette smoking. This chapter explores the similarities and important differences in etiology between these cancer sites. In addition to its focus on invasive cancer, the chapter also discusses high-grade precursor lesions, or in situ disease, that sometimes progress to cancer and must, therefore, be treated.


2004 ◽  
Vol 128 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Andrew A. Renshaw ◽  
Dina R. Mody ◽  
Richard L. Lozano ◽  
Emily E. Volk ◽  
Molly K. Walsh ◽  
...  

Abstract Context.—Adenocarcinoma in situ of the cervix is a recently recognized interpretation in the Bethesda 2001 system. Although specific morphologic criteria have been published, recognizing this entity is still difficult. Objective.—To compare pathologists' ability to correctly identify and categorize adenocarcinoma in situ with their ability to identify and categorize adenocarcinoma, high-grade squamous intraepithelial lesion, and squamous cell carcinoma. Design.—Pathologists' reviews in the 2001 and 2002 College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology Program, an interlaboratory comparison program for gynecologic cytology, were examined. Cases were usually reviewed by multiple pathologists. False-negative rates, the percentage of reviews with exact agreement with reference interpretations, and the percentage of cases in which all reviews were in exact agreement with the reference interpretation for adenocarcinoma in situ, adenocarcinoma, high-grade squamous intraepithelial lesion, and squamous cell carcinoma were compared. Results.—A total of 213 reviews of cases categorized as adenocarcinoma in situ were compared with 2821 reviews of adenocarcinoma, 7535 reviews of high-grade squamous intraepithelial lesion, and 1886 reviews of squamous cell carcinoma. The false-negative rate for adenocarcinoma in situ (11.7%) was significantly higher than that for high-grade squamous intraepithelial lesion (4.6%, P < .001) and squamous cell carcinoma (3.3%, P < .001) but not for adenocarcinoma (8.9%, P = .16). Of all the reviews of adenocarcinoma in situ cases, 46.5% were interpreted specifically as adenocarcinoma in situ, compared to 72.2% of reviews of adenocarcinoma, 73.2% of high-grade squamous intraepithelial lesion, and 75.1% of squamous cell carcinoma. No individual case of adenocarcinoma in situ was always specifically recognized as adenocarcinoma in situ; 26.5% of cases of adenocarcinoma were specifically recognized as such in all reviews. Findings were similar with and without the inclusion of high-grade squamous intraepithelial lesion/carcinoma, not otherwise specified, as an acceptable review interpretation for cases of adenocarcinoma, squamous cell carcinoma, and high-grade squamous intraepithelial lesion. Conclusion.—These data from expert-referenced and biopsy-proven cases suggest that adenocarcinoma in situ is not as easily recognized or categorized as other serious diagnoses.


2015 ◽  
Vol 7 (3) ◽  
pp. 329-334 ◽  
Author(s):  
Georgios Nikolakis ◽  
Ioannis Karagiannidis ◽  
Vasiliki A. Zampeli ◽  
Andreas Altenburg ◽  
Martina Brunner ◽  
...  

Human papilloma virus (HPV) infection is documented to be involved in the development of epithelial malignancies, mostly in cervical cancer. Systemic lupus erythematosus (SLE) patients have an increased prevalence of such an infection. We report the case of a 55-year-old female SLE patient who developed multiple in situ squamous cell carcinomas on her fingers, after chronic HPV infection. HPV-33 DNA was isolated from the lesions. The purpose of this case presentation is to raise awareness about HPV-induced malignancies for this high-risk group and propose an early HPV vaccination to efficiently prevent such comorbidities.


2006 ◽  
Vol 20 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Elena Riet Correa Rivero ◽  
Fabio Daumas Nunes

Human Papilomaviruses (HPV) are a group of viruses associated with benign and malignant lesions of cutaneous and mucosal epithelia. Some "high risk" HPV types, especially HPV 16 and 18, are strongly correlated with cervical and anogenital cancers and are also related to the genesis of oral squamous cell carcinomas (OSCC). The aim of this work was to investigate the incidence of HPV infection in 40 paraffin-embedded or fresh specimens of OSCC, using PCR amplification of the viral DNA. Literature based primers (GP5+/GP6+) were used in order to amplify HPV DNA from the L1 gene, present in more than 22 types of HPV. A condyloma case with HPV 16 and 18 detected by in situ hybridization was used as a positive control. Amplification of HPV was observed only in the positive control. No squamous cell carcinoma cases showed DNA viral amplification. Absence of HPV DNA amplification by PCR in the analyzed specimens of OSCCs suggests that this virus not always plays a role in the carcinogenesis process. Discrepancy with some studies found in the literature may be related to methodology or population differences.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Severien Van Keer ◽  
Annina P. van Splunter ◽  
Jade Pattyn ◽  
Annemie De Smet ◽  
Sereina A. Herzog ◽  
...  

AbstractHost cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59–0.92) and 0.76 (95% CI 0.58–0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.


Virology ◽  
2007 ◽  
Vol 369 (1) ◽  
pp. 182-190 ◽  
Author(s):  
T. Matsha ◽  
H. Donninger ◽  
R.T. Erasmus ◽  
D. Hendricks ◽  
A. Stepien ◽  
...  

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