Immunohistochemical evaluation of ProEx C in human papillomavirus-induced lesions of the cervix

Conesa‐Zamora, Pablo; Doménech-Peris, Asunción; Ortiz-Reina, Sebastián; Orantes-Casado, Francisco Javier; Acosta-Ortega, Jesús; García‐Solano, José; Pérez‐Guillermo, Miguel

doi:10.1136/jcp.2008.061408

Cited by 23 publications

(21 citation statements)

References 15 publications

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“…Interestingly, a recent study indicated correlation (11), confirming that the ratio of Bcl-2 and Bax is crucial for the apoptosis induced by anticancer agents. In-between HPV-induced cervical cancer and overexpression of cyclin D1 (49). teraction among the Bcl-2 family proteins (Bax, Bak, Bcl-2, Bcl-X, etc.)…”

Section: Tf and Egcg Individually In Hela Cells Resulted In Re-mentioning

confidence: 99%

Tea Polyphenols Induce Apoptosis Through Mitochondrial Pathway and by Inhibiting Nuclear Factor-κB and Akt Activation in Human Cervical Cancer Cells

Singh¹,

Singh²,

Bhui³

et al. 2011

oncol res

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Phytochemicals present in tea, particularly polyphenols, have anticancer properties against several cancer types. However, studies elucidating the role and the mechanism(s) of action of tea polyphenols in cervical cancer are sparse. In this study, we investigated the mechanism of antiproliferative and apoptotic actions exerted by tea polyphenols on human papilloma virus-18-positive HeLa cervical cancer cells. Treatment of green tea polyphenol (-)-epigallocatechin gallate (EGCG) and black tea polyphenol theaflavins (TF) in HeLa cells showed a marked concentration- and time-dependent inhibition of proliferation and induced sub-G1 phase in a dose-dependent manner after 24 h. There was an attenuation of mitochondrial membrane potential with the increase of reactive oxygen species generation, p53 expression, Bax/Bcl-2 ratio, cytochrome-c release, and cleavage of procaspase-3 and -9 and poly(ADP-ribose)-polymerase, indicating the participation of a mitochondria related mechanism. In addition, EGCG as well as TF inhibited activation of Akt and nuclear factor-kappaB (NF-kappaB) via blocking phosphorylation and subsequent degradation of inhibitor of kappaBalpha and kappaBbeta subunits, thereby downregulating cyclooxygenase-2. Additionally, the protein level of cyclin D1, a transcriptional target of NF-kappaB, was also reduced significantly. Thus, we can conclude that tea polyphenols inhibit the growth of cervical cancer cells by inducing apoptosis and regulating NF-kappaB and Akt.

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Section: Tf and Egcg Individually In Hela Cells Resulted In Re-mentioning

confidence: 99%

Tea Polyphenols Induce Apoptosis Through Mitochondrial Pathway and by Inhibiting Nuclear Factor-κB and Akt Activation in Human Cervical Cancer Cells

Singh¹,

Singh²,

Bhui³

et al. 2011

oncol res

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show abstract

“…This tumor is characterized by a well-defined premalignant phase consisting of low-and high-grade SILs (LSIL and HSIL), which facilitates the study of different cofactors and immunohistochemical markers possibly involved in its development [1,18,19]. Transition from LSIL to HSIL is crucial, as approximately 20% of LSIL progress to HSIL [20].…”

Section: Discussionmentioning

confidence: 99%

Association of polymorphism in FcGR3A gene and progression of low-grade precursor lesions of cervical carcinoma

et al. 2010

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“…31,32 The relatively few studies examining ProEx C expression in cervical biopsies have used consensus diagnosis 33,34 or HPV in situ hybridization, 35 with 1 recent study reporting HR-HPV PCR results on a subset of cases. 36 Less work exists regarding anal canal lesions, and most of the published studies regarding p16 and anal biopsies use either consensus diagnosis 37–39 or relatively less sensitive in situ hybridization techniques 40,41 as their “gold standard” for the diagnosis of dysplasia or HR-HPV infection. Only 1 recent study reported PCR results from an assay designed to detect a subset of HPV types.…”

mentioning

confidence: 99%

p16 Is Superior to ProEx C in Identifying High-grade Squamous Intraepithelial Lesions (HSIL) of the Anal Canal

Bala

Pinsky²,

Beck³

et al. 2013

American Journal of Surgical Pathology

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Although the incidence of human papillomavirus (HPV)-associated anal neoplasia is increasing, interobserver and intraobserver reproducibility in the grading of biopsy specimens from this area remains unacceptably low. Attempts to produce a more reproducible grading scheme have led to the use of biomarkers for the detection of high-risk HPV (HR-HPV). We evaluated the performance of standard morphology and biomarkers p16, ProEx C, and Ki-67 in a set of 75 lesions [17 nondysplastic lesions, 23 low-grade squamous intraepithelial lesions (LSIL)/condyloma, 20 high-grade squamous intraepithelial lesions (HSIL), 15 invasive squamous cell carcinomas] from the anal and perianal region in 65 patients and correlated these findings with HPV subtype on the basis of a type-specific multiplex real-time polymerase chain reaction assay designed to detect HR-HPV. A subset of cases with amplifiable HPV DNA was also sequenced. HSIL was typically flat (15/20), and only a minority (4/20) had koilocytes. In contrast, only 1 LSIL was flat (1/23), and the remainder were exophytic. The majority of LSIL had areas of koilocytic change (20/23). HR-HPV DNA was detected in the majority (89%) of invasive carcinomas and HSIL biopsies, 86% and 97% of which were accurately labeled by strong and diffuse block-positive p16 and ProEx C, respectively. LSIL cases, however, only infrequently harbored HR-HPV (13%); most harbored low-risk HPV (LR-HPV) types 6 and 11. Within the LSIL group, p16 outperformed ProEx C, resulting in fewer false-positive cases (5% vs. 75%). Ki-67 was also increased in HR-HPV-positive lesions, although biopsies with increased inflammation and reactive changes also showed higher Ki-67 indices. These data suggest that strong and diffuse block-positive nuclear and cytoplasmic labeling with p16 is a highly specific biomarker for the presence of HR-HPV in anal biopsies and that this finding correlates with high-grade lesions.

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Immunohistochemical evaluation of ProEx C in human papillomavirus-induced lesions of the cervix

Abstract: ProEx C is significantly associated with HPV16 infection and is a useful adjunct in the identification of LGSIL and HGSIL in histological sections when expressed in more than the lower third of the epithelium.

Cited by 23 publications

References 15 publications

Tea Polyphenols Induce Apoptosis Through Mitochondrial Pathway and by Inhibiting Nuclear Factor-κB and Akt Activation in Human Cervical Cancer Cells

Tea Polyphenols Induce Apoptosis Through Mitochondrial Pathway and by Inhibiting Nuclear Factor-κB and Akt Activation in Human Cervical Cancer Cells

Association of polymorphism in FcGR3A gene and progression of low-grade precursor lesions of cervical carcinoma

p16 Is Superior to ProEx C in Identifying High-grade Squamous Intraepithelial Lesions (HSIL) of the Anal Canal

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