Evaluation of Expression of Apoptosis-Related Proteins and Their Correlation with HPV, Telomerase Activity, and Apoptotic Index in Cervical Cancer

Singh, Amandeep; Sharma, Himani; Salhan, Sudha; Gupta, Subhash; Bhatla, Neerja; Jain, Shreyans; Singh, Neeta

doi:10.1159/000081727

Cited by 24 publications

(21 citation statements)

References 75 publications

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“…KAI1 is a cell surface glycoprotein that participates in cell adhesion regulation and impedes tumor cell separation, thereby inhibiting tumor metastasis. CD82 gene expression is downregulated in the early stages of cervical cancer (Wang et al, 2001;Singh et al, 2004). In this study, we investigated the relationship between the expression levels of three proteins and the various clinicopathologic characteristics of cervical cancer by comparing them at different stages of the cancer: normal tissue, chronic cervicitis, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis

Zhou¹,

Wang²

2015

Genet. Mol. Res.

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ABSTRACT. Cervical cancer is associated with abnormal expression of multiple genes. Survivin and Bcl-2 proteins are apoptosis inhibitors. The tumor suppressor gene CD82, which encodes the protein KAI1, is downregulated in cervical cancer, and is associated with differentiation degree. We investigated the expression levels of three proteins and their correlation with metastasis in cervical cancer by comparing them in different cervical lesions. Immunohistochemistry was used to detect their three protein expression levels in the normal cervix, chronic cervicitis, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. The relationships between the protein expression levels and tumor type, clinical stage, tissue differentiation, invasion, and metastasis were analyzed. Survivin and Bcl-2 expression levels in cervical cancer were significantly higher than in the normal cervix, chronic cervicitis, or CIN (P < 0.05). KAI1 expression was markedly lower in cervical cancer than in the normal cervix, chronic cervicitis, or CIN (P < 0.05). There was no statistical difference between the expression levels of the three proteins in CIN and chronic cervicitis, but there were differences in expression between CIN and normal cervical tissues (P < 0.05). Bcl-2 and survivin levels were positively correlated while KAI1 expression was negatively correlated with clinical stage. Survivin and KAI1 expression levels were associated with lymph node metastasis (P < 0.05), and KAI1 expression was positively related with differentiation degree (P < 0.05). Survivin, Bcl-2, and KAI1 are metastasis-related factors in cervical cancer. Overexpression of survivin and Bcl-2, and low expression of KAI1 promotes cervical cancer progress and metastasis.

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Section: Introductionmentioning

confidence: 99%

Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis

Zhou¹,

Wang²

2015

Genet. Mol. Res.

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“…11 Telomerase has been described as a potential marker for the detection of circulating ovarian tumor cells. 23 In our study higher telomerase activity was seen in ovarian tumors than normal controls as reported in a recent study.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptotic cells were identified by the Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique using the Dead End Colorimetric Cell Death Detection kit (Promega Inc., USA) as previously described. 11 Telomerase assay. Telomerase assay was done on 25 tumors and 10 normal controls as described previously, using the PCR ELISA kit from Roche Diagnostics, GmbH, Germany and following the manufacturer's guidelines.…”

Section: Methodsmentioning

confidence: 99%

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Role of apoptotic regulators in human epithelial ovarian cancer

Kar

Sen²,

Singh³

et al. 2007

Cancer Biology & Therapy

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“…Previous studies have shown that p53 and Bcl2 are effective in the progression of in situ lesions towards invasive SCC (24); it is possible that the predominance of the Bcl2 anti-apoptotic factor effect over the Bax apoptotic factor may be responsible for development of the carcinogenesis process (4,24) . Furthermore, recent studies have shown that the alteration of additional factors with a crucial role in cell cycle progression, telomerase maintenance, apoptosis and chromosomal stability are also equally important in malignant transformations (25).…”

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confidence: 99%

Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

Ayatollahi¹,

Sharifi²,

Sadeghian³

et al. 2014

Balkan Med J

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Squamous cell carcinoma (SCC) of the cervix is one of the most frequent female genital tract cancers, which causes a high level of malignancy-related mortality, affecting a large population worldwide. All of the effects of Human papilloma virus (HPV) infection, which is an important aetiological factor in the development of cervical carcinoma, remain to be clarified completely (1). Compared to studies focused on high risk HPVs in squamous cell carcinoma of the cervix, there are few studies about the mechanisms of carcinogenesis in cervical SCCs lacking HPV.There are about 40 subtypes of HPV affecting the genital tract, some of them have a high association with SCC of the cervix (2). Although more than 20 types of HPV have been found in these tumours, 4 types are responsible for more than 80% of cases (3, 4) and HPV 16 is the most frequent. HPV 16 and 18 are the most oncogenic and virulent types, and altogether are responsible for 70% of uterine cervix cancer (5, 6). Sexual intercourse is the main route of transmission of HPV infection; the frequency of HPV infection in different populations and countries varies widely (7). High risk HPVs, especially HPV 16 and 18, probably impose their early carcinogenesis effect by impairing the cell cycle through modulation of different genes' expression, including E6/E7 proteins (8). These early proteins, E6 and E7, bind and inactivate a tumoursuppressor gene product, p53, and the retinoblastoma tumoursuppressor protein, respectively. In cervical lesions caused by HPVs, the increased proliferation of suprabasal epithelial cells is attributed to the expression of the viral oncogenes, E6 and E7. E7 associates with Rb protein and other members of the pocket protein family, and disrupts the association Background: Human papillomavirus (HPV) infection is an important aetiological factor in squamous cell carcinoma (SCC) of the cervix. Limited studies have been focused on the differences between carcinogenesis of SCCs with and without HPV infection. Aims: The main goal of this study is to determine the expression of some of the apoptotic pathway regulators, including P53, Bax and Bcl2 in SCCs with and without high risk HPV 16/18 infection. Study Design: Cross sectional study. Methods: A total of 42 paraffin-embedded blocks with the histopathological diagnosis of invasive SCC with determined HPV 16/18 status were selected; half of them were HPV positive and the rest were negative. Afterwards, immunohistochemistry stained slides for p53, Bcl2 and Bax were evaluated with H-score, multiplicative and Additive Quick score by two pathologists; in cases of controversy about the results, the mean results were recorded. Results:Mean results and percentage of expression of our three markers were significantly higher in the HPV 16/18 infected group than in uninfected individuals: Respectively, the mean score for Bcl2, Bax and p53 staining according to H-scoring method was 68.5, 234, 106.4 in the HPV 16/18 infected group and 4.5, 218.8, 5.07 in the uninfected group; and the Multiplicative Quick ...

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Evaluation of Expression of Apoptosis-Related Proteins and Their Correlation with HPV, Telomerase Activity, and Apoptotic Index in Cervical Cancer

Cited by 24 publications

References 75 publications

Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis

Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis

Role of apoptotic regulators in human epithelial ovarian cancer

Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

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