Survivin and Telomerase Expression in the Uterine Cervix of Women With Human Papillomavirus-Induced Lesions

Barbosa, Lyliana Coutinho Resende; Silva, Ismael Dale Cotrim Guerreiro da; Correa, José Carlos Bencomo; Ribalta, Julisa Chamorro Lascasas

doi:10.1097/igc.0b013e318203d42b

Cited by 20 publications

(25 citation statements)

References 21 publications

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“…Similar findings were reported by Barbosa (2011) andBranca (2008), in which survivin expression was reported to be increased in accordance with tumor progressivity. Therefore, higher grade lesions have higher levels of survivin expression.…”

Section: Discussionsupporting

confidence: 88%

Scoring System and Management Algorithm Assessing the Role of Survivin Expression in Predicting Progressivity of HPV Infections in Precancerous Cervical Lesions

Indarti

Aziz²,

Suryawati³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 88%

Scoring System and Management Algorithm Assessing the Role of Survivin Expression in Predicting Progressivity of HPV Infections in Precancerous Cervical Lesions

Indarti

Aziz²,

Suryawati³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…The list of candidates who have shown potential utility in cervical cancer screening includes p16 INK4a (CDKN2A), survivin (BIRC5), metalloproteinase 9 (MMP9), topoisomerase 2 alpha (TOP2A), minichromosome maintenance 5 (MCM5), or MKi67 proteins (MKI67). [7][8][9] Most studies focused on these biomarkers have used immunohistochemistry to detect protein expression. However, several shortcomings of immunohistochemistry, in particular the interobserver variation inherent to all morphological techniques and the difficulty to obtain reproducible quantification, hamper proper evaluation of the clinical usefulness of these biomarkers.…”

mentioning

confidence: 99%

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Pino

Svanholm-Barrie²,

Torné

et al. 2015

Modern Pathology

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Several high-risk human papillomavirus (HPV)-induced cell biomarkers have been proposed as possible candidates to identify patients harboring high-grade squamous intraepithelial lesions (HSILs) of the uterine cervix. We aimed to determine the feasibility of the detection of the mRNA of six biomarkers in cervical smear specimens obtained by liquid-based cytology and to evaluate whether this approach might be useful in the identification of patients with HSIL. One-hundred and twenty three women referred to colposcopy in the Hospital Clinic of Barcelona were included in the study. After a thorough study, including Pap test, high-risk HPV testing (Hybrid Capture 2 test), and colposcopy with directed biopsy and/or endocervical curettage, 48 patients were diagnosed with HSIL, whereas 75 were classified as negative (n ¼ 28), or harboring low-grade SIL (n ¼ 47). CDKN2A/p16, BIRC5, MMP9, TOP2A, MCM5, and MKI67 mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction in liquid-based cytology after the Pap test and Hybrid Capture 2 performance. The tissue expression of these biomarkers was analyzed by immunohistochemistry in the biopsy material. One-hundred and thirteen out of 123 (92%) liquid-based cytology yielded adequate material for mRNA analysis. TOP2A was the most sensitive (97%) biomarker for the detection of HSIL and CDKN2A/p16 the most specific (78%). The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 96% (95% confidence interval (CI): 88-99) and a specificity of 71% (95% CI: 55-82). In the immunohistochemistry analysis, all biomarkers showed a high sensitivity but low specificity for HSIL, except CDKN2A/p16 which had a sensitivity of 100% and a specificity of 63%. The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 100% (95% CI: 91-100) and a specificity of 43% (95% CI: 32-55). The detection of mRNA of cell biomarkers in liquid-based cytology material is feasible. The combination TOP2A and CDKN2A/p16 has a good balance between sensitivity and specificity for the detection of women with HSIL. Modern Pathology (2015) 28, 312-320; doi:10.1038/modpathol.2014.106; published online 5 September 2014Screening programs based on cervical cytology (Pap test) have led to a decrease in the incidence and the mortality by cervical cancer. However, the efficacy of cytological screening is hampered by the suboptimal sensitivity and interobserver variability of the conventional Pap test. 1,2 Although the introduction of liquid-based cytology has not led to improvements in terms of relative sensitivity for the detection of cervical cancer precursors, 3 this technique has enabled the use of adjunctive tests that may help to reduce the rate of false-negative cytological results and add objectivity to the classical morphological evaluation.High-risk human papillomaviruses (HPV) are the causative agents of cervical cancer, and high-risk HPV testing has shown to improve the sensitivity of the Pap test to over 95%. 4,5 However, high-risk HPV tests have a lower specificity than...

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“…A large number of biomarkers have been identified that are overexpressed in cervical cancer cells with potential for cervical cancer screening, such as p16 INK4A , Ki-67, Cyclin E, p53, and survivin, among others [5][6][7]. P16 INK 4A is a tumor suppressor protein which is induced in cells upon expression of high-risk HPV E7 protein [8] and several reports indicate that overexpression of p16 is associated with the process of carcinogenesis in the cervical epithelium [9].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Dadlani¹,

López²,

Fern³

et al. 2016

J Cancer Sci Ther

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Objective: Cervical cancer is the second most common cancer in women with high rates of mortality worldwide. Cervical cancer is slowly progressive and is preceded by pre-invasive intraepithelial lesions. Therefore, detection of premalignant lesions is key to preventing disease progression to advanced stages. The objective of the present study was examination and quantification of the differentially expressed non-coding mitochondrial RNAs during progression of disease. Material and methods:The differential expression of S-ncmtRNA and AS-ncmtRNA was analyzed by in situ hybridization (ISH) using tissue macroarrays (TMA) from normal, CIN1, CIN2, CIN3 and invasive squamous carcinoma (SCC). PCNA and p16INK-4a were detected in consecutive biopsies by immunohistochemistry. Quantification of ISH signal was carried out with Image ProPlus 6.1 software and the results were expressed as percentage of Integrated Optical Density (IOD). Results:We found a marked down-regulation of AS-ncmtRNA in 95% of tissues analyzed (CIN 1/2, CIN 3, and invasive squamous cancer). Moreover, differential expression of ASncmtRNA v/s S-ncmtRNA showed significant difference. Normal proliferating tissues did not display down-regulation of AS-ncmtRNA. Down regulation of ASncmtRNA correlated with the expression of the tumor suppressor protein p16INK-4a Conclusions:We found down-regulation of AS-ncmtRNA in pre-malignant and tumor samples which could distinguish normal tissues from early lesions and tumor samples. These results suggest that the down-regulation of AS-ncmtRNA is a novel marker of early lesions and cervix neoplasia. Previously, we reported that human cells express a unique family of mitochondrial long ncmtRNAs (ncmtRNAs) [12,13]. One of these transcripts, named sense ncmtRNA (SncmtRNA) is expressed in normal proliferating cells and tumor cells but not in resting cells, suggesting a functional role in cell cycle progression [12]. Normal proliferating cells express, in addition to the S-ncmtRNA, two antisense mitochondrial ncmtRNAs (AS-ncmtRNA-1 and AS-ncmtRNA-2) where both AS-ncmtRNAs are down-regulated in human cancer cells regardless of tissue of origin. In order to analyze the expression pattern of these ncmtRNAs in cervical cancer, we performed a qualitative pilot study in cervical biopsies encompassing the progression of the disease. We found that AS-ncmtRNAs are down-regulated in mild, moderate and severe neoplasia and in invasive cervical carcinoma [14]. In the present study a quantitative analysis of the differential expression of the S-ncmtRNA and the ASncmtRNAs was performed in biopsies of CIN1 to CIN3 and invasive cervical carcinoma, correlating it with the expression of the tumor suppressor p16 Assessment of the Expression of LongINK 4A and proliferating cell nuclear antigen (PCNA). Methods Tissue specimensAll the tissues were purchased from Pantomics Inc. (Richmond, CA, USA), corresponding to Tissue Macroarrays (TMA) containing normal cervix, CIN1, CIN2, CIN3 and invasive squamous carcinoma (SCC). For normal specimens,...

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Survivin and Telomerase Expression in the Uterine Cervix of Women With Human Papillomavirus-Induced Lesions

Cited by 20 publications

References 21 publications

Scoring System and Management Algorithm Assessing the Role of Survivin Expression in Predicting Progressivity of HPV Infections in Precancerous Cervical Lesions

Scoring System and Management Algorithm Assessing the Role of Survivin Expression in Predicting Progressivity of HPV Infections in Precancerous Cervical Lesions

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

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