p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of 796 archival specimens

Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Stephen; Koch, Jørn

doi:10.1186/1746-1596-4-22

Cited by 61 publications

(57 citation statements)

References 30 publications

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“…It is necessary to distinguish normal from CIN of any grade, and benign or lower-grade CIN, which is mostly transient dysplasia (CIN 1), from high-grade CIN. P16 is a preferable substitute indicator for Hr-HPV infection, and its expression in CIN is widely researched and reported [1][2][3][4][5][6][7][8][9][10][12][13][14][15][16][17][18]. According to previous studies [3], p16 showing diffuse strong positivity was highly sensitive to CIN 3 and CIN 2 but insensitive to CIN 1.…”

Section: Discussionmentioning

confidence: 99%

“…When cervical cancer and CIN occur, the HPV E7 proteins cause dysfunction of pRb, causing over-expression of p16 protein yet being unable to control the cell cycle. P16 shows a high rate of positive results in high grade CIN while it shows a low rate of positive results and weak expressions in low grade CIN [9,13,19].…”

Section: Introductionmentioning

confidence: 99%

“…It is often mixed up with reactive/reparative epithelial changes, immature squamous metaplasia, and atrophy [1,4,5]. To increase the accuracy of CIN diagnosis, it is especially necessary and significant to use biomarkers as an objective indicator to help in histopathological diagnoses of CIN [3,[6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…P16 INK4a (p16) is a kind of anti-oncogene and considered as a preferable substitute marker for Hr-HPV infection [1][2][3][4][5][6][7][8][9][10][12][13][14][15][16][17][18]. As a cyclin-dependent kinase inhibitor, p16 competes with cyclin D1 to combine with CDK4/6 and specifically suppresses the activity of CDK4, inhibiting the CDK-induced phosphorylation of pRb and arresting the cell transition from G1 phase to S phase, thereby playing a role in feedback control of mitosis.…”

Section: Introductionmentioning

confidence: 99%

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A cocktail of MCM2 and TOP2A, p16 INK4a and Ki-67 as biomarkers for the improved diagnosis of cervical intraepithelial lesion

Yang

Zhu²,

Liou³

et al. 2013

pjp

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The purpose of this paper was to explore the immunohistochemistry (IHC) results for a cocktail of minichromosome maintenance protein 2 (MCM2) and topoisomerase IIα (TOP2A), p16 INK4a and Ki-67 as biomarkers for the diagnosis of cervical intraepithelial neoplasia (CIN), improving the routine interpretation of cervical histopathology. 133 cases of CIN were collected from the archival data. All routine hematoxylin and eosin (HE)-stained slides of the subjects were re-examined independently by three senior pathologists, to provide a "consensus diagnosis". Immunohistochemistry for the three biomarkers was performed, and the results were reviewed independently of the corresponding archival diagnosis to make a "diagnosis assisted by IHC" by the original pathological practitioners. The diagnosis accordance rate of the archival original diagnosis with the "consensus diagnosis" and the "diagnosis assisted by IHC" with the "consensus diagnosis" were verified by Fisher's exact test. The results showed that raw agreement between the original HE diagnosis and the "consensus diagnosis" was 88.55%, and raw agreement between the "diagnosis assisted by IHC" and the "consensus diagnosis" was 95.78%. The latter was significantly higher than the former (Fisher's exact test, p = 0.023). In conclusion, the three biomarkers had a high degree of sensitivity and specificity, and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis, and reduce inter-observer variability in cervical biopsy specimens.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A cocktail of MCM2 and TOP2A, p16 INK4a and Ki-67 as biomarkers for the improved diagnosis of cervical intraepithelial lesion

Yang

Zhu²,

Liou³

et al. 2013

pjp

View full text Add to dashboard Cite

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“…Second, the method of detection for HPV status was suboptimal in all included studies. HPV testing through measuring HPV E6 expression or p16 overexpression is ideal because this will identify HPV positivity in women with functionally active HPV (37,38). However, all reports included in this meta-analysis evaluated HPV status using DNA-based approaches (e.g., PCR, hybrid capture), which are very sensitive approaches (39), but do not necessarily show the presence of functionally active HPV.…”

Section: Subtotal (95% Ci)mentioning

confidence: 99%

p53 Arg72Pro Polymorphism, HPV Status and Initiation, Progression, and Development of Cervical Cancer: A Systematic Review and Meta-Analysis

Habbous

Pang

Eng

et al. 2012

Clinical Cancer Research

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Cervical cancer develops through progression from normal cervical epithelium through squamous intraepithelial lesions (SIL) to invasive cancer. Cervical cancer is associated with oncogenic human papillomavirus (HPV). The HPV E6 oncoprotein binds to the tumor suppressor gene product p53, promoting its degradation; the Arg allele of p53 Arg72Pro polymorphism binds more ardently with HPV E6 than the Pro variant. Here we evaluate the role of p53 Arg72Pro polymorphism and HPV status on the initiation, progression, and development of cervical cancer. A systematic review and meta-analysis were conducted. Events of interest were the initiation of neoplasia (SIL vs. normal), progression to invasive cancer (cervical cancer vs. SIL), and risk of invasive cancer (cervical cancer vs. normal) by HPV status. OR were extracted from individual studies and pooled using generic inverse variance and random effects modeling. Forty-nine studies were included. In individuals showing HPV positivity, there was a significantly higher odds of progression from SIL to cervical cancer with the p53 Arg allele [OR 1.37; 95% confidence intervals (CI), 1.15-1.62; P < 0.001]. This association was not seen in HPVnegative individuals. p53 Arg72Pro was not associated with the risk of cervical cancer or initiation of SIL in either HPV-positive or HPV-negative patient subsets. The Arg variant of p53 Arg72Pro is associated with progression of SIL to cervical cancer only in the presence of HPV positivity. There were no associations of this variant with overall risk or initiation of cancer in either HPV-positive or HPVnegative patients.

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Poorly differentiated squamous cell carcinoma of the cervix with sarcomatoid differentiation: Report of a case with cytohistological correlation

Akhtar

Flowers

Nuttli

et al. 2016

Diagnostic Cytopathology

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Sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix is a rare malignancy with uncertain pathogenesis and aggressive clinical behavior. The diagnosis of this tumor poses a challenge to the cytopathologist since accurate diagnosis is based on identification of two malignant components, that is, epithelial and sarcomatoid. Most cases usually lack the sarcomatoid component on Papanicolaou test (Pap test). Therefore, a poorly differentiated carcinoma or malignant neoplasm is the most often rendered diagnosis. To date, less than 20 cases have been reported. Most of these cases were diagnosed by histopathologic findings. To our knowledge, cytomorphologic findings of SSCC on a liquid-based Pap test, with utility of cell block sections, in recognition of the two components of tumor, with follow-up histopathologic correlation have not been described. A case of SSCC occurring in a 57-year-old postmenopausal woman, describing the cytologic features on a liquid-based Pap-test, histopathologic findings of subsequent cervical biopsy, differential diagnosis, and role of ancillary studies are illustrated and discussed. Diagn. Cytopathol. 2017;45:137-142. © 2016 Wiley Periodicals, Inc.

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p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of 796 archival specimens

Abstract: Background: To evaluate the usefulness of this biomarker in the diagnosis of cases of cervical neoplasia we studied the immunohistochemical expression of p16 INK4a in a large series of archival cervical biopsies arranged into tissue microarray format.

Cited by 61 publications

References 30 publications

A cocktail of MCM2 and TOP2A, p16 INK4a and Ki-67 as biomarkers for the improved diagnosis of cervical intraepithelial lesion

A cocktail of MCM2 and TOP2A, p16 INK4a and Ki-67 as biomarkers for the improved diagnosis of cervical intraepithelial lesion

p53 Arg72Pro Polymorphism, HPV Status and Initiation, Progression, and Development of Cervical Cancer: A Systematic Review and Meta-Analysis

Poorly differentiated squamous cell carcinoma of the cervix with sarcomatoid differentiation: Report of a case with cytohistological correlation

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