scholarly journals Role of p16/INK4a and Ki-67 as specific biomarkers for cervical intraepithelial neoplasia: An institutional study

2017 ◽  
Vol 9 (02) ◽  
pp. 104-110 ◽  
Author(s):  
Ankitha Hebbar ◽  
Venkataramappa Srinivasa Murthy
Keyword(s):  
Diagnostic Accuracy ◽  
Cervical Intraepithelial Neoplasia ◽  
Squamous Metaplasia ◽  
Intraepithelial Neoplasia ◽  
P Value ◽  
Kappa Statistics ◽  
Histopathological Diagnosis ◽  
Ki 67 ◽  
Cervical Biopsy ◽  
P16 Ink4a

Abstract BACKGROUND: P16/INK4a and Ki-67 have emerged as important biomarkers for the detection of high-risk human papilloma virus (HR-HPV) associated dysplastic changes in the cervical biopsy samples. The increasing inter- and intra-observer variability in the diagnosis of dysplastic lesions and immature squamous metaplasia on histopathology has led to the advent of these biomarkers. This study was taken up with an aim to study their role in increasing the diagnostic accuracy in equivocal cases on histopathology. MATERIALS AND METHODS: Fifty cervical biopsy specimens were stained with p16/INK4a and Ki-67 consisting of 10 cases each of cervical intraepithelial neoplasia (CIN I/II/III) along with five cases of squamous metaplasia. Histopathological diagnosis was considered as the gold standard. Statistical analysis was done by kappa statistics, and P value was calculated. RESULTS: The sensitivity and specificity of p16/INK4a and Ki-67 were 76.2%, 87.5%, 90.5%, and 87.5%, respectively. The overall agreement of both the immunostains with histopathological diagnosis was statistically significant (P < 0.05) and the diagnostic accuracy improved when both the stains were used in conjunction. CONCLUSION: Ki-67 and p16/INK4a can be used as complimentary tests in differentiating dysplastic and nondysplastic lesions and help in confirming the histopathological diagnosis. They aid in recognition of dysplasias caused by HR-HPV, which have higher tendency to progress to neoplasia. However, further research is advocated before the widespread use of these markers for screening of dysplasias.

scholarly journals Variability of Pathologists' Utilization of p16 and Ki-67 Immunostaining in the Diagnosis of Cervical Biopsies in Routine Pathology Practice and Its Impact on the Frequencies of Cervical Intraepithelial Neoplasia Diagnoses and Cytohistologic Correlations

2014 ◽  
Vol 138 (1) ◽  
pp. 76-87 ◽  
Author(s):  
Charanjeet Singh ◽  
J. Carlos Manivel ◽  
Alexander M. Truskinovsky ◽  
Kay Savik ◽  
Samy Amirouche ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Lower Range ◽  
Ki 67 ◽  
Detection Rates ◽  
Cervical Biopsy ◽  
Biopsy Specimens ◽  
Frequency Of Use ◽  
Lower Variability ◽  
The Impact

Context.—The use of p16 in cervical biopsies improves the accuracy of cervical intraepithelial neoplasia (CIN) diagnosis and grading and decreases its interpathologist variability. Objective.—To determine the impact of the frequency of use of p16 immunostains in cervical biopsies on pathologists' diagnoses of CIN grade 1 and grade 2 or above (CIN1 and CIN2+) and on cytohistologic correlations. Design.—We identified all cervical biopsy specimens with cytologic correlations subjected or not to p16 staining from January 1, 2005, to September 30, 2010; calculated each pathologist's percentage of p16 use; and correlated it with their major cytohistologic discrepancy rates, CIN2+ diagnoses, and CIN1/CIN2+ ratios. Results.—During the study period, each of the 23 pathologists interpreted 59 to 1811 (mean, 518) of 11 850 cervical biopsy specimens, used p16 for 0% to 21.31% (mean, 10.14%) of these, had CIN2+ detection rates of 9.5% to 24.1% (mean, 18.9%), and CIN1/CIN2+ ratios of 0.7 to 4.5 (mean, 1.5). Compared to the 12 “low users” of p16, who used p16 fewer times than the institution's mean for p16 use, the 11 “high users” of p16 diagnosed more biopsies (8391 versus 3459), had a lower rate of major cytohistologic discrepancies (12.62% versus 14.92%, P &lt; .001), a higher rate of CIN2+ diagnoses (19.9% versus 16.4%, P &lt; .001), a lower range of CIN2+ rates (15.0%–23.1% versus 9.5%–24.1%), and lower CIN1/CIN2+ ratios (1.2 versus 2.3). Conclusions.—We found a high intrainstitutional variability of p16 use in cervical biopsies, CIN2+ rates, and CIN1/CIN2+ ratios. Use of p16 for greater than 10% of cervical biopsies was associated with improved cytohistologic correlation rates and with lower variability in the frequencies of histologic diagnoses.

scholarly journals Evaluation of biomarkers p16ink4a/ki-67 in cervical cytology for diagnosis of cervical intraepithelial neoplasia

2016 ◽  
Author(s):  
P. K. Sathija ◽  
S. Rajaram ◽  
V. K. Arora ◽  
B. Gupta ◽  
N. Goel
Keyword(s):  
Diagnostic Accuracy ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Cervical Cytology ◽  
Low Grade ◽  
Nuclear Staining ◽  
Care Hospital ◽  
High Grade ◽  
Ki 67 ◽  
Good Diagnostic Accuracy

Background: Novel biomarkers, P16INK4a/Ki-67 are disease specific and identify risk of progression to cervical cancer. Aim: To test the clinical utility of biomarkers p16INK4a/Ki-67 in cervical intraepithelial neoplasia. Methodology: Experimental study was conducted over an 18 month period at a tertiary care hospital. 3500 sexually active women between 30-55 years were screened by VIA/VILI, Pap test & HPV-DNA PCR. All screen positive women (n=280) underwent colposcopy and biopsy if required. At the time of colposcopy repeat cervical smear were taken for evaluation of p16INK4a/Ki-67. Immunocytochemistry for p16INK4A and Ki-67 was done by partitioning one slide into two parts for each biomarker. For p16INK4A positivity, nuclear +/- cytoplasmic scoring and intensity score was calculated and final score obtained. For Ki-67 staining was exclusively nuclear. Staining patterns were categorized as negative, intermediate or strongly positive. Results: 86 women with abnormal cytology were evaluated with p16INK4A/Ki-67 immunocytochemistry and 20.9% (n=18) and 18.6% (n=16) were positive for each biomarker. For ASCUS (n=42) and LSIL (n=23) smears, specificity and NPV were 100% with a likelihood ratio (LR+) of 27 and 25 respectively suggesting good diagnostic accuracy. The combined sensitivity and specificity of p16INK4a/Ki-67 in detecting CIN-2+ lesion was 76.9% and 95.8% respectively with LR+ of 18.72 in high grade smears. Conclusions: p16INK4A/Ki-67 evaluation in cervical cytology are valuable biomarkers in ruling out or detecting CIN2+ in ASCUS and LSIL smears. Unnecessary intervention in large number of low grade smears can be avoided by applying these biomarkers. In high grade smears detection rate of biomarkers p16INK4A/Ki-67 was high and had a good diagnostic accuracy.

scholarly journals Human Papillomavirus 16 lineage D is associated with high risk of cervical cancer in the Brazilian Northeast region

2021 ◽  
Author(s):  
Luís Felipe Leite Martins ◽  
Miguel Ângelo Martins Moreira ◽  
Rodrigo Alves Pinho ◽  
Neilane Bertoni ◽  
Shayany Pinto Felix ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
P Value ◽  
Histopathological Diagnosis ◽  
Cross Sectional ◽  
Hpv 16 ◽  
Northeast Region ◽  
Human Papillomavirus 16 ◽  
Cancer Group

Abstract BackgroundLike HPV types, different lineages also appear to have different carcinogenic capabilities. Studies have shown that oncogenic HPV specific to the genotype lineage is associated with different risks for the development of cervical intraepithelial neoplasia (CIN2 / CIN3) and cervical cancer. This study aims to analyze the genetic diversity of HPV 16 genotype in cases of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer in women from the Northeast region of Brazil.Methods and ResultsA cross-sectional hospital-based study conducted in the Northeast region of Brazil from 2014 through 2016. In the sample, there were 196 cases of HPV-16 variant (59 cervical intraepithelial neoplasia - CIN2/CIN3 and 137 cases of cervical cancer). Difference of proportion test was used to compare groups of CIN2/CIN3 and cervical cancer by viral lineage (p-value <0.05) in respect to HPV-16 lineage prevalence.The percentage of lineage frequencies by histopathological diagnosis showed a borderline difference of lineage A in the CIN2/CIN3 group compared to the cervical cancer group (p = 0.053). In relation to lineage D, the proportion was higher in cancer cases (32.8%) compared to the CIN2/CIN3 group (16.9%), p-value of 0.023.ConclusionsHPV16 lineage A was the most frequent in both CIN2/CIN3 and cervical cancer samples, while lineage D predominated in cervical cancer, suggesting a possible association of HPV-16 lineage D with cervical cancer.

The role of immunohistochemistry in the diagnosis of cervical intraepithelial neoplasia of different severity

2016 ◽  
pp. 138-140
Author(s):  
S.I. Zhuk ◽  
◽  
O.A. Taran ◽  
A.N. Koshmienskaya ◽  
T.V. Lobastova ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cervical Intraepithelial Neoplasia ◽  
Precancerous Lesions ◽  
Molecular Genetic ◽  
Intraepithelial Neoplasia ◽  
Reproductive Age ◽  
Moderate Degree ◽  
Ki 67 ◽  
The Third ◽  
Diagnosis And Prognosis

The objective: the finding of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia of different severity to optimize the diagnosis and prognosis of the disease. Patients and methods. The study involved 42 women of reproductive age with cervical intraepithelial the neoplasia of the cervix varying degrees applied to the doctor of cervical pathology Zhitomir regional oncologic dispensary. All women (n=42) were divided into groups. The first group included 15 patients (35.7%) with cervical intraepithelial neoplasia with mild. The second group included 13 women (31%) with cervical intraepithelial neoplasia a moderate degree. The third group was represented by patients with cervical intraepithelial neoplasia with severe – 14 respondents (33.3 per cent). Results. Marker BCL-2 in patients of the first group was positive in 7 patients (46.7%), Smooth Muscule Actin was positive in 9 patients (60%) and Ki-67 was diagnosed in 8 of the surveyed women (53.3%). In the second group of BCL-2 was positive in 8 patients (61.5%), Clone 124, Smooth Muscule Actin, Clone 1A4 was positive in 9 patients (69.2%), and Ki-67 was diagnosed in 12 of the surveyed women (92.3%). Marker BCL-2 in patients of the third group was positive in 12 patients (85.7%), Smooth Muscule Actin was positive in 10 patients (71.4%) and Ki-67 was diagnosed in 13 of the surveyed women (92.9% ). Conclusion. Carcinogenesis is associated with molecular genetic damage to the cervix. Some of the products of this process can be used as prognostic and diagnostic markers of tumor progression. Determination of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia makes it possible to accurately verify the diagnosis and to predict the course of pathological changes in the flat epithelium of the cervix. Key words: cervical intraepithelial neoplasia, cervical cancer, morphological diagnostics of precancerous lesions, BCL-2, Smooth Muscule Actin, Ki-67.

To Determine the Degree of Agreement between Ki67 and Histopathology to Differentiate between Hydatidiform Mole

2021 ◽  
Vol 15 (10) ◽  
pp. 2619-2621
Author(s):  
Mariya Manzoor ◽  
Haseeb Ahmed Khan ◽  
Sabiha Riaz ◽  
Imrana Tanvir ◽  
Atiya Batool Gardezi ◽  
...  
Keyword(s):  
Hydatidiform Mole ◽  
P Value ◽  
Kappa Statistics ◽  
Cross Sectional Survey ◽  
Ki 67 ◽  
Cross Sectional ◽  
Histopathologic Diagnosis ◽  
Hematoxylin And Eosin ◽  
High Degree ◽  
Gross Examination

Aim: To determine the degree of agreement between Ki67 and histopathology to differentiate between hydatidiform mole and hydropic abortus. Methods: Descriptive, Cross Sectional Survey was conducted in the Department of Pathology, Fatima Memorial Hospital, Lahore during 6 months (May 11, 2016 to Nov 11, 2016). Using non-probability consecutive sampling, 105 cases were included in this study as per the inclusion and exclusion criteria. 10% buffered formalin was used to fix the sepecimens. Gross examination and staining with Hematoxylin and Eosin was done. The cases were diagnosed by a histopathologist. IHC staining Ki67 was performed, assessed by histopathologist and the data was recorded on the proforma. Results: The mean age was 27.79±5.81 years with minimum and maximum ages of 18 years and 42 years respectively. The histopathological findings showed hydatidiform mole in 41 (39%) women and hydropic abortus in 64(61%) women. The Ki67 was reported to be >25 in 41(39%) patients and less than or equal to 25 in 64(61%) patients. The agreement of differentiation in the two types for histopathology and Ki67 was found in 101(96.2%) patients. Kappa statistics showed 92% (p-value= 0.000) strength of agreement between histopathology and Ki67. Conclusion: There is high degree of agreement between Ki67 and histopathology for differentiation of hydatidiform mole and hydropic abortus. So Ki67 can be used as an adjacent in histopathologic diagnosis of hydatidiform mole in difficult cases. MeSh words: Hydatidiform Mole, Immunohistochemistry, Ki-67 Antigen

Ki-67 immunoquantitation in cervical intraepithelial neoplasia (CIN): a sensitive marker for grading

2001 ◽  
Vol 193 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Arnold-Jan Kruse ◽  
Jan P. A. Baak ◽  
Peter C. de Bruin ◽  
Mehdi Jiwa ◽  
Wim P. Snijders ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Ki 67 ◽  
Sensitive Marker
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