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

Singh, Charanjeet; Truskinovsky, Alexander M.; Savik, Kay; Amirouche, Samy; Holler, Jana; Thyagarajan, Bharat; Gulbahce, H. Evin; Pambuccian, Stefan E.

doi:10.5858/arpa.2012-0472-oa

Cited by 16 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aside from the added cost for limited or no benefit to women diagnosed with CIN1, p16 IHC testing of biopsies diagnosed as CIN1 might result in incorrect, overinterpretation of a positive p16 IHC result as CIN2, which could then lead to unnecessary treatment and a concomitant increased risk of preterm delivery for those still considering childbearing. 13,14,42 Limited p16 IHC testing, and/or possibly Ki-67 IHC testing, of some CIN1 might have some value for internal use as a laboratory quality control standard, 7,44 similar to the use of HPV to squamous intraepithelial lesion ratios for cytology, 45 to set the threshold of normal versus nonnormal histology. We observed that approximately one-quarter of the CP-diagnosed CIN1 tested p16 IHC positive in this study.…”

Section: Discussionmentioning

confidence: 99%

Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology

Castle¹,

Adcock²,

Cuzick³

et al. 2019

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.— Lower Anogenital Squamous Terminology (LAST) standardization recommended p16INK4a immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs). Objective.— To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses. Design.— A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available. Results.— Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall ( Ptrend ≤ .001) and within each HPV risk group ( Ptrend ≤ .001 except for low-risk HPV [ Ptrend < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group ( Ptrend < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies ( P < .001). p16 IHC–positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL+ cytology, or to be diagnosed as CIN3+ by the EP ( P < .001 for all). p16 IHC–positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC–negative, CP-diagnosed CIN2 biopsies ( P < .001). Conclusions.— p16 IHC–positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of “HSIL” diagnosis, which includes p16 IHC–positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.

show abstract

Section: Discussionmentioning

confidence: 99%

Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology

Castle¹,

Adcock²,

Cuzick³

et al. 2019

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

show abstract

“…The histologic evaluation of p16 INK4A and Ki–67 improves diagnostic accuracy [ 26 ]; dual staining was introduced mainly to increase the reproducibility and specificity of stand–alone p16 INK4A staining. Regardless of HPV status, diffuse p16 INK4A immunostaining is a hallmark of high-grade squamous intraepithelial lesions [ 27 ] and is an efficient screening tool [ 28 ]. Several candidate biomarkers and combinations thereof are being explored to predict the transition step [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Mathematical Modelling of Cervical Precancerous Lesion Grade Risk Scores: Linear Regression Analysis of Cellular Protein Biomarkers and Human Papillomavirus E6/E7 RNA Staining Patterns

et al. 2023

View full text Add to dashboard Cite

The current practice of determining histologic grade with a single molecular biomarker can facilitate differential diagnosis but cannot predict the risk of lesion progression. Cancer is caused by complex mechanisms, and no single biomarker can both make accurate diagnoses and predict progression risk. Modelling using multiple biomarkers can be used to derive scores for risk prediction. Mathematical models (MMs) may be capable of making predictions from biomarker data. Therefore, this study aimed to develop MM–based scores for predicting the risk of precancerous cervical lesion progression and identifying precancerous lesions in patients in northern Thailand by evaluating the expression of multiple biomarkers. The MMs (Models 1–5) were developed in the test sample set based on patient age range (five categories) and biomarker levels (cortactin, p16INK4A, and Ki–67 by immunohistochemistry [IHC], and HPV E6/E7 ribonucleic acid (RNA) by in situ hybridization [ISH]). The risk scores for the prediction of cervical lesion progression (“risk biomolecules”) ranged from 2.56–2.60 in the normal and low–grade squamous intraepithelial lesion (LSIL) cases and from 3.54–3.62 in cases where precancerous lesions were predicted to progress. In Model 4, 23/86 (26.7%) normal and LSIL cases had biomolecule levels that suggested a risk of progression, while 5/86 (5.8%) cases were identified as precancerous lesions. Additionally, histologic grading with a single molecular biomarker did not identify 23 cases with risk, preventing close patient monitoring. These results suggest that biomarker level–based risk scores are useful for predicting the risk of cervical lesion progression and identifying precancerous lesion development. This multiple biomarker–based strategy may ultimately have utility for predicting cancer progression in other contexts.

show abstract

“…Ideally, the use of IHC stains should allow for accurate determination of the nature of atypical cells, facilitating a definitive diagnosis and thereby reducing the rate of indeterminate, equivocal or “nondefinitive” diagnoses . The use and utility of IHC stains has been explored recently in various areas of pathology, including autopsy pathology, surgical pathology, urologic pathology, gynecologic pathology, dermatopathology, and hepatic pathology . To our knowledge, however, there are no prior studies systematically exploring the use and utility of IHC stains in current routine cytopathology of body fluids.…”

Section: Introductionmentioning

confidence: 99%

The utilization and utility of immunostains in body fluid cytology

Alshaikh

Lapadat

Atieh

et al. 2020

Cancer Cytopathology

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Body fluid cytology (BFC) is an important tool in the diagnosis and staging of malignancy and is aided by the judicious use of immunohistochemistry (IHC). The aim of this study was to determine the usage rates of IHC stains in BFC, their type and indications, and their diagnostic impact. We also attempted to estimate the optimal rate of IHC use in BFC by comparing the entire laboratory's and each individual cytopathologist's IHC use rates with their respective indeterminate and malignant diagnosis rates. METHODS: We conducted a retrospective study of IHC stain use in BFC during a 5.5-year interval (2013-2018) and determined the laboratory's and each individual cytopathologist's IHC usage patterns according to the final diagnosis, site, and indications for their use. RESULTS: A total of 477 out of 4144 (11.5%) BFC cases had 2128 individual immunostains performed, with an average of 4.5 immunostains per case. Individual cytopathologists usedIHC stains on 6.7% to 22% of their BFC cases. Pathologists with higher rates of IHC stain use than the laboratory's mean were less experienced and had higher rates of indeterminate but not of malignant diagnoses. The most common indication for the use of IHC stains was differentiating mesothelial from malignant cells. MOC31, calretinin, Ber-EP4, CD68, and D2-40 were the most commonly used of the 67 different IHC stains used in BFC. CONCLUSIONS: The laboratory's mean may represent the optimal IHC use rate, as higher IHC use rates did not lead to more diagnostic certainty or higher pickup rates of malignant cells. Cancer Cytopathol 2020;128:384-391.

show abstract

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

Cited by 16 publications

References 50 publications

Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology

Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology

Mathematical Modelling of Cervical Precancerous Lesion Grade Risk Scores: Linear Regression Analysis of Cellular Protein Biomarkers and Human Papillomavirus E6/E7 RNA Staining Patterns

The utilization and utility of immunostains in body fluid cytology

Contact Info

Product

Resources

About