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

2019 ◽  
Vol 144 (6) ◽  
pp. 725-734 ◽  
Author(s):  
Philip E. Castle ◽  
Rachael Adcock ◽  
Jack Cuzick ◽  
Nicolas Wentzensen ◽  
Norah E. Torrez-Martinez ◽  
...  

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.

2007 ◽  
Vol 17 (6) ◽  
pp. 1205-1214 ◽  
Author(s):  
M. I. Rosa ◽  
L. R. Medeiros ◽  
M. C. Bozzetti ◽  
J. Fachel ◽  
E. Wendland ◽  
...  

The detection of telomerase activity in cervix may provide information on cervical carcinogenesis and may be a marker to monitor cervical intraepithelial neoplasia transition. A quantitative systematic review was performed to estimate the accuracy of telomerase assay in cervical lesions. Studies that evaluated the telomerase test (telomerase repeated amplification protocol) for the diagnosis of cervix lesions and compared it to paraffin-embedded sections as the diagnostic standard were included. Ten studies were analyzed, which included 1069 women. The diagnostic odds ratio (DOR) for a positive telomerase test for low-grade squamous intraepithelial lesions (Lo-SIL) vs normal or benign lesions was 3.2 (95% CI, 1.9–5.6). The DOR for a positive telomerase test for high-grade squamous intraepithelial lesions (Hi-SIL) vs Lo-SIL, normal or benign lesions was 5.8 (95% CI, 3.1–10). For cervix cancer vs Hi-SIL, the DOR for a positive telomerase test was 8.1 (95% CI, 3.2–20.3) and for cervix cancer vs Lo-SIL, normal or benign lesions, it was 40.9 (95% CI, 18.2–91). Our data support the current hypothesis that telomerase may activate an early event in cervical carcinogenesis that could be associated with the initiation and progression of cervical lesions


Author(s):  
Yuxin Liu ◽  
W Glenn McCluggage ◽  
Teresa M Darragh ◽  
Wenxin Zheng ◽  
Jennifer M Roberts ◽  
...  

Abstract Objectives: The Lower Anogenital Squamous Terminology (LAST) recommendations classify human papillomavirus–associated squamous lesions into low- and high-grade squamous intraepithelial lesions (LSILs/HSILs). Our study aimed to assess interobserver agreement among 6 experienced pathologists in assigning 40 anal lesions previously diagnosed as anal intraepithelial neoplasia 2 (AIN 2) to either HSIL or non-HSIL categories. Methods: Agreement based on photomicrographs of H&E alone or H&E plus p16 immunohistochemistry was calculated using κ coefficients. Results: Agreement was fair based on H&E alone (κ = 0.42; 95% confidence interval [CI], 0.34-0.52). Adding p16 improved agreement to moderate (κ = 0.55; 95% CI, 0.54-0.62). On final diagnosis, 21 cases (53%) had unanimous diagnoses, and 19 (47%) were divided. When designating p16 results as positive or negative, agreement was excellent (κ = 0.92; 95% CI, 0.83-0.95). Among variables (staining location, extent, and intensity), staining of the basal/parabasal layers was a consistent feature in cases with consensus for positive results (20/20). Of the 67 H&E diagnoses with conflicting p16 results, participants modified 32 (48%), downgrading 23 HSILs and upgrading 9 non-HSILs. Conclusions: Although p16 increased interobserver agreement, disagreement remained considerable regarding intermediate lesions. p16 expression, particularly if negative, can reduce unwarranted HSIL diagnoses and unnecessary treatment.


PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0190156 ◽  
Author(s):  
Sonia Andersson ◽  
Karen Belkić ◽  
Selin Safer Demirbüker ◽  
Miriam Mints ◽  
Ellinor Östensson

2021 ◽  
Vol 12 ◽  
Author(s):  
Zijin Xiang ◽  
Xueru Chen ◽  
Qiaoli Lv ◽  
Xiangdong Peng

BackgroundAs immunotherapy has received attention as new treatments for brain cancer, the role of inflammation in the process of glioma is of particular importance. Increasing studies have further shown that long non-coding RNAs (lncRNAs) are important factors that promote the development of glioma. However, the relationship between inflammation-related lncRNAs and the prognosis of glioma patients remains unclear. The purpose of this study is to construct and validate an inflammation-related lncRNA prognostic signature to predict the prognosis of low-grade glioma patients.MethodsBy downloading and analyzing the gene expression data and clinical information of the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) patients with low-grade gliomas, we could screen for inflammatory gene-related lncRNAs. Furthermore, through Cox and the Least Absolute Shrinkage and Selection Operator regression analyses, we established a risk model and divided patients into high- and low-risk groups based on the median value of the risk score to analyze the prognosis. In addition, we analyzed the tumor mutation burden (TMB) between the two groups based on somatic mutation data, and explored the difference in copy number variations (CNVs) based on the GISTIC algorithm. Finally, we used the MCPCounter algorithm to study the relationship between the risk model and immune cell infiltration, and used gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the enrichment pathways and biological processes of differentially expressed genes between the high- and low-risk groups.ResultsA novel prognostic signature was constructed including 11 inflammatory lncRNAs. This risk model could be an independent prognostic predictor. The patients in the high-risk group had a poor prognosis. There were significant differences in TMB and CNVs for patients in the high- and low-risk groups. In the high-risk group, the immune system was activated more significantly, and the expression of immune checkpoint-related genes was also higher. The GSEA, GO, and KEGG analyses showed that highly expressed genes in the high-risk group were enriched in immune-related processes, while lowly expressed genes were enriched in neuromodulation processes.ConclusionThe risk model of 11 inflammation-related lncRNAs can serve as a promising prognostic biomarker for low-grade gliomas patients.


2004 ◽  
Vol 22 (9) ◽  
pp. 1736-1742 ◽  
Author(s):  
A. Liljegren ◽  
G. Lindgren ◽  
Y. Brandberg ◽  
S. Rotstein ◽  
B. Nilsson ◽  
...  

Purpose To evaluate the psychological consequences of genetic counseling followed by a surveillance program using colonoscopy among individuals with increased risk of colorectal cancer. Patients and Methods Two hundred sixty-five individuals, participating in a surveillance program with colonoscopy, were mailed a survey questionnaire that assessed their experience of the surveillance program and their perception of the risk of colorectal cancer. The Hospital Anxiety and Depression scale and the Swedish Short Form-36 Health Survey was also included. Results Two hundred forty individuals completed the questionnaire and were divided into the following risk groups: risk group 1, an individual with a mutation in hMLH1 or hMSH2 and a lifetime colorectal cancer risk of 80% (n = 28); risk group 2, a lifetime colorectal cancer risk of 40% (n = 129); and risk group 3, a lifetime colorectal cancer risk of 20% (n = 83). Among all individuals, the mean for perceived benefit was 8.0, and the perception of discomfort was 3.3 on the visual analog scale (1-10). In risk group 1, 61% underestimated personal risks as being 40% or less. Approximately 50% of the subjects in risk groups 2 and 3 either under- or overestimated their lifetime risk. According to the Swedish Short Form-36 Health Survey and the Hospital Anxiety and Depression scale, the study sample resembled the reference population. Conclusion A majority of the study sample understood why they were under surveillance, and regular colonoscopies were well-tolerated. The wide range of risk perception as well as low-risk perception in mutation positive subjects is acceptable, as long as these individuals adhere to surveillance programs and do not demonstrate increased levels of anxiety or depression.


2017 ◽  
Vol 16 (1) ◽  
pp. 3-7
Author(s):  
Ratna Adhikari Khatri ◽  
Lee Budhathoki ◽  
Arya Rana Pande ◽  
Sadikshya Singh

Introduction: Cervical cancer is one of the most common cancers in the world. It is the most common cancer among females in Nepal. Progression of pre-invasive precursor lesions called Cervical Intraepithelial Neoplasia (CIN) can result in invasive cancer over years and decades. Papanicolaou smear can detect these lesions early. The aim of this paper is to study the prevalence of abnormal Pap smear test and report the results.Methods: Observational study of Pap smear of 1100 women of age 21 to 65 years attending Gynaecological outpatient department of our hospital over a period of one year.Results: Pap smear results were recorded as per Bethesda system. 35% of smears had epithelial cell abnormality with 62.82% normal smear and 2.13%infections, bacterial vaginosis (1.94%) being most common. The highest epithelial cell abnormality was Low grade squamous intraepithelial lesions (29.90%) followed by Atypical squamous cell of undetermined significance (3.2%). High grade squamous intraepithelial lesions and carcinoma were next to follow (0.97% each). 80% of cancers were Squamous cell carcinoma.Conclusion: Premalignant and malignant lesions were found to be common in cervix. Pap test is simple, quick and effective way of screening them. Screening should be done at least once for all woman after the age of 30 as benefit is maximum in this age group.


2018 ◽  
Vol 69 (8) ◽  
pp. 2245-2250
Author(s):  
Costin Berceanu ◽  
Stefan Paitici ◽  
Sabina Berceanu ◽  
Elvira Bratila ◽  
Anca Maria Ofiteru ◽  
...  

It is widely accepted that HPV infection precedes the occurrence of neoplastic disease in a varying time frame, and HPV testing can detect 30-100% more cervical precancers than conventional cytology and 20-50% more precancers than liquid-based cytology. Low-grade squamous intraepithelial lesions include the categories of mild dysplasia, respectively cervical intraepithelial neoplasia grade 1, and complementary, various descriptors indicating the presence of Human papilloma virus, such as koilocytotic atypia or condilomatous dysplasia. High-grade squamous intraepithelial lesions cytologically consist of moderate and severe dysplasia, respectively cervical intraepithelial neoplasia grade 2, 3 and carcinoma in situ. The purpose of our paper is to analyze the cytological and colposcopic characteristics in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions cervical lesions and to accomplish histological and immunohistochemical correlations in these cervical intraepithelial lesions. Systematic three-step colposcopic evaluation using successively, normal saline with or without green filter, acetic acid and Lugol staining provides enhanced efficiency to the colposcopic examination and allows a more individualized and targeted surgical, medical or expectant management. Special microscopic techniques are very important in diagnosing and grading cervical intraepithelial neoplasia.


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