P16/Ki-67 Immunostaining is Useful in Stratification of Atypical Metaplastic Epithelium of the Cervix

Cervical metaplastic squamous epithelium exhibiting atypia insufficient for a diagnosis of cervical intraepithelial neoplasia (CIN) is usually reported as “atypical squamous metaplasia” (ASM). Stratification impacts treatment since the differential is often between reactive and high grade CIN (CIN II, III). Diagnosis with H&E is associated with low intra/interobserver concurrence. P16/Ki-67 immunostains are helpful to assess cervical biopsies for HPV-associated lesions but staining in metaplastic squamous epithelium has received little attention. This study aims to establish staining characteristics of metaplastic squamous epithelium and determine if p16/Ki-67 is useful in ASM stratification. 80 cervical biopsies containing morphologically normal and dysplastic squamous metaplasia were retrieved to determine the staining characteristics of metaplastic epithelium utilizing p16/Ki-67 immunostains. These included 21 benign squamous metaplasia (BSM) from benign cervices, 15 BSM present adjacent to HPV/CIN lesions, and 44 CIN involving squamous metaplasia. Serial sections with controls were stained for p16 and Ki-67 and in-situ hybridization (ISH) for low-risk (LR) and high-risk (HR) HPV was performed. P16 was recorded as negative, spotty, or band-like. Ki-67 was recorded as positive when present in >50% of lesional nuclei. Results were correlated with H&E diagnosis. 95% of the BSMs, whether from normal cervices or adjacent to HPV/CIN were p16/Ki-67 negative. 81% HG CINs involving squamous metaplasia were p16 band/Ki-67 positive. Low grade CIN (CIN I) involving metaplastic epithelium showed a broad distribution of p16/Ki-67 staining patterns. Based on these criteria, 20 ASM were evaluated. 10% of the ASM cases were p16 band/Ki-67 positive indicating HG CIN. 60% of the ASMs were p16/Ki-67 negative indicating reactive change (all with the exception of one case being HPV negative). The remaining 30% of the ASM cases showed variable positivity for p16 and Ki-67 and could not be stratified into the two categories. Thus p16/Ki-67 staining is helpful in stratification of ASM as reactive or CIN.

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

Journal of Laboratory Physicians ◽

10.4103/0974-2727.199630 ◽

2017 ◽

Vol 9 (02) ◽

pp. 104-110 ◽

Cited By ~ 1

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.

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p16INK4a, Cytokeratin 7, and Ki-67 as Potential Markers for Low-Grade Cervical Intraepithelial Neoplasia Progression

Journal of Lower Genital Tract Disease ◽

10.1097/lgt.0000000000000310 ◽

2017 ◽

Vol 21 (3) ◽

pp. 171-176 ◽

Cited By ~ 2

Author(s):

Larissa Bastos Eloy da Costa ◽

Renata De Marchi Triglia ◽

Liliana A. Lucci De Angelo Andrade

Keyword(s):

Cervical Intraepithelial Neoplasia ◽

Intraepithelial Neoplasia ◽

Low Grade ◽

Cytokeratin 7 ◽

Ki 67

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Ki-67 expression in anal intraepithelial neoplasia in AIDS

Sao Paulo Medical Journal ◽

10.1590/s1516-31802001000300007 ◽

2001 ◽

Vol 119 (3) ◽

pp. 119-121 ◽

Cited By ~ 7

Author(s):

Edenilson Eduardo Calore ◽

Carmen Ruth Manzione ◽

Sidney Roberto Nadal ◽

Maria José Cavalieri ◽

Nilda Maria Perez Calore ◽

...

Keyword(s):

Lower Layer ◽

Intraepithelial Neoplasia ◽

Cell Counting ◽

Biological Behavior ◽

Low Grade ◽

High Grade ◽

Ki 67 ◽

Staining Techniques ◽

The Mean ◽

Group 2

CONTEXT: AIDS is one of the most important risk factors for progression and recurrence of anogenital condyloma. In a previous work, we observed that patients with warts and high-grade AIN (HAIN) had recurrences more frequently than did patients with warts without AIN. The mechanisms of this increased incidence of high-grade lesions in AIDS are not known. OBJECTIVE: We studied the expression of the proliferative marker Ki-67 by immunohistochemical methods, in specimens of anal condyloma from HIV+ patients to clarify whether its expression can be associated to the grade of AIN. DESIGN: A retrospective study of hiltological specimens. SETTING: University referral unit. SAMPLE: 34 patients were divided into two groups: (1) condylomas with low grade AIN (LAIN), with 25 patients; and (2) condylomas with HAIN, with 9 patients. In this latter group we examined two areas: 2A (HAIN area) and 2B (LAIN area). MAIN MEASUREMENTS: The immunohistochemical reaction for Ki-67 was done on histological sections. Slices were lightly stained with hematoxylin, to help us in Ki-67 positive cell counting. The percentage of Ki-67 marked nuclei was calculated. We applied one-way variance analysis for statistics. RESULTS: The mean number of Ki-67 positive cells in group 1 was 19.68 ± 10.99; in group 2 (area A) it was 46.73 ± 10.409; and in area B it was 36.43 ± 14.731. There were statistical differences between groups 1 and 2A and between groups 1 and 2B. Ki-67 positive cells predominated in the lower layer in LAIN. Positive Ki-67 cells were found in all layers in group 2A, and in group 2B they predominated in the two lower or in all layers of the epithelium. CONCLUSIONS: Our results suggest that LAIN areas (using routine staining techniques) in HAIN can have a biological behavior more similar to HAIN.

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HER2 Status in Premalignant, Early, and Advanced Neoplastic Lesions of the Stomach

Disease Markers ◽

10.1155/2015/234851 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 16

Author(s):

A. Ieni ◽

V. Barresi ◽

L. Rigoli ◽

R. A. Caruso ◽

G. Tuccari

Keyword(s):

Current Knowledge ◽

Intraepithelial Neoplasia ◽

Disease Recurrence ◽

Her2 Status ◽

Her2 Overexpression ◽

Low Grade ◽

High Grade ◽

Gastric Lesions ◽

Ki 67 ◽

Gastric Type

Objectives. HER2 expression in gastric cancer (GC) has received attention as a potential target for therapy with Trastuzumab. We reviewed the current knowledge on HER2 status in premalignant gastric lesions and in early (EGC) and advanced (AGC) GC to discuss the possible pathogenetic and prognostic roles of HER2 overexpression in GC.Results. HER2 overexpression was documented in gastric low-grade (LG) and high-grade intraepithelial neoplasia (HG-IEN), with higher frequency in gastric type dysplasia. HER2 overexpression was significantly associated with disease recurrence and poor prognosis in EGC representing an independent risk factor for lymph node metastases. HER2 overexpression was more frequent in AGC characterized by high grade, advanced stage, and high Ki-67 labeling index. The discordance in HER2 status was evidenced between primitive GC and synchronous or metachronous metastases.Conclusions. HER2 overexpression in premalignant gastric lesions suggests its potential involvement in the early steps of gastric carcinogenesis. The assessment of HER2 status in EGC may be helpful for the identification of patients who are at low risk for developing nodal metastases. Finally, the possible discordance in HER2 status between primary GC and its synchronous metastases support routine assessment of HER2 both in the primary GC and in its metastatic lesions.

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Computer-assisted quantitative analysis of Ki-67 antigen in dysplasia: Associated lesions or masses in ulcerative colitis

Vojnosanitetski pregled ◽

10.2298/vsp0711753z ◽

2007 ◽

Vol 64 (11) ◽

pp. 753-758

Author(s):

Vesna Zivkovic ◽

Aleksandar Petrovic ◽

Biljana Djordjevic ◽

Vuka Katic ◽

Jasmina Gligorijevic ◽

...

Keyword(s):

Immunohistochemical Staining ◽

Staining Intensity ◽

High Grade Dysplasia ◽

Computer Assisted ◽

Low Grade ◽

High Grade ◽

Ki 67 ◽

Associated Lesions ◽

Low Grade Dysplasia ◽

The Difference

Background/Aim. The aim of this study was to apply computer- assisted methodology in assessment of Ki-67 positivity in "adenoma-like" dysplasia associated lesions or masses (DALMs), and carcinoma in ulcerative colitis (UC), and to determine a new approach to grading of Ki-67 staining intensity. Methods. Immunohistochemical slides were quantitatively analyzed for estimation of proportion and intensity of Ki-67 positive-stained cells in a total of 50 "adenoma-like" DALMs (27 with low-grade dysplasia and 23 with high-grade dysplasia), and 17 adenocarcinomas associated with UC. The four grades of immunohistochemical staining intensity were established by an automated classification of nuclear optical densities. Results. The Ki-67 labeling index (LI) in low-grade dysplasia was significantly lower than in high-grade dysplasia, and carcinoma (p < 0.001). The Ki-67 LI of carcinomas was not significantly different from the value obtained in highgrade dysplasia (p > 0.05), however having the difference in percentage values of the moderate stained nuclei (p < 0.05). The overall average values of chromogene nuclear optical density, showed statistically significant differences between DALMs and carcinoma (p < 0.05), although not between normal mucosa and low-grade dysplasia (p > 0.05). Conclusion. The obtained results imply, according to the overall percentage of labeled nuclei, that high-grade dysplasia is very close to carcinoma, while there is the difference in the percentage of moderately stained nuclei. We showed that Ki-67 positivity have a different internal distribution which could be useful in analysing these lesions. These findings also, indicate the important biological differences between low-grade dysplasia and carcinoma in UC, and a low proliferative potential of the former. Automated image analysis permits an objective estimation of Ki-67 immunohistochemical staining in UCassociated dysplasia and carcinoma.

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

10.1055/s-0039-1685267 ◽

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.

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Diagnostic Implications of L1, p16, and Ki-67 Proteins and HPV DNA in Low-grade Cervical Intraepithelial Neoplasia

International Journal of Gynecological Pathology ◽

10.1097/pgp.0b013e31821ac4fd ◽

2011 ◽

Vol 30 (6) ◽

pp. 597-604 ◽

Cited By ~ 8

Author(s):

Luisa Benerini Gatta ◽

Angiola Berenzi ◽

Piera Balzarini ◽

Enrico Dessy ◽

Francesca Angiero ◽

...

Keyword(s):

Cervical Intraepithelial Neoplasia ◽

Intraepithelial Neoplasia ◽

Low Grade ◽

Ki 67 ◽

Hpv Dna

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Thyroid-Like Low-Grade Nasopharyngeal Papillary Adenocarcinoma

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz082 ◽

2019 ◽

Vol 152 (5) ◽

pp. 582-589 ◽

Cited By ~ 1

Author(s):

Fengbo Huang ◽

Xueping Xiang ◽

Bo Hong ◽

Jie Min ◽

Jinfan Li

Keyword(s):

Hot Spot ◽

Gene Mutations ◽

Papillary Adenocarcinoma ◽

Morphological Characterization ◽

Low Grade ◽

Ki 67 ◽

Appropriate Treatment ◽

Rule Out

Abstract Objectives Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TLLGNPPA) is a relatively rare nasopharyngeal tumor. We performed morphological characterization, immunohistochemical profiling, and investigated gene mutations. We also provide clinical follow-up data and brief review of the literature. Methods Immunohistochemistry was used to evaluate the expression of TTF-1, CK19, CK7, EMA, TG, Pax-8, CK5/6, S100, and Ki-67. Additionally, in situ hybridization was utilized to identify the presence of EBV. We investigated mutations in hot-spot exons of KRAS/NRAS/BRAF to rule out common mutations seen in thyroid tumors. Results Histopathologic examination of four cases identified tumors that were mainly occupied by papillary architectures. One case had a predominantly glandular structure. The tumors expressed TTF-1 and CK19, while TG and Pax-8 were negative. S100 was moderately expressed focally in three cases. Conclusions While TLLGNPPA displays a morphological resemblance to papillary thyroid carcinoma (PTC), it is vital to differentiate nasopharyngeal metastasis from PTC for appropriate treatment.

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Characteristics and potential malignancy of colorectal juvenile polyps in adults: a single-center retrospective study in China

10.21203/rs.3.rs-362901/v1 ◽

2021 ◽

Author(s):

Jie Dong ◽

Tian-Shi Ma ◽

Yuan-Hong Xu ◽

Peng Li ◽

Wan-Yuan Chen ◽

...

Keyword(s):

Sigmoid Colon ◽

Intraepithelial Neoplasia ◽

Diagnostic Value ◽

Juvenile Polyp ◽

Low Grade ◽

Ki 67 ◽

Juvenile Polyps ◽

Chicken Skin ◽

Well Differentiated ◽

Skin Mucosa

Abstract BackgroundColorectal juvenile polyps are rare and usually considered benign in adults. Carcinogenesis or neoplastic changes are rarely mentioned in the literature. We aimed to systematically evaluate the characteristics and potential malignancy of colorectal juvenile polyps in adults.MethodsWe retrospectively reviewed the medical records of 103 adults diagnosed with colorectal juvenile polyps from 9/2007 to 5/2020 in our hospital. The characteristics, endoscopic findings, occurrence of intraepithelial neoplasia, carcinogenesis and diagnostic value of chicken skin mucosa (CSM) were analyzed.ResultsThe average age of patients with juvenile polyps was 43.2 years (range, 19 to 78). A total of 101 patients (101/103, 98.1%) had a single juvenile polyp, while two had multiple polyps (107 polyps in total). Polyp sizes ranged from 0.5 to 5 cm. One (1/107, 0.9%) juvenile polyp was cancerous, and 7 (7/107, 6.5%) developed low-grade intraepithelial neoplasia. Neoplasia or cancerization was not associated with the number of polyps. A 27-year-old female had a polyp with well-differentiated adenocarcinoma in the mucosa that was 2 cm in the sigmoid colon with erosion on the surface. According to immunohistochemistry, the Ki-67 was approximately 80%. P53 was mutated with diffuse and strongly positive expression. CSM was observed beside 17 polyps, which were all located in the rectum and sigmoid colon; one polyp had low-grade intraepithelial neoplasia.ConclusionsColorectal juvenile polyps in adults have neoplastic potential. Neither neoplasia nor carcinogenesis was associated with the number of polyps. CSM was not a tumorigenesis marker in colorectal juvenile polyps in the distant colorectum. Colorectal juvenile polyps in adult may go through a ‘low-grade intraepithelial neoplasia to high-grade intraepithelial neoplasia to carcinoma’ path and should be treated and regularly followed up as adenomas.

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