Survivin as a Useful Adjunct Marker for the Grading of Papillary Urothelial Carcinoma

2008 ◽  
Vol 132 (2) ◽  
pp. 224-231
Author(s):  
Ying-bei Chen ◽  
Jiangling J. Tu ◽  
Jean Kao ◽  
Xi K. Zhou ◽  
Yao-Tseng Chen
Keyword(s):  
Urothelial Carcinoma ◽  
Messenger Rna ◽  
Interobserver Variability ◽  
World Health ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Grade Group ◽  
Ki 67 ◽  
Papillary Urothelial Carcinoma

Abstract Context.—Distinguishing low-grade and high-grade noninvasive papillary urothelial carcinoma based on morphologic criteria can be challenging and adjunct markers are highly desirable. Survivin, presumably an antiapoptotic protein, was previously proposed as a prognostic marker for urothelial carcinoma. Objective.—To assess interobserver variability by 2004 World Health Organization classification and the value of survivin and Ki-67 as potential markers for grading noninvasive papillary urothelial carcinoma. Design.—Fifty-one bladder biopsies were graded blindly by 5 experienced general surgical pathologists. The protein and messenger RNA expression of survivin and Ki-67 was evaluated by immunohistochemistry and quantitative reverse transcription–polymerase chain reaction using paraffin-embedded tissue. The immunohistochemistry result was quantitatively analyzed using a computer-based color deconvolution module. Results.—The diagnostic agreement among 5 pathologists was fair to poor, with 32% of the cases graded differently by at least 2 raters. All cases were divided into 3 groups: consensus low-grade, consensus high-grade, and indeterminate. The percentage of urothelial cells with positive survivin nuclear staining (survivin score) was significantly higher in the high-grade than in the low-grade group (P < .001). Survivin score outperformed Ki-67 in separating the high-grade group from the low-grade group and showed a significantly higher predictive accuracy for high-grade recurrence than the histologic grade. The disagreement of grading for the indeterminate group could be resolved by their survivin scores in most cases. Survivin messenger RNA level correlated well with survivin score by immunohistochemistry but was not a more discriminating marker. Conclusions—Significant interobserver variability exists in grading low-grade versus high-grade papillary urothelial carcinoma. Survivin immunohistochemical staining can be a useful adjunct tool for the grading of challenging cases.

Umbrella Cells Mimicking Focal High-Grade Urothelial Carcinoma in Low-Grade Papillary Urothelial Carcinoma

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S121-S121
Author(s):  
Muhammad Masood Hassan ◽  
Tammey Naab ◽  
Ali Afsari
Keyword(s):  
Urothelial Carcinoma ◽  
Proliferation Index ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Prostate Hyperplasia ◽  
History Of ◽  
Papillary Urothelial Carcinoma ◽  
Artery Disease ◽  
Umbrella Cells

Abstract Objectives Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment. Methods A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC. Results Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells. Conclusion Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.

Comparative Evaluation of ProEx C and ImmunoCyt/uCyt Assays in Atypical Urine Cytology

2014 ◽  
Vol 138 (9) ◽  
pp. 1215-1222 ◽  
Author(s):  
Maria E. Vergara-Lluri ◽  
Eugenia Hu ◽  
Jian-Yu Rao ◽  
Mary Levin ◽  
Sophia K. Apple ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Topoisomerase Ii ◽  
High Sensitivity ◽  
Urine Cytology ◽  
Urothelial Cell ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Surgical Biopsy ◽  
Papillary Urothelial Carcinoma

Context.—Detection of urothelial carcinoma by urine cytology can be challenging. Recently, ProEx C has been studied as a marker to improve detection of urothelial carcinoma. ProEx C is an assay targeting expression of topoisomerase II-α and the minichromosome maintenance protein-2 and is used to assist in diagnoses of gynecologic specimens. Objective.—To evaluate the utility of ProEx C and uCyt in atypical urine cytology. Design.—Sixty-eight specimens with a diagnosis of atypical urine cytology, concurrent uCyt testing, and surgical biopsy follow-up were included. Slides were restained with ProEx C. ProEx C was recorded as positive when nuclear staining was seen in at least one morphologically atypical urothelial cell. The uCyt was scored as positive if at least one morphologically atypical urothelial cell showed positive fluorescence staining. Thirteen cases (19%) had benign histologic diagnoses, 18 (26%) had low-grade papillary urothelial carcinoma, and 37 (54%) had high-grade urothelial carcinoma. Results.—The overall sensitivity was 85% for ProEx C, 85% for uCyt, and 93% for the combination of the 2 assays. The overall specificity was 69% for ProEx C, 31% for uCyt, and 23% for the combination of the 2 tests. In predicting high-grade urothelial carcinoma, sensitivity was 92% for ProEx C, 86% for uCyt, and 92% for both tests. In predicting low-grade papillary urothelial carcinoma, sensitivity was best with the combination of the 2 tests at 94%. Conclusion.—ProEx C has superior specificity to uCyt. The combination of the 2 tests yielded high sensitivity not only for high-grade urothelial carcinoma but also for low-grade papillary urothelial carcinoma.

Low-Grade Papillary Urothelial Carcinoma of the Urinary Bladder: A Clinicopathologic Analysis of a Post–World Health Organization/International Society of Urological Pathology Classification Cohort From a Single Academic Center

2010 ◽  
Vol 134 (8) ◽  
pp. 1160-1163
Author(s):  
Hiroshi Miyamoto ◽  
Fadi Brimo ◽  
Luciana Schultz ◽  
Huihui Ye ◽  
Jeremy S. Miller ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
World Health Organization ◽  
International Society ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
The Mean ◽  
Papillary Urothelial Carcinoma ◽  
Health Organization ◽  
Grade Progression

Abstract Context.—Few large cohort studies have addressed outcome in patients with noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following implementation of the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification. Objective.—To evaluate our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess outcome and interobserver agreement. Design.—Files were searched for all patients diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for accuracy of classification. Results.—A total of 112 cases initially diagnosed as LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by nonurologic pathologists were reclassified as high-grade papillary urothelial carcinoma and were excluded. The mean length of follow-up was 40.1 months (range, 2–113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%), including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high-grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade progression, 7 (37%) also developed stage progression (invasive carcinoma, n  =  5; metastatic carcinoma, n  =  2). Seven patients eventually underwent radical cystectomy. None of the 104 patients died of bladder cancer. The mean number of recurrence episodes was 3.11. The mean durations of time to first recurrence and time to grade progression were 13.9 months and 25.1 months, respectively. The mean size of initial tumors was 1.73 cm. There was no significant correlation between tumor size, patient age, sex, or smoking history and the likelihood for recurrence or grade progression. A significantly higher rate of recurrence was seen in patients with multiple tumors at initial diagnosis (P  =  .04). Conclusions.—A tendency to underdiagnose high-grade papillary urothelial carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa developed recurrence, with an 18.3% incidence of grade progression and a 6.7% incidence of stage progression. Patients with multiple initial tumors had significantly higher risk of developing recurrence.

Correlation of PD-L1 with VEGF and KI-67 index in patients with primary glioma.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 94-94
Author(s):  
Song Xue ◽  
Man Hu ◽  
Jinming Yu ◽  
Bingjie Fan ◽  
Ji Ma
Keyword(s):  
Immune Escape ◽  
Treatment Strategies ◽  
High Grade Glioma ◽  
Continuous Variable ◽  
Low Grade ◽  
High Grade ◽  
Grade Group ◽  
Ki 67 ◽  
Primary Glioma ◽  
The Mean

94 Background: The treatment strategies for glioma, especially glioblastoma multiforme, are not effective. The programmed death ligand 1 (PD-L1) immune escape and increased angiogenesis may be two of the underlying sources of treatment resistance. However, the relationship between these pathways in human glioma is still unknown. Methods: Data for 64 patients with primary glioma recorded from June 2007 to December 2013 in Shan Dong Cancer Hospital were immunohistochemically evaluated for the expressions of PD-L1, VEGF, MMP-9 and KI-67 index. Image ProPlus software was used to quantify the mean optical density (MOD) of the immunohistochemical image. Results: PD-L1 expression was observed in 65.22% of low-grade glioma and 90.24% of high-grade glioma, respectively. The whole expression rate of PD-L1 in glioma was 81.25%. The expression of PD-L1 is significantly related to pathological grade ( p <0.001), VEGF ( p= 0.017) and KI-67 index ( p= 0.009). The mean of PD-L1 MOD in High-grade group was 0.1144±0.02754, higher than that in low-grade group, 0.005129±0.001441 ( p= 0.004). In addition, Expression of VEGF, MMP-9 and KI-67 was significantly different between low-grade and high-grade gliomas ( p= 0.008, 0.04, 0.004 for VEGF, MMP-9 and KI-67, respectively). When analyzed as a continuous variable, the expressions of PD-L1 was positively correlated with VEGF (r = 0.392, p= 0.001) and KI-67 (r = 0.388, p= 0.001). Conclusions: These data suggest, for the first time, that PD-L1 play an important role in glioma angiogenesis and proliferation potential, providing the possibility for considering additional combinations of targeted VEGF therapies and anti-PD-L1 immunotherapy for the treatment of human brain glioma.

scholarly journals HER2 / neu Overexpression in Urothelial Carcinoma and Its Association with Tumour Grading - A Cross Sectional Study from a Tertiary Care Hospital in Kerala

2021 ◽  
Vol 8 (9) ◽  
pp. 497-501
Author(s):  
Sebina Asmi A.T ◽  
Suma Madathiveetil
Keyword(s):  
Urothelial Carcinoma ◽  
Growth Factor Receptor ◽  
Cross Sectional Study ◽  
Low Grade ◽  
High Grade ◽  
Sectional Study ◽  
Tumour Grade ◽  
Cross Sectional ◽  
Epidermal Growth ◽  
Papillary Urothelial Carcinoma

BACKGROUND Human epidermal growth factor receptor-2 HER2 / neu, is a trans membrane tyrosine kinase receptor of epidermal growth factor receptor (EGFR) family and is involved in the pathogenesis of urinary bladder cancer. In this study we attempted to evaluate the HER2 / neu expression in urothelial carcinoma of bladder and its association with tumour grading. METHODS This was a cross sectional study with a sample size of 75. Routine 4 micrometre thick sections of formalin fixed paraffin embedded tissue blocks stained with haematoxylin & eosin were reviewed. Tumour grade was determined by using the World Health Organization (WHO) / International Society of Urological Pathologist criteria (ISUP). Immunohistochemistry was done by using HER2 / neu monoclonal antibody and its expression were observed. The membrane staining intensity and pattern were studied and scored. RESULTS In our study 75 cases of urothelial carcinoma were studied, of which 49 cases were papillary urothelial carcinoma low grade, 26 cases were papillary urothelial carcinoma high grade. Among these, 19 cases were infiltrating urothelial carcinoma. HER2 / neu positivity were observed in 27 (36 %) cases and overexpression in 8 (10 %) cases. Low grade urothelial carcinoma showed HER2 / neu positivity in 11 (22 %) cases and overexpression in 1 (2 %) case. High grade urothelial carcinoma showed HER2 / neu positivity in 16 (64 %) cases, among which 7 (28 %) cases showed overexpression. HER2 / neu positivity was seen in 13 (68 %) cases of infiltrating urothelial carcinoma with 4 (21 %) cases showing overexpression. A statistically significant difference in HER2 / neu expression was noted in high grade and invasive urothelial carcinoma compared to low grade and non-invasive urothelial carcinoma. CONCLUSIONS Urothelial carcinomas show overexpression of HER2 / neu and this over expression increases with increasing grade of tumour and muscle invasiveness. KEYWORDS Urothelial Carcinoma, HER2 / neu, Overexpression, Tumour Grade, Trastuzumab

Correlation of Ki-67 and p53 With the New World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia

2001 ◽  
Vol 125 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Stephen J. Cina ◽  
Kristen J. Lancaster-Weiss ◽  
Kristen Lecksell ◽  
Jonathan I. Epstein
Keyword(s):  
Papillary Carcinoma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Papillary Lesions ◽  
Flat Lesions ◽  
Papillary Hyperplasia ◽  
Health Organization ◽  
Papillary Neoplasm

Abstract Objective.—The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. Design.—We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. Results.—In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. Conclusions.—An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a “field effect” with occult molecular aberration.

Utility of GATA-3 and Cytokeratin 5/6 Immunostains in Separating Condyloma Acuminatum Arising in the Urinary Tract From Non-Invasive Papillary Urothelial Carcinoma

2021 ◽  
pp. 106689692110522
Author(s):  
Diego Montoya-Cerrillo ◽  
Laurence M. Briski ◽  
Merce Jorda ◽  
Oleksandr N. Kryvenko
Keyword(s):  
Urinary Tract ◽  
Urothelial Carcinoma ◽  
Condylomata Acuminata ◽  
Condyloma Acuminatum ◽  
Low Risk ◽  
Low Grade ◽  
High Grade ◽  
Non Invasive ◽  
Urothelial Carcinomas ◽  
Papillary Urothelial Carcinoma

Background Condyloma acuminatum is a squamous epithelial lesion which uncommonly involves the urinary tract. In this location, non-invasive papillary urothelial carcinoma constitutes one of the main differential diagnoses with significant prognostic and therapeutic implications. To date, no ancillary immunohistochemical stain has been described to differentiate these two entities. We assess the utility of cytokeratin 5/6 (CK5/6) and GATA-3 immunohistochemistry in distinguishing condyloma acuminatum from non-invasive papillary urothelial carcinoma. Design We reviewed 9 condylomata acuminata involving the urinary tract, 12 low-grade and 8 high-grade non-invasive papillary urothelial carcinomas. CK5/6 immunostaining was performed in all cases. GATA-3 immunostaining and low-risk human papilloma virus (HPV) chromogenic in situ hybridization was performed in all condyloma cases and 2 urothelial carcinomas with squamous differentiation. Results 8/9 condylomata acuminata were positive for low-risk HPV. All condylomata acuminata exhibited strong full-thickness cytoplasmic staining for CK5/6. In 10 of 12 low-grade non-invasive papillary urothelial carcinomas, CK5/6 expression was continuous and limited to the basal cell layer, while it was patchy and limited to the basal cell layer in all 8 high-grade non-invasive papillary urothelial carcinomas. Two low-grade non-invasive papillary urothelial carcinomas showed focal full-thickness CK5/6 expression in the areas of squamous differentiation. These 2 cases were negative for low-risk HPV. GATA-3 immunostaining was positive in all condylomata acuminata. Conclusions CK5/6 immunostaining is a useful and simple tool that can help separate low-grade and high-grade non-invasive papillary urothelial carcinomas from condyloma acuminatum involving the urothelium-lined organs. GATA-3 has no discriminatory role between condyloma acuminatum and papillary urothelial carcinomas.

scholarly journals Expression of Ki-67 in Low-Grade and High-Grade Astrocytomas

2018 ◽  
Vol 27 (3) ◽  
pp. 225-230
Author(s):  
Cléciton Braga Tavares ◽  
Francisca Das Chagas Sheyla Almeida Gomes Braga ◽  
Emerson Brandão Sousa ◽  
José Nazareno Pearce de Oliveira Brito
Keyword(s):  
Survival Time ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Exclusion Criteria ◽  
World Health Organization Classification ◽  
Ki 67 ◽  
Mesh Terms ◽  
Health Organization ◽  
Selection Of

Objective. This review aims to carry out a survey on the importance of Ki67 in the astrocytomas study. Methods. A search in the electronic database of Medline via PubMed and using MESH terms was carried out. Articles were published between January 2005 and December 2015. All studies were analyzed by two experienced researchers, using inclusion and exclusion criteria for the selection of studies. Results. Five studies showed an association between cell proliferation and survival time. Four articles mentioned as cut-off point for survival a Ki67 of 10% and a fifth article a Ki67 of 14.3. A study showed an association between therapeutic failure and Ki67. Four studies have made the association between Ki67 and World Health Organization classification. Conclusion. High levels of Ki67 are associated to high grade astrocytomas and lower survival time.

scholarly journals HISTOPATHOLOGICAL SPECTRUM OF UROTHELIAL LESIONS: AN OBSERVATIONAL STUDY

2020 ◽  
pp. 1-4
Author(s):  
Nishat Ahmad ◽  
Saurabh Banerjee ◽  
A K. Srivastava
Keyword(s):  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Bladder Tumour ◽  
Histopathological Analysis ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Carcinomas ◽  
Neoplastic Lesions ◽  
Papillary Urothelial Carcinoma ◽  
Muscle Invasion

BACKGROUND: Urinary bladder cancer is second most common cancer after prostate cancer in the genitourinary system. Urothelial Carcinoma is the commonest tumour type accounting for 90% of all primary tumours of the bladder Histopathological analysis of cystoscopic bladder biopsy and Transurethral resection of the bladder tumour (TURBT) material are the mainstay for cancer diagnosis. This study was aimed to determine the frequency of different types of neoplastic lesions of the urinary bladder and to determine the grade and stage of urothelial tumours. MATERIAL METHOD: The study was carried out in the Department of Pathology, Rajendra Institute of Medical Sciences (RIMS), Ranchi from January 2018 to June 2020 and included 30 cases of cystoscopic biopsies and TURBT specimens. RESULTS: Out of 30 cases of neoplastic lesions, majority were of high grade papillary urothelial carcinoma (n=14, 46.67%) followed by low grade papillary urothelial carcinoma (n=9, 30%), 3 cases (10%) were of PUNLMP, 2 cases (6.66%) of papilloma and 1 (3.33%) case each of moderately differentiated squamous cell carcinoma and extra nodal NHL. The most common age group was 41-50 years and 51-60 years with 9 (30%) cases each. Muscle invasion was seen only in high grade papillary urothelial carcinomas. CONCLUSION: High-grade urothelial carcinomas with lamina propria and muscle invasion are the most common neoplastic lesion of urinary bladder with significant morbidity and mortality. Muscle invasion and grading, as per TNM staging, are valuable prognostic factors.

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.

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