Association of p16 and Ki-67 with Risk of Recurrence in Previously Treated Cervical High-Grade Squamous Intraepithelial Lesions

2021 ◽  
pp. 1-6
Author(s):  
Carlos Germán Arredondo-Gálvez ◽  
Denise Acuña-González ◽  
David Cantú-de-León ◽  
José Gregorio Chanona-Vilchis ◽  
Alejandro Avilés-Salas ◽  
...  
Keyword(s):  
Immunohistochemical Analysis ◽  
Time Frame ◽  
Control Group ◽  
High Grade ◽  
Ki 67 ◽  
Exact Test ◽  
Risk Of Recurrence ◽  
Logistic Regression Models ◽  
Previously Treated ◽  
P16 Expression

<b><i>Objective:</i></b> Our main objective was to assess the association between the markers p16 and Ki-67 and recurrence of disease in patients previously treated for cervical high-grade squamous intraepithelial lesion (HSIL). <b><i>Design:</i></b> This is a case-control study at the National Cancer Institute conducted between 2005 and 2015. Of the patients with a pathologically confirmed diagnosis of HSIL, 107 cases were selected. They were divided into 2 groups: 28 cases with recurrence after treatment and a control group of 79 patients without recurrence. We identified clinical, pathological, and treatment variables. <b><i>Methods:</i></b> Two experienced pathologists performed immunohistochemical analysis of biomarkers; they agreed on their interpretation, and we calculated the odds ratios (ORs) associated with recurrence. For group comparisons, we used the Wilcoxon signed-rank, χ<sup>2</sup>, or Fisher’s exact test, depending on the type of variable. We conducted logistic regression models to estimate ORs and determine the factors associated with recurrence. The recurrence-free period was defined as the time frame between conization and either recurrence of disease or the last date the patient was seen. We used Kaplan-Meier plots to visualize survival curves and log-rank tests to compare the curves. We established a <i>p</i> value &#x3c;0.05 as statistically significant. <b><i>Results:</i></b> After pathologists performed immunohistochemical analysis, they achieved an agreement level of 83.7% for p16 and 60% for Ki-67. We did not find an association between recurrence and either p16 expression (<i>p</i> = 0.69) or the percentage of Ki-67 expression (<i>p</i> = 0.71). The recurrence-free period analysis did not reveal a difference in p16 expression (<i>p</i> = 0.57) nor in the percentage of Ki-67 expression in the 3-tiered scale (<i>p</i> = 0.56). <b><i>Limitations:</i></b> Our main limitation was a reduced sample size. <b><i>Conclusion:</i></b> We found no association between p16 and Ki-67 positivity and the risk of recurrence in previously treated HSIL.

Experience of using the drug Glutoxim in patients with benign and borderline epithelial ovarian tumors after performing conservative surgical treatment

2018 ◽  
pp. 79-86
Author(s):  
A.A. Sukhanova ◽  
◽  
M.Yu. Yegorov ◽  
Keyword(s):  
Surgical Treatment ◽  
High Risk ◽  
Ovarian Tumors ◽  
Molecular Profile ◽  
Control Group ◽  
Profile Data ◽  
Ki 67 ◽  
Risk Of Recurrence ◽  
Relapse Therapy ◽  
E Cadherin

The objective: to increase the effectiveness of treatment of patients with benign and borderline epithelial ovarian tumors (EOT) after conservative operations performed based on the definition of a high risk group for recurrence and malignancy according to the molecular expression profile of the markers p53, Ki-67, estrogen receptors (ER), CD34 and E-cadherin and inclusion in the complex anti-relapse therapy of the immunomodulating drug Glutoxim. Materials and methods. A clinical examination of 60 patients of reproductive age with EOT was performed, which were treated with organ-sparing surgical treatment (main group). Of these 60 patients, 30 women (subgroup I) were diagnosed with benign EOT (BEOT), the remaining 30 women (subgroup II) were diagnosed with borderline EOT (BoEOT) Ia and Ib stages in FIGO. In removed tumors after routine histopathological examination, the molecular profile was determined by immunohistochemically determining the protein regulator of apoptosis p53, proliferation index (PI) by Ki-67 expression, estrogen receptors — ER, microvessel density by CD34 expression and E-cadherin intercellular adhesion protein. Based on the molecular profile determination data, the removed tumor was ranked as high or low risk of recurrence and malignancy. Patients from the high-risk group for relapse and malignancy according to the molecular profile data included the immunomodulating drug Glutoxim in the complex anti-relapse therapy - intramuscularly 10 mg daily for 2 weeks with a course repeated every six months for 3 years. The control group consisted of 64 patients with BEOT and BoEOT, who underwent conservative surgical treatment without further anti-relapse treatment. Results. During the molecular profile study, it was found that high risk of recurrence and malignancy had EOT with p53 expression (LI ≥15%), high proliferative activity of cells with Ki-67 expression (PI ≥10%), low estrogen reception (LI ER < 49.5%), high density of microvessels on the expression of CD34 (IM ≥40 mv /mm2), low level of intercellular adhesion on the expression of E-cadherin (LI <59%). Molecular profile characterizing a high risk of recurrence and malignancy, in most cases was inherent in BoEOT. The purpose of a comprehensive anti-relapse treatment with the inclusion of the immunomodulatory drug Glutoxim (intramuscularly daily at 10 mg for 2 weeks) after performing of sparing conservative surgical treatment with a repetition of the course every six months in patients at high risk of relapse and malignancy according to molecular profile data has reduced the relapse of EOT to 6.7% in patients of the main group compared with 20.3% in the control group during three years of follow-up observation of patients. The difference is statistically significant (p <0.05). Conclusion. In order to prevent cases of recurrence and malignancy in patients with EOT at high risk of relapse and malignancy according to molecular profile data after a sparing surgical treatment that preserves their reproductive function, it is recommended that Glutoxim is administered in complex anti-relapse therapy at 10 mg intramuscularly per every day for 2 weeks with a repetition of the course every six months for 3 years. Key words: benign epithelial ovarian tumors, borderline epithelial ovarian tumors, high risks of recurrence and malignancy, anti-relapse therapy, reproductive function, Glutoxim.

scholarly journals Clear Cell Carcinomas of the Mullerian System: Does the Pathogenesis Vary Depending on Their Nuclear Grade and Their Association with Endometriosis? An Immunohistochemical Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmad Alduaij ◽  
Katrine Hansen ◽  
Tahreem A. Karim ◽  
Cunxian Zhang ◽  
Michelle M. Lomme ◽  
...  
Keyword(s):  
Clear Cell ◽  
Immunohistochemical Analysis ◽  
Nuclear Grade ◽  
High Grade ◽  
Ki 67 ◽  
High Nuclear Grade ◽  
Positive Immunostaining

Clear cell carcinomas (CCC) of the mullerian system are considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis. Conclusions: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings.

scholarly journals Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Brigita Glebauskiene ◽  
Rasa Liutkeviciene ◽  
Alvita Vilkeviciute ◽  
Inga Gudinaviciene ◽  
Aurelija Rocyte ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Immunohistochemical Analysis ◽  
Serum Levels ◽  
Labelling Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
Median Serum

The aim of the present study was to determine if the Ki-67 labelling index reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration in blood serum of pituitary adenoma patients. The study was conducted in the Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were analysed based on magnetic resonance imaging findings. The suprasellar extension and sphenoid sinus invasion by pituitary adenoma were classified according to Hardy classification modified by Wilson. Knosp classification system was used to quantify the invasion of the cavernous sinus. The Ki-67 labelling index was obtained by immunohistochemical analysis with the monoclonal antibody, and serum levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Sixty-nine PA tissue samples were investigated. Serum levels of IL–17A were determined in 60 patients with PA and 64 control subjects. Analysis revealed statistically significantly higher Ki-67 labelling index in invasive compared to noninvasive pituitary adenomas. Median serum IL-17A level was higher in the pituitary adenoma patients than in the control group. Conclusion. IL-17A might be a significant marker for patients with pituitary adenoma and Ki-67 labelling index in case of invasive pituitary adenomas.

scholarly journals Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Aneta Popiel ◽  
Aleksandra Piotrowska ◽  
Patrycja Sputa-Grzegrzolka ◽  
Beata Smolarz ◽  
Hanna Romanowicz ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Precancerous Lesions ◽  
Clinical Stage ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Control Group ◽  
Ki 67 ◽  
Cervical Precancerous Lesions ◽  
P16 Expression

Cervical cancer is one of the most common malignant cancers in women worldwide. The 5-year survival rate is 65%; nevertheless, it depends on race, age, and clinical stage. In the oncogenesis of cervical cancer, persistent HPV infection plays a pivotal role. It disrupts the expression of key proteins as Ki-67, p16, involved in regulating the cell cycle. This study aimed to identify the potential role of testin in the diagnosis of cervical precancerous lesions (CIN). The study was performed on selected archival paraffin-embedded specimens of CIN1 (31), CIN2 (75), and CIN3 (123). Moderate positive correlation was observed between testin and Ki-67 as well as testin and p16 expression in all dysplastic lesions (r = 0.4209, r = 0.5681; p < 0.0001 for both). Statistical analysis showed stronger expression of the testin in dysplastic lesions vs. control group (p < 0.0001); moreover, expression was significantly higher in HSIL than LSIL group (p < 0.0024). In addition, a significantly stronger expression of testin was observed in CIN3 vs. CIN1 and CIN3 vs. CIN2. In our study, expression of Ki-67, p16, and testin increased gradually as the lesion progressed from LSIL to HSIL. The three markers complemented each other effectively, which may improve test sensitivity and specificity when used jointly.

Proposal of a Panel of Genes Identified by miRNA Profiling as Candidate Prognostic Biomarkers in Lung Carcinoids

2020 ◽  
Vol 111 (1-2) ◽  
pp. 115-122
Author(s):  
Ida Rapa ◽  
Arianna Votta ◽  
Jessica Giorcelli ◽  
Stefania Izzo ◽  
Angelica Rigutto ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
In Silico Analysis ◽  
Tumor Grade ◽  
Control Group ◽  
High Grade ◽  
Ki 67 ◽  
Free Survival ◽  
Element Binding Protein ◽  
Positive Nodal Status ◽  
Disease Free

<b><i>Aim:</i></b> To validate the prognostic role of a panel of genes previously uncovered by our group to be specific targets of miRNAs differentially expressed in lung carcinoids with aggressive pathological features. <b><i>Methods:</i></b> Four genes, namely, cyclic AMP response element binding protein-1 (<i>CREBP1</i>), activin A receptor type 2B (<i>ACVR2B</i>), LIM homeobox 2 (<i>LHX2</i>), and Krüppel-like factor 12 (<i>KLF12</i>), were identified in a previous study by our group using in silico analysis to be regulated by 3 miRNAs (miR-409-3p, miR-409-5p, and miR-431-5p) that were shown to be downregulated in aggressive lung carcinoids. These genes were analyzed using real-time PCR in a cohort of 102 lung carcinoids. Fifty high-grade lung carcinomas served as control group. Their expression was correlated with the expression of miR-409-3p, miR-409-5p, and miR-431-5p and with clinical pathological parameters and disease-free survival. <b><i>Results:</i></b> The expression of all but <i>CREBP1</i> gene was significantly different between lung carcinoids and high-grade neuroendocrine carcinomas. <i>ACVR2B</i> and <i>LHX2</i> were significantly inversely correlated with miR-409-3p and miR-409-5p. High levels of <i>ACVR2B</i> and <i>LHX2</i> were significantly associated with atypical histotype, high tumor grade, and higher proliferation Ki-67 index (all <i>p</i> &#x3c; 0.05). Low levels of <i>KLF12</i> were significantly associated with the presence of necrosis and positive nodal status (all <i>p</i> &#x3c; 0.05). Finally, low <i>KLF12</i> expression was associated with shorter disease-free survival in lung carcinoids as a whole and in atypical carcinoids, only (all <i>p</i> &#x3c; 0.001). <b><i>Conclusions:</i></b> <i>ACVR2B</i>, <i>LHX2</i>, and <i>KFL12</i> are novel potential biomarkers associated with aggressive features in lung carcinoids.

scholarly journals Evaluation of the p16 and Ki-67 Biomarkers as Predictors of the Recurrence of Premalignant Cervical Cancer Lesions after LEEP Conization

2017 ◽  
Vol 39 (06) ◽  
pp. 288-293
Author(s):  
Paulo Leite ◽  
Luciene Tafuri ◽  
Maria Costa ◽  
Maria Lima ◽  
Renata Simões
Keyword(s):  
Immunohistochemical Analysis ◽  
Control Group ◽  
Low Grade ◽  
Cervical Lesions ◽  
Retrospective Case ◽  
Ki 67 ◽  
The Social ◽  
Total Analysis ◽  
Control Study ◽  
Loop Electrosurgical Excision

Objective To evaluate the expressions of biomarkers p16 and Ki-67 in low-grade (LG) or high-grade (HG) lesions, and to relate them to risk factors and the recurrence of these lesions. Methods A retrospective case-control study of 86 patients with LG and HG lesions who underwent a loop electrosurgical excision procedure (LEEP) between 1999 and 2004. The control group was composed of 69 women with no recurrence, and the study group, of 17 patients with recurrence. All patients were followed-up over a two-year period after surgery, and screened every six months, including cytology and colposcopy. Biopsy samples collected from LEEP were submitted to immunohistochemical analysis for p16 and Ki-67. The statistical analysis was performed using the Statistical Package for the Social Sciences software (SPSS, IBM-SPSS, Inc., Chicago, IL, US), with a significant p ​​< 0.05. Results The biomarkers p16 and Ki-67, separately or combined, showed no relation to recurrence on the total analysis. However, evaluating specifically HG lesions, the positive expression (2+ and 3+) of p16/Ki-67 was associated with recurrence (0.010). In addition, p16 isolated was also more expressive in HG lesions (2+ and 3 + , p = 0.018), but it was unrelated to recurrence. Conclusion Proteins p16 and Ki-67, both isolated and combined, are not reliable primary markers for the recurrence of cervical lesions in the majority of LG lesions. However, analyzing only the group with prior diagnosis of HG lesions, the expressions of p16 and of p16/Ki-67 were associated with recurrence, and they may be useful in monitoring these cases.

Venous Thromboembolism and High Grade Gliomas

1993 ◽  
Vol 70 (03) ◽  
pp. 393-396 ◽  
Author(s):  
Mandeep S Dhami ◽  
Robert D Bona ◽  
John A Calogero ◽  
Richard M Hellman
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Medical Center ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Fisher Exact Test ◽  
High Grade ◽  
Chi Square ◽  
Exact Test ◽  
High Grade Gliomas

SummaryA retrospective study was done to determine the incidence of and the risk factors predisposing to clinical venous thromboembolism (VTE) in patients treated for high grade gliomas. Medical records of 68 consecutive patients diagnosed and treated at Saint Francis Hospital and Medical Center from January 1986 to June 1991 were reviewed. The follow up was to time of death or at least 6 months (up to December 1991). All clinically suspected episodes of VTE were confirmed by objective tests. Sixteen episodes of VTE were detected in 13 patients for an overall episode rate of 23.5%. Administration of chemotherapy (p = 0.027, two tailed Fisher exact test) and presence of paresis (p = 0.031, two tailed Fisher exact test) were statistically significant risk factors for the development of VTE. Thrombotic events were more likely to occur in the paretic limb and this difference was statistically significant (p = 0.00049, chi square test, with Yates correction). No major bleeding complications were seen in the nine episodes treated with long term anticoagulation.We conclude that venous thromboembolic complications are frequently encountered in patients being treated for high grade gliomas and the presence of paresis and the administration of chemotherapy increases the risk of such complications.

Success Rate of Obturation of Root Canals by Different Techniques in Primary Molars: A Comparative Clinical Study

2020 ◽  
Vol 2 (1) ◽  
pp. 36-44
Author(s):  
Satyawan G. Damle ◽  
Ritika Bansal ◽  
Dhanashree D. Sakhare
Keyword(s):  
Success Rate ◽  
Study Groups ◽  
Primary Molars ◽  
Control Group ◽  
Second Primary ◽  
Chi Square ◽  
Exact Test ◽  
Root Canals ◽  
Significant Difference ◽  
Comparative Clinical Study

Objective: To compare the success rate of different obturation procedures in primary mandibular second molars clinically and also by digital radiovisiography. Methods: A total of 40 children aged between 4-8 years with deeply carious mandibular second primary molars indicated for single session pulpectomy were selected. Canals were obturated with Metapex. The 3 study groups (Endodontic plugger, Handheld lentulospiral, Navi Tip syringe) were compared with the control group (reamer) both clinically and radiovisiographically. The data collected were statistically analyzed using Pearson’s Chi-square and Fisher’s exact test. Results: The use of Navi tip syringe led to the least number of voids followed by Endodontic plugger and Reamer and the highest number of voids was reported with Lentulospiral. Navitip presented maximum number of optimally filled cases followed by Endodontic plugger and Lentulospiral and least number of optimally filled cases with reamer. However, there was no statistically significant difference (p>0.05) in any of the groups with clinical (pain and tenderness to percussion) and radiographic parameters (presence or absence of voids and length of obturation). Conclusion: Within the limitations of the present study, though the clinical outcome was statistically insignificant, Navitip syringe exhibited encouraging results and is a promising option for obturation in primary teeth.

scholarly journals Relationship between Expanded Disability Status Scale scores and the presence of temporomandibular disorders in patients with multiple sclerosis

2018 ◽  
Vol 12 (01) ◽  
pp. 144-148 ◽  
Author(s):  
Lucas Senra Correa Carvalho ◽  
Osvaldo José Moreira Nascimento ◽  
Luciane Lacerda Franco Rocha Rodrigues ◽  
Andre Palma Da Cunha Matta
Keyword(s):  
Multiple Sclerosis ◽  
Temporomandibular Disorders ◽  
Control Group ◽  
Expanded Disability Status Scale ◽  
Exact Test ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Scale Scores ◽  
Axis I ◽  
Relapsing Remitting Multiple Sclerosis

ABSTRACTObjectives: The objectives of this study were to assess the prevalence of temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple sclerosis (MS) and to investigate whether an association exists between the presence of TMD symptoms and the degree of MS-related disability. Materials and Methods: In all, 120 individuals were evaluated: 60 patients with a diagnosis of relapsing-remitting MS and 60 age- and sex-matched controls without neurological impairments. A questionnaire recommended by the European Academy of Craniomandibular Disorders for the assessment of TMD symptoms was administered. For those who answered affirmatively to at least one of the questions, the RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes. The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS-related disability. Statistical Analysis Used: Fisher’s exact test was used to analyze the data. ANOVA was used to detect significant differences between means and to assess whether the factors influenced any of the dependent variables by comparing means from the different groups. Results: The prevalence of TMD symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P = 0.0001). There were statistically significant differences between degrees of MS-related disability and the prevalence of TMD (P = 0.0288). Conclusions: The prevalence of both TMD and TMD symptoms was significantly greater in the MS group. EDSS scores and TMD prevalence rates were inversely related.

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