scholarly journals Immunohistochemical expression of p16ink4a in inflammatory, preneoplastic and neoplastic cervical lesions

2015 ◽  
Vol 68 (3-4) ◽  
pp. 85-92
Author(s):  
Radoslav Gajanin ◽  
Zivorad Gajanin ◽  
Zoran Vujkovic ◽  
Vesna Gajanin ◽  
Zdenka Gojkovic ◽  
...  

Introduction. High-risk human papilloma viruses play a main role in the development of cervical dysplasias and carcinomas. p16INK4a can be considered as a surrogate marker of active highrisk human papillomaviruses infection in dysplastic and neoplastic cells of the cervix. This study was aimed at determining the presence and level of p16INK4a expression in inflammatory, preneoplastic and neoplastic lesions of the cervix. Material and Methods. The study was performed on 109 samples of cervical biopsy. Cervical cancer was diagnosed in 36 patients, 34 patients had a preneoplastic change (dysplasia) in stratified squamous cervix epithelium and a nonspecific inflammatory process was found in 39 patients. In all samples, immunohistochemical analysis using antibodies to p16INK4a was performed. Results. The expression of p16INK4a was verified in all cases of cervical cancer (100%), in 67.65% of dysplastic cervical lesions and in 38.5% of inflammatory lesions. A statistically highly significant difference was found in the presence and level of expression among neoplasic, dysplastic and inflammatory lesions of the cervix (?? = 76.02, p < 0.001). The expression was more frequent and had a higher level in neoplastic and high grade dysplastic lesions compared to expression in inflammatory lesions and low grade dysplasias. Conclusion. The analysis of the presence of p16INK4a can differentiate non-neoplastic, high grade preneoplastic and neoplastic changes of the cervix. The use of p16INK4a in interpreting borderline lesions of the cervix can enable a rational therapeutic treatment of patients.

2015 ◽  
Vol 143 (1-2) ◽  
pp. 42-49 ◽  
Author(s):  
Zivorad Gajanin ◽  
Rade Vilendecic ◽  
Vesna Ecim-Zlojutro ◽  
Radoslav Gajanin ◽  
Pavle Budakov

Introduction. Most studies point at the main role of humanpapilloma virus (HPV) in the development of dysplasia and cervical cancer. Due to the low specificity and sensitivity of morphological diagnostic methods it is necessary to find an adequate marker which would be introduced in the screening program for cervical cancer. Most research suggests that p16INK4a is a specific and sensitive marker. Objective. The aim of this research was to determine the presence of p16INK4a expression in inflammatory and preneoplastic lesions of the cervix. Methods. The study was performed on 73 samples of cervical biopsy. In 34 patients a preneoplastic change (dysplasia) in the stratified squamous cervix epithelium was found, and in 39 a non-specific inflammatory process was disclosed. In all samples, immunohistochemical analysis using antibodies to p16INK4a was performed. Results. The expression of p16INK4a was verified in 67.65% of cases in dysplastic cervical lesions and 38.5% of the inflammatory lesions. A statistically significant difference was determined in the presence and grade of expression between dysplastic and inflammatory lesions of the cervix (?2=24.16; p<0.001). The expression was more frequent and had a higher grade in dysplastic lesions with high grade and showed a statistically significant difference compared to the expression in low-grade dysplasia (?2=21.48; p<0.001). Conclusion. The analysis of the presence of p16INK4a can differentiate non-neoplastic from preneoplastic changes in the cervix. It is recommended to use immunocytochemical and immunohistochemical analysis using p16INK4a in interpreting borderline lesions of the cervix.


2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Ana Rita Fernandes Miranda da Costa ◽  
Cláudia Sousa ◽  
Erica Isidoro ◽  
Regina Silva ◽  
Cristiana Mourato

Abstract Background Persistent infection by high-risk Human Papillomavirus (hrHPV) are the major cause of cervical cancer. Studies report disparities in the incidence of infection and the various genotypes of this virus in different age groups, suggesting a higher frequency of hrHPV in young women and low-risk subtypes being predominant in older women. This study aimed to investigate the incidence and distribution of hrHPV genotypes in postmenopausal women as well as the correlation with the cytological findings. Methods 16 859 women, aged 50–64 years, performed cervical cancer screening test in Friuri Venezia Giulia region, Italy. The infection was evaluated by the Polymerase Chain Reaction methodology and the positive samples were evaluated by Liquid Based Cytology according to the Bethesda System from 2014. A statistical analysis was performed to study the molecular and cytological data of this population. Results hrHPV infection were found in 5.8% of the women and 78.3% of these were caused by hrHPV other than HPV16 and HPV18 (). Also, 65.7% of the positive samples were negative for intraepithelial lesion or malignancy while low grade squamous intraepithelial lesion was the most frequent (22.4%). There was an increase in the number of high-grade intraepithelial lesions in the presence of HPV16 compared to that recorded when this genotype was absent (20.8% vs. 8.5%). No cervical cancers were detected. Conclusions Infection with hrHPV is uncommon in postmenopausal women and it is mostly caused by subtypes less associated with the development of cervical cancer. Yet, HPV16 infection triggers the development of high-grade lesions.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Malti Kshirsagar ◽  
Wei Jiang ◽  
Ie-Ming Shih

DNA damage commonly occurs in cancer cells as a result of endogenous and tumor microenvironmental stress. In this study, we applied immunohistochemistry to study the expression of phosphorylated Chk2 (pChk2), a surrogate marker of the DNA damage response, in high grade and low grade of ovarian serous carcinoma. A phospho-specific antibody specific for threonine 68 of Chk2 was used for immunohistochemistry on a total of 292 ovarian carcinoma tissues including 250 high-grade and 42 low-grade serous carcinomas. Immunostaining intensity was correlated with clinicopathological features. We found that there was a significant correlation between pChk2 immunostaining intensity and percentage of pChk2 positive cells in tumors and demonstrated that high-grade serous carcinomas expressed an elevated level of pChk2 as compared to low-grade serous carcinomas. Normal ovarian, fallopian tube, ovarian cyst, and serous borderline tumors did not show detectable pChk2 immunoreactivity. There was no significant difference in pChk2 immunoreactivity between primary and recurrent high-grade serous carcinomas. In high-grade serous carcinomas, a significant correlation (P<0.0001) in expression level (both in intensity and percentage) was found between pChk2 and Rsf-1 (HBXAP), a gene involved in chromatin remodeling that is amplified in high-grade serous carcinoma. Our results suggest that the DNA damage response is common in high-grade ovarian serous carcinomas, especially those with Rsf-1 overexpression, suggesting that Rsf-1 may be associated with DNA damage response in high-grade serous carcinomas.


2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 33s-33s
Author(s):  
P. Gyawali ◽  
S.R. KC ◽  
S. Ghimire

Background: Age standardized cervical cancer incidence rate in Nepal is 19.2/100,000 woman, compared with 14.0 worldwide. Similarly, mortality rate is 12.0 women which is significant in comparison with 6.8 worldwide. Cervical intraepithelial neoplasm is a precursor lesion, having high transformation rate into the cervical carcinoma. Data clearly indicates that CIN 2 and 3 has more progression into cervical carcinoma. Despite the fact that Papanicolaou test has remained an important tool in the screening for cervical cancer and has contributed in significant decrease in cervical cancer, sensitivity and specificity of conventional Papanicolaou test is quite low. Colposcopy is visual inspection of cervix under magnification. Study revealed that the positive predictive rate of the colposcopic impression is better as the cervical lesion is more severe. Aim: To find out the significance of colposcopy in the detection of dysplastic cervical lesions and possible use of this method as a screening tool. Methods: This is an observational study done at Cancer Care Foundation, Nepal done from a period of January 2015 to February 2018. Permission was obtained from ethical committee and written consent was obtained from the patients. All the patients suspected having dysplastic or invasive lesions or in whom colposcopy-guided biopsy was performed; were included in the study. Relevant data were collected which included age, colposcopic diagnosis, histopathological diagnosis. Data were entered into Microsoft Excel and statistical analysis was done from statistical package SPSS 21. Results: 6109 females were screened through colposcopy. Out of these 900 patients underwent colposcopy-guided biopsy for being suspected of dysplastic lesions or inflammatory lesions. Mean age of females was 40.65 years. With colposcopy, 407 (45.2%) were suspected to have low grade lesion, followed by 401 (44.6%) high grade lesion and 15 (1.7%) carcinoma. Nonneoplastic lesions were suspected in 77 (8.6%) females. In the histopathological examination low grade dysplasia was observed in 403 (44.8%) followed by 250 (27.8%) high grade dysplasia and 8 (0.9%) carcinoma in-situ or invasive carcinoma. Similarly, 239 (26.6%) patients had nonneoplastic lesions. In colposcopy, high grade lesions were suspected more frequently in females of 41-50 years age group than in 31-40 years age group ( P < 0.01). Correlation between increasing age and dysplastic lesions were also observed ( P < 0.05). There was significant correlation between colposcopic diagnosis and histopathological diagnosis with a P value < 0.01. The sensitivity of colposcopy to diagnose dysplastic lesions were high 96.44% with positive predictive value of 62.65%. The specificity of colposcopy to diagnose various grades of dysplastic lesions is 34.98%. Conclusion: Colposcopy is highly sensitive method of screening dysplastic cervical lesions and should be used more frequently as a screening purpose.


Author(s):  
Mahdieh FARZANEHPOUR ◽  
Ahad MUHAMMADNEJAD ◽  
Setareh AKHAVAN ◽  
Mir Nader EMAMI RAZAVI ◽  
Somayeh JALILVAND ◽  
...  

Background: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer. Methods: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details. Results: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16. Conclusion: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.


2020 ◽  
Vol 7 (10) ◽  
pp. A502-508
Author(s):  
Niharika Rawat ◽  
Shivapriya Rajan

Background: Cervical cancer is the major cause of cancer deaths among women. Globally, around 5,70,000 new cases of cervical cancer and 3,11,000 deaths occurred in the year 2018. In India, Cervical cancer is a leading cause of cancer related mortality among women and the number of deaths is 60,000 per year among 97,000 diagnosed patients, especially those from lower socioeconomic group. Human Papilloma Virus (HPV) plays a crucial role in causing cervical dysplasia. This is done by upregulating p16INK4A, a cyclin dependent kinase inhibitor through interaction with cellular regulatory proteins. Hence p16INK4A can be used as a biomarker, since it is directly related variable for the presence of HPV. This study was conducted to evaluate the expression of p16INK4A in benign, premalignant and malignant cervical lesions and to assess its utility in diagnosing and grading cervical lesions. Methods: A total of 80 cervical specimens categorized histopathologically into nonspecific cervicitis, low grade squamous intraepithelial neoplasia (LSIL), high grade squamous intraepithelial neoplasia (HSIL) and squamous cell carcinoma cervix were included in this prospective study of one-year duration. Immunohistochemical study of p16INK4A were interpreted qualitatively and semi-quantitatively by Allred scoring system (0 to 8 points) which measures the proportion of stained cells and intensity of staining of cells. The collected data were statistically analyzed by ANOVA and chi square test. Result: Qualitative method showed absence of p16INK4A expression in all nonspecific cervicitis. 16.7% (2/12) LSIL, 100% (12/12) HSIL and 100% (28/28) squamous cell carcinoma cases showed p16INK4A positivity. Allred scoring of p16INK4A showed 66% (8/12) HSIL and 85.7% (24/28) squamous cell carcinoma cases with score 3 positivity. Hence high-grade lesions showed higher expression of this marker. Conclusion: IHC expression of p16INK4A showed increasing degree of expression from benign to premalignant and malignant lesions suggesting its diagnostic and prognostic value in the cervical cancer management


2014 ◽  
Vol 7 (2) ◽  
pp. 21-24 ◽  
Author(s):  
SR Tamrakar ◽  
CD Chawla

Aims: Cervical cancer is a major cause of morbidity and mortality in gynecology clients. It accounts for the most common cancer in women. A Papanicolaou (Pap) smear test (cervical cytology screening) is one of the best tests to screen for cervical cancer in its premalignant stage. The objective of this study is to find out the prevalence of abnormal Pap smear results and to determine the contributing factors for it. Methods: The out patient clinic register was reviewed. Out-patients clinic register from 1 Jan 2008 to 31 Dec 2011showed that a total of 25511 gynecology clients were seen. In these four years duration, a total of 1506 Pap smear samples were taken which accounted for 5.9% of the total gynecology clients. The samples were collected only after proper counseling and consent from the clients who visited the clinic for various gynecology complaints. Assumed predictors of abnormal Pap smear results were examined through inferential way (Chi square test) using Software SPSS version 13.0 for Windows. Results: The preliminary analysis showed the mean age was 37.57 ± 10.72 years (ranging from 18 to 81 years). Most of them were of Newar caste (28.7%), with 3 children (37.6%) and from Kavre District (66%). Most of them (343 clients) were of age group 30 – 34 years whereas 15.8, 10.8, 3.1 and 10.0 % (clients were of 40 – 44, 45 – 49, 50 – 54 and 55 above respectively. A total of 1062 samples were normal whereas 379 samples were suggestive of inflammatory and 39 samples were inadequate for evaluation. We had 22 samples suspicious for malignancy and/or low grade squamous intraepithelial lesion (LSIL) and 4 frank malignant cases. This accounted for 1.7% of total Pap smear samples. These cases were scheduled for colposcopic guided biopsies and histologic evaluations. There was significant difference between the age groups and Pap smear results (p=0.003) and parity with Pap smear results (p=0.000, highly significant). But there was no significant difference between caste and Pap smear results (p=0.166). Conclusions: There is no doubt that Pap test is one of the best and easiest tests to screen for precancerous and cancerous cervical lesions. In order to have a high yield it has to be combined with other alternative tests like HPV testing and/or visual inspection with acetic acid (VIA) or Lugol’s Iodine (VILI). Besides its use as screening tool, we can also evaluate for chronic cervicitis, sexually transmitted infection (STI), pelvic inflammatory disease (PID)and genital prolapse (if any) in same setting. Thus the community people will have broader benefits from the screening program. DOI: http://www.dx.doi.org/10.3126/njog.v7i2.11137   Nepal Journal of Obstetrics and Gynaecology / Vol 7 / No. 2 / Issue 14 / July-Dec, 2012 / 21-24


PRILOZI ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 143-151
Author(s):  
Vjosa A. Zejnullahu ◽  
Valon A. Zejnullahu ◽  
Slavica Josifovska ◽  
Nikola Vukovik ◽  
Kiril Pakovski ◽  
...  

AbstractTelomerase Reverse Transcriptase (TERT) is the main catalytic sub-unit of telomerase, a reverse transcriptase enzyme. Telomerase expression is regulated at many levels, with numerous studies suggesting that up-regulation of human TERT gene (hTERT) at transcriptional level results in immortal cell phenotype associated with cancer. The aim of this study is to determine the correlation between hTERT expression and different cervical precursor lesions, as well as with cervical cancer in patients with confirmed Human papillomavirus (HPV) infection.The study included molecular analyzes on cervical samples from 214 women and matched Papanicolaou (Pap) test results. HPV detection and genotyping was performed by polymerase chain reaction (PCR) and genotyping. Quantitative real-time PCR (qRT-PCR) was performed using TaqMan probes and were calculated relative to the reference gene.Results showed significantly increased hTERT mRNA expression levels in high-grade and low-grade lesions compared to normal control samples (p<0.01) associated with 6.31 fold higher risk for developing ASC-US and 9.20 for LSIL. Strong correlation between HPV infection and hTERT expression in the high-grade lesions and cervical cancer was also observed. hTERT relative expression values showed 98% specificity and 100 % sensitivity as indicator of cervical lesions particularly for the ACS-H, HSIL and cervical cancer. In conclusion, hTERT expression correlate with the cytological grade of the cervical lesions and HPV infection and has a potential to be used as a diagnostic and prognostic marker.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Juan Ramón Padilla-Mendoza ◽  
Arturo Contis-Montes de Oca ◽  
Mario Alberto Rodríguez ◽  
Mavil López-Casamichana ◽  
Jeni Bolaños ◽  
...  

Protein phosphorylation is a posttranslational modification that is essential for normal cellular processes; however, abnormal phosphorylation is one of the prime causes for alteration of many structural, functional, and regulatory proteins in disease conditions. In cancer, changes in the states of protein phosphorylation in tyrosine residues have been more studied than phosphorylation in threonine or serine residues, which also undergo alterations with greater predominance. In general, serine phosphorylation leads to the formation of multimolecular signaling complexes that regulate diverse biological processes, but in pathological conditions such as tumorigenesis, anomalous phosphorylation may result in the deregulation of some signaling pathways. Cervical cancer (CC), the main neoplasm associated with human papillomavirus (HPV) infection, is the fourth most frequent cancer worldwide. Persistent infection of the cervix with high-risk human papillomaviruses produces precancerous lesions starting with low-grade squamous intraepithelial lesions (LSIL), progressing to high-grade squamous intraepithelial lesions (HSIL) until CC is generated. Here, we compared the proteomic profile of phosphorylated proteins in serine residues from healthy, LSIL, HSIL, and CC samples. Our data show an increase in the number of phosphorylated proteins in serine residues as the grade of injury rises. These results provide a support for future studies focused on phosphorylated proteins and their possible correlation with the progression of cervical lesions.


2011 ◽  
pp. 144-153
Author(s):  
Dabeiba Adriana García ◽  
Ignacio Briceño ◽  
Marcos Castillo ◽  
Fabio Ancizar Aristizábal

Introduction: Cervical cancer is the second most common cancer among women worldwide and the second cause of cancer mortality in women. It has been demonstrated that the process of cervical carcinogenesis displays genetic and environmental epigenetic components. Currently, research is focused on new prognosis markers like oncogene amplification. Objectives: To perform detection of MYCN, C-MYC, MYCL1, ERBB2, EGFR, and AKT2 amplification. Additionally, to detect human papillomavirus in samples from normal cytology smear, cervical intraepithelial neoplasia (CIN) I, II, and III and cervical cancer patients. Methods: Papillomavirus (HPV) genotyping by reverse line blot (RLB) performed and gene amplification by detection with real-time PCR with Taqman probes. Results: HPV was present in 4% of the patients with normal cytology, 48% in CIN I, 63.6% in CIN II, 64% in CIN III, and 70.8% in cervical cancer. Genes amplified in cervical cancer were MYCN (39.1%), ERBB2 (34.7%), and MYCL1 (30.4%); showed higher amplification in high-grade lesions and cervical cancer in relation to low-grade lesions and normal cytology with statistically significant differences. Besides the genes, C-MYC, EGFR, and AKT2 were amplified in samples from patients with cervical cancer by 12%, 18%, and 13%, respectively; we did not find statistical differences. Conclusion: Higher prevalence of gene amplification and HPV was found in high-grade cervical lesions and cervical cancer.


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