P16 Methylation Is an Early Event in Cervical Carcinogenesis

2011 ◽  
Vol 21 (3) ◽  
pp. 452-456 ◽  
Author(s):  
Lee-Wen Huang ◽  
Hun-Shan Pan ◽  
Yu-Hung Lin ◽  
Kok-Min Seow ◽  
Heng-Ju Chen ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Promoter Methylation ◽  
Intraepithelial Neoplasia ◽  
Promoter Hypermethylation ◽  
Early Event ◽  
Low Grade ◽  
Neoplastic Progression ◽  
Frequent Event ◽  
Significant Difference ◽  
Low Grade Dysplasia

BackgroundAberrant gene promoter methylation is a critical event in tumorigenesis. The aim of this study was to explore the promoter hypermethylation of p16 and DAPK1 during the progression of cervical precancerous lesions.MethodsA series of 98 cervical neoplasms (72 cervical intraepithelial neoplasia and 26 cervical carcinomas) were evaluated. The promoter methylation status of p16 and DAPK1 was assessed from cervical scrapings by methylation-specific polymerase chain reaction.ResultsFor p16, the frequency of promoter hypermethylation showed an increasing trend from normal to dysplastic to invasive squamous cancer specimens, and this increase reached statistical significance (P < 0.0001). However, there was no significant difference in the promoter methylation state of DAPK1 with regard to the various grades of cervical lesions (P = 0.077). Specifically, methylation of p16 was a frequent event in the cervical carcinoma samples, and these figures were statistically significant compared with the normal and cervical intraepithelial neoplasia I cases (P = 0.015 and P = 0.021, respectively).ConclusionsThese results imply that promoter hypermethylation of p16 occurs at an early stage of cervical neoplastic progression. This early event may play an initiating role in the malignant transformation of low-grade dysplasia into high-grade dysplasia and invasive carcinoma. We suggest that aberrant promoter methylation of p16 may serve as a useful biomarker during the follow-up of low-grade dysplasia.

Extracellular regulated kinase-2 immunoreactivity increases in parallel with cervical intraepithelial neoplasia grade in cervical neoplasia

2008 ◽  
Vol 18 (3) ◽  
pp. 540-545
Author(s):  
V. KAPETANIOS ◽  
A. C. LAZARIS ◽  
P. BOGRIS ◽  
S. KOUNELI ◽  
A. NONNI ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Mapk Pathway ◽  
Statistical Significance ◽  
Intraepithelial Neoplasia ◽  
Early Event ◽  
Low Grade ◽  
High Grade ◽  
Cervical Lesions ◽  
Cin Iii ◽  
Extracellular Regulated Kinase

The cell cycle control system includes cyclins, cyclin-dependent kinases (CDK), and their inhibitors (CDK1). Extracellular regulated kinase (ERK1/2) (p44 and p42 mitogen-activated protein kinases [MAPKs]) is a component of the MAPK pathway, which is associated with cyclin D1 and CDK. It is a critical signaling system for the induction of cell proliferation, differentiation, and cell survival. The aim of this study was to investigate the usefulness of ERK2 expression as a marker of biological aggressiveness complementary to cervical intraepithelial neoplasia (CIN) grade as well as to compare its expression in preinvasive lesions with that in invasive carcinoma. Paraffin-embedded sections of 146 CIN lesions (32 CIN I, 49 CIN II, and 43 CIN III) and 22 invasive cervical carcinomas (13 squamous and 9 adenocarcinomas) were used for the standard immunohistochemical procedure with the application of the ERK2 monoclonal antibody. ERK2 staining displayed a cytoplasmic and nuclear pattern. The staining intensity was gradually increased according to the severity of the dysplastic lesions; ERK2 immunoreactivity was significantly increased in high-grade dysplastic lesions (CIN II and CIN III) and invasive carcinomas by comparison to low-grade dysplastic lesions (CIN I) (P < 0.001). When high-grade lesions were separately assessed, the differences between each one of them and CIN I retained their statistical significance: CIN II versus CIN I (P < 0.001) and CIN III versus CIN I (P < 0.001). In conclusion, our study found a direct relationship between the increasing grade of the dysplastic cervical lesions and the intensity of ERK2 staining, thus implying a role of ERK2 as an early event in cervical carcinogenesis.

scholarly journals P397 Surveillance in ulcerative colitis: Can we predict the risk for intraepithelial neoplasia?

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S368-S369
Author(s):  
J Estorninho ◽  
P Freire ◽  
S Lopes ◽  
M Ferreira ◽  
M Ferreira ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Duration ◽  
Intraepithelial Neoplasia ◽  
Screening Colonoscopy ◽  
Low Grade ◽  
Surveillance Colonoscopy ◽  
High Quality ◽  
Increased Risk ◽  
History Of ◽  
Low Grade Dysplasia

Abstract Background Ulcerative colitis (UC) has been associated with an increased risk of colorectal cancer (CRC). Although dye spray chromoendoscopy showed superiority to standard colonoscopy in surveillance studies, with the availability of higher-resolution colonoscopes, the utility of chromoendoscopy (CE) has been questioned. We aimed to evaluate the risk of intraepithelial neoplasia (IN) after a high-quality screening colonoscopy (making use of CE or random biopsies (RB) and removing all detected lesions) in a population with longstanding UC and to identify potential risk factors for dysplasia incidence. Methods In a previous study, 145 patients with clinically and endoscopic longstanding (≥8 yr) distal/extensive UC without primary sclerosing cholangitis and/or history of IN were prospectively randomised to undergo CE or RB. In this study, after a median follow-up of 5 additional years, we evaluated subsequent IN incidence in these patients, submitted to surveillance colonoscopy. Patients without high-quality surveillance colonoscopy (with good bowel preparation and cecum intubation) using high-definition were excluded. Results One hundred and twenty-one patients were included. Nine had removed adenomas with low-grade dysplasia in the index colonoscopy. Now, in surveillance colonoscopy, we detected 9 (7.4%) IN: low-grade dysplasia was found in 8 (6.6%) patients and a colorectal adenocarcinoma in 1 (0.008%) patient. After multivariate analysis, IN was significantly associated with older age (68 vs. 52 years, p &lt; 0.05) and higher disease duration (26 vs. 20 years, p &lt; 0.05). No association was found between IN and previous detection of IN in screening colonoscopy sex, the CE or RB use in index colonoscopy, extent of disease, The presence of pseudopolyps, smoking habits, familial history of CRC or maintenance therapy for UC. Conclusion In this study, older patients and higher disease duration were associated with a higher risk of IN in surveillance colonoscopy.

scholarly journals AYURVEDIC MANAGEMENT OF ATROPHIC VAGINITIS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA- A CASE REPORT

2020 ◽  
pp. 69-72
Author(s):  
Giby Thomas ◽  
Lakshmi Devi.R
Keyword(s):  
Case Report ◽  
Cervical Intraepithelial Neoplasia ◽  
Vaginal Discharge ◽  
Symptomatic Relief ◽  
Intraepithelial Neoplasia ◽  
Burning Sensation ◽  
Low Grade ◽  
Atrophic Vaginitis ◽  
Genital Area ◽  
Intraepithelial Lesion

Vaginitis in postmenopausal women is termed as atrophic vaginitis, characterised by vaginal bleeding or spotting, vaginal discharge and discomfort or dryness in vulva. As the symptoms are not usually disclosed by women it may become chronic and can adversely affect the quality of life. In cervical intraepithelial neoplasia the squamous epithelium of cervix is replaced by the cells of varying degree of atypia. Even though CIN1 and CIN2 regress spontaneously, untreated CIN1 and CIN2 lesions may progress to invasive carcinoma. Ayurvedic management for the above conditions focuses on symptomatic relief and improvement of general health and immunity. Oral medication and Sthanika Chikitsa like Kshara Karma and Varthi play vital role in this. A 70 year old lady presented with complaints of burning sensation and itching over genital area. On examination haemorrhagic spots were observed on vaginal walls. She was sent to Early Cancer Detection Centre for cytological screening. The reports showed low grade sqamous intraepithelial lesion. She was managed with oral medications and Sthanika chikitsa. During follow up she was relieved from the symptoms like burning sensation and itching over genital area and vaginal discharge. Bleeding spots on vaginal walls were absent and cytology revealed a negative smear for intraepithelial lesion or malignancy. From this case report it is evidenced that Ayurvedic treatment modality is effective and successful for the management of Atrophic vaginitis with CIN.

scholarly journals Analysis of smad4 gene promoter methylation in pancreatic and endometrial cancers

2017 ◽  
Vol 23 (2) ◽  
pp. 17-19
Author(s):  
Aleksandra Nikolic ◽  
Filip Opincal ◽  
Momcilo Ristanovic ◽  
Jovanka Trifunovic ◽  
Srbislav Knezevic ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Methylation Status ◽  
Gene Promoter ◽  
Promoter Hypermethylation ◽  
Surgical Removal ◽  
Smad4 Gene ◽  
Frequent Event ◽  
Cancer Types ◽  
Endometrial Cancers ◽  
Tumor Types

Background. Promoter hypermethylation of the SMAD4 gene has been registered in some cancer types, but in general doesn?t appear to be a frequent event in carcinogenesis. However, only a few published studies deal with this topic and not many cancer types have been analyzed. The aim of this study was to establish SMAD4 gene promoter methylation status in pancreatic and endometrial cancers. Methods. Patients included in the study (62 subjects) were diagnosed and surgically treated at the University of Belgrade, Clinical Center of Serbia. Patients with pancreatic carcinoma (17 subjects) underwent surgical removal of the pancreatic adenocarcinoma at the First Surgical Clinic, while the patients with endometrial carcinoma (45 subjects) underwent hysterectomy with adnexectomy at the Institute for Gynecology and Obstetrics. Extraction of DNA from fresh tissue samples was performed and the methylation status of the SMAD4 gene promoter was studied by a previously designed PCR-based HpaII and MspI restriction enzyme assay. The resulting PCR products were analyzed by electrophoresis in 2% agarose gels. Results. Neither of the analyzed samples was found to be hypermethylated. Conclusion. This is the first report on SMAD4 methylation status in pancreatic and endometrial tumor specimens, and supports the viewpoint that SMAD4 hypermethylation is not a common event in malignant tumors. Nevertheless, promoter hypermethylation remains a candidate mechanism for SMAD4 inactivation in malignant tissue as a potential cause of decreased or lost SMAD4 expression in certain tumor types, and should be further investigated in different tumor types and larger cohorts of patients.

scholarly journals Photodynamic Therapy for Low-grade Cervical Intraepithelial Neoplasia (CIN1): A Case Report

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Yinyin Zhang ◽  
Hong Lin ◽  
Huizhen Fan
Keyword(s):  
Photodynamic Therapy ◽  
Cervical Intraepithelial Neoplasia ◽  
Persistent Infection ◽  
Precancerous Lesions ◽  
Irradiation Time ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Cervical Canal ◽  
Low Grade ◽  
Oxygen Inhalation

As a drug-mechanical combination technology, photodynamic (PDT) can achieve accurate and targeted therapy for malignant tumors and benign diseases through the production of reactive oxygen species, oxygen free radicals or singlet oxygen by photosensitizers at specific wavelengths. Compared with traditional surgery, it has the advantages of selective killing, repeatable treatment, preserving target organ function and so on. The purpose of this study was to explore the clinical value of photodynamic therapy in cervical precancerous lesions by taking the patients with low-grade cervical intraepithelial neoplasia (CIN1) with high-risk human papillomavirus (HR-HPV) persistent infection diagnosed by "three-step diagnosis and treatment procedure" as an example. Using HiPorfin as a photosensitizer, photodynamic therapy was performed 48 hours after intravenous drip. Set laser wavelength 630nm, light dose density 137.58J/cm2, transmission efficiency 1.42, output power 2w. 3cm columnar optical fiber was placed around the 2cm in the cervical canal to cover all the lesions, and the irradiation time was 900s (600s in the cervical canal and 300s outside the cervical canal). The patients were given oxygen inhalation for 6 hours after operation, and the patients were observed for itching and other discomfort, and paid attention to avoid light. Photodynamic therapy was performed again in the same way on the second day. After two months of treatment, pathological biopsy showed chronic cervicitis, indicating that the disease had been effectively controlled. Theoretically, although the patient is not the absolute indication of photodynamic therapy (that is, meeting CIN ? or CIN ?, having fertility requirements and not undergoing surgery), this therapy can remove not only the superficial lesions inside and outside the cervix, but also the potential lesions not found under colposcopy. It can also block the persistent infection of HPV by inhibiting the expression of HPV18, E6 and E7mRNA in Hela cells. In combination with Baofukang suppository, it can block HPV infection. Increase the negative conversion rate of cervical HPV and reduce the probability of recurrence after CIN1 cure. For young female patients with persistent HR-HPV infection and fertility requirements, photodynamic therapy is an effective choice for clinical treatment of CIN1.

Endoscopic radiofrequency ablation or surveillance in patients with Barrett’s oesophagus with confirmed low-grade dysplasia: a multicentre randomised trial

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322082
Author(s):  
Maximilien Barret ◽  
Mathieu Pioche ◽  
Benoit Terris ◽  
Thierry Ponchon ◽  
Franck Cholet ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Randomised Trial ◽  
Barrett’S Oesophagus ◽  
Progression Rate ◽  
Low Grade ◽  
Neoplastic Progression ◽  
Barrett's Oesophagus ◽  
Ablation Therapy ◽  
Endoscopic Ablation ◽  
Low Grade Dysplasia

ObjectiveDue to an annual progression rate of Barrett’s oesophagus (BO) with low-grade dysplasia (LGD) between 9% and 13% per year endoscopic ablation therapy is preferred to surveillance. Since this recommendation is based on only one randomised trial, we aimed at checking these results by another multicentre randomised trial with a similar design.DesignA prospective randomised study was performed in 14 centres comparing radiofrequency ablation (RFA) (maximum of 4 sessions) to annual endoscopic surveillance, including patients with a confirmed diagnosis of BO with LGD. Primary outcome was the prevalence of LGD at 3 years. Secondary outcomes were the prevalence of LGD at 1 year, the complete eradication of intestinal metaplasia (CE-IM) at 3 years, the rate of neoplastic progression at 3 years and the treatment-related morbidity.Results125 patients were initially included, of whom 82 with confirmed LGD (76 men, mean age 62.3 years) were finally randomised, 40 patients in the RFA and 42 in the surveillance group. At 3 years, CE-IM rates were 35% vs 0% in the RFA and surveillance groups, respectively (p<0.001). At the same time, the prevalence LGD was 34.3% (95% CI 18.6 to 50.0) in the RFA group vs 58.1% (95% CI 40.7 to 75.4) in the surveillance group (OR=0.38 (95% CI 0.14 to 1.02), p=0.05). Neoplastic progression was found in 12.5% (RFA) vs 26.2% (surveillance; p=0.15). The complication rate was maximal after the first RFA treatment (16.9%).ConclusionRFA modestly reduced the prevalence of LGD as well as progression risk at 3 years. The risk-benefit balance of endoscopic ablation therapy should therefore be carefully weighted against surveillance in patients with BO with confirmed LGD.Trial registration numberNCT01360541.

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

2017 ◽  
Vol 21 (3) ◽  
pp. 171-176 ◽  
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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