Severe dysplasia can be distinguished from moderate and mild dysplasia of bronchial mucosa by changes in Ki-67 index

Abstract Background Early detection of dysplastic changes within oral potentially malignant disorders is the mainstay to prevent oral cancer. Ki-67 is one of the most useful antigens in this purpose. Aims The study aims were to recognize and mutually compare the proliferative status of idiopathic oral leukoplakia (OL) patches, which presented through different forms of dysplasia and carcinoma. Settings and Design In 4 years of observation, cumulatively 140 OL lesions were included for examination. The wholesome Ki-67 labeling scores in each of the subgroups were calculated. Subjects and Methods The World Health Organization recommended histopathological classification was used to categorize the dysplastic and malignant lesions. Paraffin-embedded tissue sections were processed for Ki-67 immunostaining. The labeling indices (LIs) were quantified semiquantitatively at the site of maximal reactive cells on tissue sections. Statistical Analysis The statistical comparison was performed by means of the SPSS software (Version 16.0 SPSS Inc.). A p-value < 0.05 was considered as the benchmark for statistical significance. Results A steady and significant increment in Ki-67 expression was discovered from dysplastic to malignant OL patches compared with normal mucosa. The labeling differences were significant between normal mucosa and mild dysplasia, as well as between mild, moderate, and severe dysplasia. However, the expression did not differ significantly with the severity of oral cancers. Conclusions Ki-67 is a useful molecular marker of carcinogenesis in OL. It also serves worthwhile in separating marginally dysplastic lesions, such as mild dysplasia or verrucous carcinoma from their benign epigones.

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Expression of p53, bcl-2, and ki-67 Proteins in the Inﬂammatory Regenerative and Dysplastic Epithelial Lesions of Flat Colonic Mucosa

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2006.3208 ◽

2008 ◽

Vol 6 (1) ◽

pp. 39-45 ◽

Cited By ~ 3

Author(s):

Svjetlana Radović ◽

Zora Vukobrat-Bijedić ◽

Ivan Selak ◽

Mirsad Babić

Keyword(s):

Cellular Proliferation ◽

P53 Protein ◽

Normal Mucosa ◽

Labelling Index ◽

Epithelial Dysplasia ◽

Severe Dysplasia ◽

Ki 67 ◽

Mild Dysplasia ◽

Sporadic Cases ◽

Epithelial Lesions

The aim of the study was to define the distribution of p53, bcl-2 and Ki-67 proteins in the inflammatory-regenerative and dysplastic lesionsof the colon mucosa. The relationship between the presentation of p53, bcl-2 and Ki-67 proteins and the intensity of the inflammatory-regenerative and dysplastic lesions in the colon flat mucosa was investigated as well. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions (108 mild, 58 moderate, and 30 severe dysplasia). The expression of all three proteins was assessed on the basis of location, quantity, and intensity of immunostaining, by counting antigen positive cells, in comparison with normal mucosa and adenocarcinoma. p53 protein appears only in sporadic cases (6.6%) of severe dysplasia. Bcl-2 expression appears significantly (p<0.005) more often in cases of mild dysplasia (61.1%) compared to inflammatory-regenerative mucosa (14.8%). In cases of mild dysplasia, bcl-2 positive cells were spreading from the lower third to the middle third of the crypts. Bcl-2 expression was maintained through the stadiums of moderate and severe dysplasia (75.8%), where antigen positive cells were found all along the crypts. A significant increase (p<0.005) in the expression of nuclear protein Ki-67 was noticed in the stadiums of moderate (labelling index =26.3) compared to mild dysplasia (labelling index=16.7), and severe (labelling index=36.7) compared to moderate dysplasia, where the zone of cellular proliferation was widen along the whole crypt length. In the process of the development of epithelial dysplasia in the flat mucosa of colon a degree of the gene p53 alteration is low and appears only in sporadic cases of severe dysplasia. Mutation of the bcl-2 gene is involved in the genesis of the lesion but not in its progression to carcinoma. Increased expressionof Ki-67 protein speaks in favour of an increased cellular proliferation which, together with the above mentioned mechanisms, is involved in the process of occurrence and progression of epithelial dysplasia in the flat mucosa of colon.

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Type IV collagen immunoreactivity of basement membrane in inflammatory-regenerative and dysplastic lesions of the flat colonic mucosa

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2003.3567 ◽

2003 ◽

Vol 3 (1) ◽

pp. 30-35

Author(s):

Svjetlana Radović ◽

Ivan Selak ◽

Mirsad Babić ◽

Željka Knežević ◽

Zora Vukobrat-Bijedić

Keyword(s):

Basement Membrane ◽

Colon Adenocarcinoma ◽

Normal Mucosa ◽

Collagen Iv ◽

Epithelial Dysplasia ◽

Collagen Type Iv ◽

Severe Dysplasia ◽

Colon Mucosa ◽

Mild Dysplasia ◽

Type Iv

The aim of this research is to establish by immunohistochemistry if there is a change in the expression of collagen type IV, as a substitute of basement membrane, in development of epithelial dysplasia in chronically inflamed colon mucosa.Methods. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases severe dysplasia, respectively. Visualisation of collagen IV and its way of expression within basement membrane of glandular crypts was performed by immunohistochemistry and then compared with findings in normal colon mucosa and colon adenocarcinoma tissue.Results. Changes in the expression of collagen IV comprised of its focal irregularities, diffuse thinning and/or thickening, focal interruptions or its complete absence. Significant changes in the expression of collagen IV in relation to normal mucosa already occur in inflammatory-regenerative mucosa. In mild dysplasia, these changes are more intensive in relation to those in inflammatory altered mucosa as well as at severe dysplasia in relation to moderate dysplasia. Changes in the expression of collagen IV in severe dysplasia are significantly more serious than in moderate dysplasia but are identical to those in colon adenocarcinoma tissue.Conclusion. These findings suggest that change in the expression of collagen IV is in correlation to a degree of epithelial dysplasia that developed in flat chronically inflamed colon mucosa.

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Probability of Transition of Normal Esophageal Mucosa and Precancerous Lesion to the Esophageal Cancer

10.21203/rs.3.rs-917455/v1 ◽

2021 ◽

Author(s):

Zhiyu Chen ◽

Yong YU ◽

Xue YANG ◽

Jing-Xuan WANG ◽

Wen-Qiang Wei ◽

...

Keyword(s):

Esophageal Cancer ◽

Carcinoma In Situ ◽

Markov Models ◽

Transition Probabilities ◽

Health State ◽

Severe Dysplasia ◽

Esophageal Mucosa ◽

Mild Dysplasia ◽

Pathological Stages

Abstract Background: To estimate the transition probabilities of esophageal cancer（EC） and its precancerous lesions by Markov model, which could provide important information for EC screening about choosing reasonable screening and follow-up intervals.Methods: The transition probabilities among pathological stages were estimated by establishing Markov models for the natural history of EC and repeatedly adjusting and calibrating Markov models by comparing the modeled incidence and distributions of pathological stages (alone or combined) with observed data in real-world condition. Results: In one year, the probabilities were 0.024, 0.05, 0.12 for people from health state progressing to mild dysplasia (mD), mild dysplasia (mD) to moderate dysplasia (MD), and moderate dysplasia (MD) to severe dysplasia/carcinoma in situ (SD/CIS), respectively. The age-specific transition probabilities were 0.08~0.18 for severe dysplasia/carcinoma in situ (SD/CIS) progressing to intramucosal carcinoma(IC), 0.4~0.87 for intramucosal carcinoma (IC) to submucosal carcinoma (T1N0M0) (SC), and 0.2~0.85 for submucosal carcinoma (T1N0M0) (SC) to invasive carcinoma (INC). The progression probabilities increased with age and the severity of the disease. Based on the estimated transition probabilities, we predicted the incidence of EC and distributions of its pathological stages. Comparisons between modeled results with observed data confirmed the validation of our transition probabilities.Conclusions: An esophageal cancer transition model in high-risk areas of China has been established with validity. It could be a point of reference for further economic evaluation and policy formulation of esophageal cancer screening.

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Correction of mildly dysplastic hips with periacetabular osteotomy demonstrates promising outcomes, achievement of correction goals, and excellent five-year survivorship

The Bone & Joint Journal ◽

10.1302/0301-620x.101b6.bjj-2018-1487.r1 ◽

2019 ◽

Vol 101-B (6_Supple_B) ◽

pp. 16-22 ◽

Cited By ~ 8

Author(s):

A. T. Livermore ◽

L. A. Anderson ◽

M. B. Anderson ◽

J. A. Erickson ◽

C. L. Peters

Keyword(s):

Outcome Measures ◽

Periacetabular Osteotomy ◽

Severe Dysplasia ◽

Free Survival ◽

Mild Dysplasia ◽

Significant Difference ◽

Patient Reported ◽

Radiological Measurements ◽

The Mean

Aims The aim of this study was to compare patient-reported outcome measures (PROMs), radiological measurements, and total hip arthroplasty (THA)-free survival in patients who underwent periacetabular osteotomy (PAO) for mild, moderate, or severe developmental dysplasia of the hip. Patients and Methods We performed a retrospective study involving 336 patients (420 hips) who underwent PAO by a single surgeon at an academic centre. After exclusions, 124 patients (149 hips) were included. The preoperative lateral centre-edge angle (LCEA) was used to classify the severity of dysplasia: 18° to 25° was considered mild (n = 20), 10° to 17° moderate (n = 66), and < 10° severe (n = 63). There was no difference in patient characteristics between the groups (all, p > 0.05). Pre- and postoperative radiological measurements were made. The National Institute of Health’s Patient Reported Outcomes Measurement Information System (PROMIS) outcome measures (physical function computerized adaptive test (PF CAT), Global Physical and Mental Health Scores) were collected. Failure was defined as conversion to THA or PF CAT scores < 40, and was assessed with Kaplan–Meier analysis. The mean follow-up was five years (2 to 10) ending in either failure or the latest contact with the patient. Results There was no significant difference in PROMs for moderate (p = 0.167) or severe (p = 0.708) groups compared with the mild dysplasia group. The numerical pain scores were between 2 and 3 units in all groups at the final follow-up (all, p > 0.05). There was no significant difference (all, p > 0.05) in the proportion of patients achieving target correction for the LCEA between groups. The mean correction was 12° in the mild, 15° in the moderate (p = 0.135), and 23° in the severe group (p < 0.001). Failure-free survival at five years was 100% for mild, 79% for moderate, and 92% for severely dysplastic hips (p = 0.225). Conclusion Although requiring less correction than hips with moderate or severe dysplasia, we found PAO for mild dysplasia to be associated with promising PROMs, consistent with that of the general United States population, and excellent survivorship at five years. Future studies should compare these results with the outcome after arthroscopy of the hip in patients with mild dysplasia. Cite this article: Bone Joint J 2019;101-B(6 Supple B):16–22.

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The Evaluation of Trochlear Osseous Morphology: An Epidemiologic Study

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967120s00441 ◽

2020 ◽

Vol 8 (7_suppl6) ◽

pp. 2325967120S0044

Author(s):

Sercan Yalçin ◽

Gabriel Onor ◽

Scott Kaar ◽

lee Pace ◽

Paolo Ferrua ◽

...

Keyword(s):

Correlation Coefficient ◽

Normal Population ◽

Trochlear Dysplasia ◽

Interobserver Reliability ◽

Intraclass Correlation ◽

Epidemiologic Study ◽

Intraobserver Reliability ◽

Severe Dysplasia ◽

Mild Dysplasia ◽

Study Population

Objectives: The purpose of this study is to investigate the prevalence of the trochlear dysplasia in our study population. Methods: We obtained 692 skeletally mature femoral specimens from the [Blinded Institution], [Blinded Collection]. Five observers were asked to evaluate each specimen for trochlear dysplasia on a scale between 0 and 3 (0 – normal/no dysplasia; 1 – mild dysplasia; 2 – moderate dysplasia; 3 – severe dysplasia). Each observer made initial evaluations for interobserver reliability. Each observer then re-evaluated each specimen one month later to determine intraobserver reliability. We evaluated inter and intraobserver reliability utilizing intraclass correlation coefficient (ICC). All statistics were performed with SPSS v.25 (IBM, USA). Results: The interobserver ICC of first and second evaluation of all observers were found to be 0.906 [0.894-0,916] and 0.904 [0.892-0.915], respectively. The intraobserver ICC of observers were as follows: Reviewer1: 0.799 [0.771-0.825]; Reviewer2: 0.686 [0.645-0.724]; Reviewer3: 0.808 [0.781-0.832]; Reviewer4: 0.787 [0.757-0.814]; Reviewer5: 0.778 [0.747-0.806]. These results show intra and interobserver correlation was good to excellent. The percentages of normal trochlea, mild dysplasia, moderate dysplasia and severe dysplasia for first evaluation, by reviewer, are as follows: Reviewer 1: 82.7%, 12.1%, 4.0%, 1.2%; Reviewer 2: 37.3%, 26.2%, 27.5%, 9.1%; Reviewer 3: 57.9%, 28.0%, 12.1%, 1.9%; Reviewer 4: 64.2%, 25.6%, 7.7%, 2.6%; Reviewer 5: 65.6%, 14.9%, 12.3%, 7.2%. The percentages of normal trochlea, mild dysplasia, moderate dysplasia and severe dysplasia for second evaluation, by reviewer, are as follows: Reviewer 1: 78.8%, 16.6%, 3.6%, 1.0%; Reviewer 2: 40.3%, 26.4%, 23.3%, 10.0%; Reviewer 3: 42.2%,35.1%, 18.8%, 3.9%; Reviewer 4: 57.4%, 31.9%, 8.2%, 2.5%; Reviewer 5: 73.7%, 8.2%, 9.7%, 8.4%. In total, the percentages of normal trochlea, mild dysplasia, moderate dysplasia and severe dysplasia were 60.00%, 22.51%, 12.72%, 4.77%; respectively. Conclusions: This study shows that although there was no absolute criteria to grade trochlear dysplasia, observers had similar opinions on the degree of dysplasia. Also, our cohort shows that moderate to severe dysplasia is not uncommon as it is present in around 17% of knees in our cohort. This is the first epidemiologic study evaluating the prevalence of trochlear dysplasia in the normal population.

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Complications and Short-Term Patient Outcomes of Periacetabular Osteotomy for Symptomatic Mild Hip Dysplasia

Hip International ◽

10.5301/hipint.5000420 ◽

2016 ◽

Vol 27 (1) ◽

pp. 42-48 ◽

Cited By ~ 18

Author(s):

Benjamin F. Ricciardi ◽

Kara G. Fields ◽

Catherine Wentzel ◽

Danyal H. Nawabi ◽

Bryan T. Kelly ◽

...

Keyword(s):

Functional Outcome ◽

Acetabular Dysplasia ◽

Periacetabular Osteotomy ◽

Harris Hip Score ◽

Severe Dysplasia ◽

Complication Rates ◽

Radiographic Findings ◽

Mild Dysplasia ◽

Early Functional Outcome ◽

Outcome Scores

Introduction The purpose of our study is to identify complications and early functional outcome scores in patients treated with periacetabular osteotomy (PAO) for mild acetabular dysplasia. Methods The study population consisted of patients from a single centre prospective hip registry undergoing PAO with mild acetabular dysplasia (LCEA ≥18° and ≤25°; n = 27 patients; Mild Dysplasia group). A comparison group of patients undergoing PAO with more severe acetabular dysplasia (lateral centre-edge angle [LCEA] ≤17°; n = 50 patients; Severe Dysplasia group) were included as a comparison cohort. Demographics, radiographic findings, complications, and functional outcome scores were recorded at 6 months, 1 year, and 2 years postoperatively (mean 15 months [range 6-30]). Results Demographic characteristics were similar in patients with mild dysplasia undergoing PAO compared with more severe dysplasia. Achievement of radiological correction and complication rates were not different between the 2 groups. Functional outcome scores showed similar improvements in modified Harris Hip Score (mHHS), hip outcome score (HOS) activities of daily living (ADL), HOS Sport, and the international Hip Outcome Tool-33 (iHOT-33) at all time points between the 2 groups with over 90% of patients in the mild dysplasia group achieving a minimum important change (MIC) in functional outcome scores at final follow-up. Discussion Patients with symptomatic mild acetabular dysplasia undergoing PAO have similar complication rates and functional outcomes as a cohort of patients with more severe dysplasia.

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Estimation of The Transitional Probability Among Esophageal Cancer and Its Precancerous Lesions

10.21203/rs.3.rs-76203/v1 ◽

2020 ◽

Author(s):

Yong YU ◽

Yue XIE ◽

Xue YANG ◽

Jing-Xuan WANG ◽

Zhi-Yu CHEN ◽

...

Keyword(s):

Esophageal Cancer ◽

Carcinoma In Situ ◽

Markov Models ◽

Transition Probabilities ◽

Precancerous Lesions ◽

Health State ◽

Severe Dysplasia ◽

Mild Dysplasia ◽

Pathological Stages

Abstract Background: To estimate the transition probabilities of esophageal cancer (EC) and its precancerous lesions during the process of canceration by Markov model, which could provide important information for EC screening with regard to choosing reasonable screening and follow-up intervals.Methods: The transition probabilities among pathological stages were estimated by establishing Markov models for the natural history of EC and repeatedly adjusting and calibrating Markov models through comparing the modeled incidence and distributions of pathological stages (alone or combined) with observed data in real world condition. Results: In one year, the probabilities were 0.024, 0.05, 0.12 for people from health state progressing to mild dysplasia (mD), mild dysplasia (mD) to moderate dysplasia (MD), and moderate dysplasia (MD) to severe dysplasia/carcinoma in situ (SD/CIS), respectively. The age-specific transition probabilities were 0.08~0.18 for severe dysplasia/carcinoma in situ (SD/CIS) progressing to intramucosal carcinoma(IC), 0.4~0.87 for intramucosal carcinoma (IC) to submucosal carcinoma (T1N0M0) (SC), and 0.2~0.85 for submucosal carcinoma (T1N0M0) (SC) to invasive carcinoma (INC). The progression probabilities increased with age and the severity of the disease. Based on the estimated transition probabilities, we predicted the incidence of EC and distributions of its pathological stages. Comparisons between modeled results with observed data confirmed the validation of our transition probabilities.Conclusion: The estimating transition probabilities of EC and its precancerous lesions were reliable and could be used to address questions such as the optimal screening frequency, screening intervals, and health economic evaluation of screening strategies.

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Class-specific herpes simplex virus antibodies in sera and cervical secretions from patients with cervical neoplasia: a multi-group comparison

Epidemiology and Infection ◽

10.1017/s0950268800067194 ◽

1988 ◽

Vol 100 (3) ◽

pp. 455-465 ◽

Cited By ~ 6

Author(s):

G. E. Dale ◽

R. M. Coleman ◽

J. M. Best ◽

B. B. B. Benetato ◽

N. C. Drew ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Cervical Dysplasia ◽

Secretory Iga ◽

Severe Dysplasia ◽

Mild Dysplasia ◽

Serum Igg ◽

Serum Iga ◽

Caucasian Women ◽

Simplex Virus

SummarySerum and cervical secretions were collected from patients with cervical dysplasia, carcinoma-in-situ (CIS), squamous cell carcinoma (cervical SCC), and controls with normal cervices, attending clinics within the West Lambeth Health District, London. Enzyme-linked immunosorbent assays were used to examine cervical secretory IgA (sIgA) and serum IgG and IgA antibodies to herpes simplex virus (HSV). Sexual and demographic factors were considered during data analysis, which involved fitting multiple linear or multiple logistic regressions to HSV antibody levels. Prevalence of sIgA-HSV and levels of serum antibodies to HSV in all groups were compared with those of gynaecology controls. Caucasian women with mild dysplasia had a significantly higher prevalence of sIgA-HSV. Serum IgG levels to HSV (IgG-HSV) were significantly elevated in women with mild dysplasia and severe dysplasia/ClS. Serum IgA levels to HSV1 (IgG-HSV1) were significantly higher in women with cervical SCC (after adjusting for smoking habits) and other genital tumours. Significantly higher levels of serum IgA to HSV2 (IgA-HSV2) were also found among Caucasian women with cervical SCC. The possible role of HSV as a co-factor in cervical carcinogenesis is discussed.

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Natural History Analysis of 101 Severe Dysplasia and Esophageal Carcinoma Cases by Endoscopy

Gastroenterology Research and Practice ◽

10.1155/2017/9612854 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Jin-Wu Wang ◽

Chen-Tao Guan ◽

Li-Li Wang ◽

Ling-Yun Chang ◽

Chang-Qing Hao ◽

...

Keyword(s):

Natural History ◽

Population Based ◽

Progression Rate ◽

Severe Dysplasia ◽

Mild Dysplasia ◽

History Analysis ◽

Screening Protocol ◽

Screening Intervals ◽

The Mean

Objectives. Our research is to realize the natural history from dysplasia to carcinoma and to provide evidence for exploring proper screening intervals. Methods. After the onset endoscopy screening, 2093 of the patients participated in the endoscopic follow-up voluntarily. Totally, 101 severe dysplasia and carcinoma cases, either diagnosed in the first endoscopy without treatment or diagnosed in the second endoscopy, were included in our study. We compared the pathologic results of their two endoscopies and calculate the mean and median progression time. Results. Of the 39 severe dysplasia cases diagnosed by the onset endoscopy, only 8 progressed to carcinoma. For severe dysplasia cases diagnosed by the follow-up endoscopy, mean progression times are 55.0, 49.8, and 38.0 months and median progression times are 43, 56, and 31 months for esophagitis, mild dysplasia, and moderate dysplasia, respectively. For superficial carcinoma cases diagnosed by the second endoscopy, mean progression times are 76.0, 57.4, and 47.0 months and median progression times are 77, 63, and 35 months for mild dysplasia, moderate dysplasia, and severe dysplasia, respectively. Conclusions. Population-based severe dysplasia cases may have much lower carcinoma progression rate than specific-selected ones. The progression time for most enrolled cases seems longer than that of the recent screening protocol recommended.

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