Expression and clinical significance of estrogen receptor, progesterone receptor, p53 and p16 protein in endometrial carcinoma / 中国基层医药

Objective:To investigate the expression and clinical significance of estrogen receptor (ER), progesterone receptor (PR), p53 and p16 protein in endometrial carcinoma.Methods:The endometrial tissue of 57 patients with endometrial carcinoma who received surgery in The First People's Hospital of Chuzhou between January 2017 and May 2021 was harvested as the study group. The normal endometrial tissue of 30 patients with endometrial hyperplasia was selected as the control group. Envision immunohistochemical staining was performed to determine the expression of ER, PR, p53 and p16 protein in endometrial tissue and analyze their expression with clinical pathological characteristics.Results:ER, PR, p16 protein expression rates in the endometrial tissue in the study group were 70.2%, 61.4%, 38.6%, respectively, which were significantly lower than 90.0%, 86.7%, 93.3% in the control group ( χ2 = 4.36, 5.98, 24.09, all P < 0.05). p53 expression rate in the endometrial tissue was significantly higher in the study group than that in the control group (52.6% vs. 13.3%, χ2 = 12.75, P < 0.001). ER and PR expression were significantly different between endometrial carcinoma patients with lymph node metastasis and those without and among those with different histological grades and those at different pathological stages (all P < 0.05). There was no significant difference in p53 protein expression among patients with different pathological stages of endometrial carcinoma, between patients who suffered endometrial carcinoma at different ages, and between patients with different degrees of myometrial invasion (all P > 0.05). p16 protein expression rate differed among patients with different pathological stages of endometrial carcinoma, among those with different histological grades and between patients with different degrees of myometrial invasion (all P < 0.05). There was no significant difference in p16 protein expression rate between endometrial carcinoma patients with lymph node metastasis and those without ( P > 0.05). Conclusion:Abnormal expressions of ER, PR, p53 and p16 protein in endometrial tissue may be related to the occurrence, development and transformation of the disease. Combined detection of ER, PR, p53 and p16 protein is helpful for the clinical diagnosis, treatment and prognosis assessment of endometrial carcinoma.

Presença do papilomavirus humano tipo 16 e expressão gênica da proteína p16ink4a e oncoproteína e7 no carcinoma colorretal / Hpv16 and expression of protein p16ink4a and e7 oncoprotein in colorectal carcinoma

RESUMO - INTRODUÇÃO: O papilomavírus humano (HPV) é agente das doenças sexualmente transmissíveis de maior prevalência no mundo que estão associadas ao câncer do colo do útero e canal anal. A ação do HPV na carcinogênese colorretal não está ainda estabelecida. OBJETIVO: Estudar a eventual correlação entre a presença do HPV tipo 16 e a expressão gênica da proteína p16INK4a e da oncoproteína E7 de HPV e de seus níveis no tecido do carcinoma colorretal. METODOS: Estudo retrospectivo caso-controle de 79 doentes com carcinoma colorretal divididos em dois grupos: HPV presente e HPV ausente. Foi realizada reação em cadeia da polimerase (PCR), além da hibridização do tipo dot blot para o HPV 16 e o HPV 18 Amostras do tecido colorretal também foram submetidas ao estudo imuno-histoquimico para avaliar o nível tecidual das proteínas E7 e p16INK4a. RESULTADOS: O HPV foi identificado em 36 (45,6%) casos. Não houve diferença significante entre os grupos quanto ao sexo (p=0,056), idade (p=0,1), localização cólica e/ou retal (0,098) e presença do HPV. A expressão gênica da oncoproteína E7 de HPV estava presente em 3,12% dos casos (p=0,9) e a expressão da proteína p16INK4a foi observada em 46,3% (p=0,27) dos indivíduos com detecção do HPV. CONCLUSÃO: A expressão gênica e os níveis teciduais da oncoproteína E7 e da proteína p16INK4a encontrados nos pacientes positivos para o HPV sugerem a ausência de atividade oncogênica do HPV tipo 16 no carcinoma colorretal.

ABSTRACT - BACKGROUND: Human papillomavirus (HPV) is the agent of the most prevalent sexually transmitted diseases in the world associated with cervix and anal canal cancer. The action of HPV on colorectal carcinogenesis is not yet established. OBJECTIVE: This research aimed to study the possible correlation between the presence of HPV16 and the gene expression of p16INK4a protein and HPV E7 oncoprotein and their levels in colorectal carcinoma tissue. METHODS: A retrospective case-control study of 79 patients with colorectal carcinoma was divided into two groups: HPV-positive and HPV-negative. The polymerase chain reaction was performed, in addition to dot-blot hybridization for HPV16 and HPV18. Colorectal tissue samples were also subjected to immunohistochemical study to assess the tissue level of E7 and p16INK4a proteins. RESULTS: HPV was identified in 36 (45.6%) cases. There was no significant difference between groups regarding gender (p=0.056), age (p=0.1), colic and/or rectal location (0.098), and presence of HPV. Gene expression of HPV E7 oncoprotein was present in 3.12% of cases (p=0.9), and p16INK4a protein expression was observed in 46.3% (p=0.27) of those selected with HPV detection. CONCLUSION: Gene expression and tissue levels of E7 oncoprotein and p16INK4a protein found in HPV-positive patients suggest the absence of HPV16 oncogenic activity in colorectal carcinoma.

Is there correlation between human papillomavirus (hpv) and esophageal epidermoid carcinoma? / Há correlação entre o papilomavírus humano (hpv) e o carcinoma epidermoide de esôfago?

ABSTRACT Background: Currently, persistent human papillomavirus (HPV) infection has been related in some geographic regions as a risk factor for esophageal squamous cell carcinoma. It results in the immunoexpression of the p16 protein, which has been used as marker of the oncogenic lineage by this etiological agent. Aim: To correlate epidemiological aspects of esophageal squamous cell carcinoma with the prevalence of HPV infection. Methods: Fifty-eight cases were analyzed and submitted to histopathological and immunohistochemical analysis by p16. Results: Of the 58 cases evaluated, 40 were men and 18 women, with a mean age of 63.2 years. p16 immunoexpression was positive in 46.55%. Conclusion: The prevalence of HPV infection is high in esophageal squamous cell carcinoma presenting in almost half of the cases (46.55%), without gender differentiation.

RESUMO Racional: Atualmente a infecção persistente pelo papilomavírus humano (HPV) tem sido relacionada em algumas regiões geográficas como fator de risco para o carcinoma epidermoide do esôfago. Ela resulta na imunoexpressão da proteína p16, que tem sido utilizada como marcadora da linhagem oncogênica por este agente etiológico. Objetivo: Correlacionar aspectos epidemiológicos do carcinoma epidermoide do esôfago com a prevalência de infecção pelo HPV. Métodos: Foram analisados 58 casos buscando-se perfil epidemiológico dos pacientes, com suas peças submetidas à análise histopatológica e imunoistoquímica pelo p16. Resultado: Dos 58 casos avaliados, 40 eram homens e 18 mulheres, com idade média de 63,2 anos. A imunoexpressão pelo p16 foi de 46,55%. Conclusão: A prevalência de infecção pelo HPV é alta no carcinoma epidermoide de esôfago apresentando-se em quase a metade dos casos (46,55%), sem diferenciação de idade quanto aos gêneros.

Clinical value of P16 and Ki-67 expressions in cervical biopsy for predicting early cervical cancer in patients with high-risk HPV infection / 中国基层医药

Objective@#To explore the positive expressions of P16 and Ki-67 proteins in cervical biopsy lesions of patients with high-risk HPV infection and abnormal detection of liquid-based thin-layer cytology test(TCT), and the clinical value in predicting occurrence of early cervical cancer.@*Methods@#A total of 120 patients with high-risk HPV infection(16 and 18 subtypes positive) and abnormal TCT in the Traditional Chinese Medicine Hospital of Linhai from January 2016 to July 2017 were enrolled in the study.The colposcopy was used to get cervical biopsy lesions for pathological diagnosis, immunohistochemical staining was used to detect P16 and Ki-67 proteins.@*Results@#There were up to 66 patients with HPV-16 positive, 34 cases with HPV-18 positive, other 20 cases with 16 and 18 positive; 6 cases of atypical squamous epithelial cells(ASC), 46 cases of low-grade squamous intraepithelial lesions (LSIL), 60 cases of high-grade SIL(HSIL), other 8 cases of cervical squamous cell carcinoma(SCC) were diagnosed by TCT; 5 cases of inflammation, 105 cases of CIN and 10 cases of SCC by pathologically diagnosis.The positive rates of P16 and Ki-67 proteins were gradually increased in patients with inflammation, CIN and SCC[0(0/5), 36.2%(38/105), 70.0%(7/10), χ2=4.382, P=0.036; 0(0/5), 40.0%(42/105), 80.0%(8/10), χ2=5.945, P=0.015]. The patients with CIN were followed up for 21~36 months, median time 29.5 months.Twenty-six patients progressed to SCC, at the end of follow-up, the positive rates of P16 and Ki-67 proteins in patients with SCC were significantly higher than those in the CIN patients without progress[61.5%(16/26) vs.39.2%(31/79), χ2=3.934, P=0.047; 69.2%(18/26) vs.41.8%(33/79), χ2=5.905, P=0.015].@*Conclusion@#The positive expression rates of P16 and Ki-67 proteins in cervical biopsy tissues are significantly higher in patients with high-risk HPV infection and abnormal TCT, which in patients with pathologically diagnosis of SCC are higher than CIN patients, the same results in CIN patients with SCC progression than non-progressing patients, suggesting that P16 and Ki-67 proteins are of great value in predicting occurrence of early cervical cancer.

Clinical value of P16 and Ki-67 expressions in cervical biopsy for predicting early cervical cancer in patients with high-risk HPV infection / 中国基层医药

Objective To explore the positive expressions of P 16 and Ki -67 proteins in cervical biopsy lesions of patients with high-risk HPV infection and abnormal detection of liquid -based thin-layer cytology test (TCT),and the clinical value in predicting occurrence of early cervical cancer .Methods A total of 120 patients with high-risk HPV infection(16 and 18 subtypes positive) and abnormal TCT in the Traditional Chinese Medicine Hospital of Linhai from January 2016 to July 2017 were enrolled in the study.The colposcopy was used to get cervical biopsy lesions for pathological diagnosis ,immunohistochemical staining was used to detect P 16 and Ki-67 proteins. Results There were up to 66 patients with HPV-16 positive,34 cases with HPV-18 positive,other 20 cases with 16 and 18 positive;6 cases of atypical squamous epithelial cells (ASC),46 cases of low-grade squamous intraepithelial lesions (LSIL),60 cases of high-grade SIL(HSIL),other 8 cases of cervical squamous cell carcinoma (SCC) were diagnosed by TCT;5 cases of inflammation,105 cases of CIN and 10 cases of SCC by pathologically diagnosis.The positive rates of P16 and Ki-67 proteins were gradually increased in patients with inflammation ,CIN and SCC[0(0／5),36.2%(38／105),70.0%(7／10),χ2 ＝4.382,P＝0.036;0 (0／5),40.0%(42／105),80.0%(8／10),χ2 ＝5.945,P＝0.015].The patients with CIN were followed up for 21～36 months,median time 29.5 months.Twenty-six patients progressed to SCC ,at the end of follow-up,the positive rates of P16 and Ki-67 proteins in patients with SCC were significantly higher than those in the CIN patients without progress [61.5%(16／26) vs.39.2%(31／79), χ2 ＝3.934,P＝0.047;69.2%(18／26) vs.41.8%(33／79),χ2 ＝5.905,P＝0.015].Conclusion The positive expression rates of P16 and Ki-67 proteins in cervical biopsy tissues are significantly higher in patients with high -risk HPV infection and abnormal TCT ,which in patients with pathologically diagnosis of SCC are higher than CIN patients,the same results in CIN patients with SCC progression than non -progressing patients,suggesting that P16 and Ki-67 proteins are of great value in predicting occurrence of early cervical cancer .

Significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma of the larynx / 中华病理学杂志

Objective@#To study the significance of HPV and cell cycle related proteins in basaloid squamous cell carcinoma (BSCC) of the larynx.@*Methods@#Twenty-nine cases of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December 2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR-RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry were performed. The relationship between these indicators, various pathologic parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status was analyzed.@*Results@#There were 27 male and 2 female patients. The median age was 62 years. Lymph node metastasis and supraglottic tumor location were slightly higher than that of "usual" SCC, but not statistically significant (P>0.05). HPV DNA was detected in 27.6% (8/29) of the laryngeal BSCC, and all were HPV16. The expression of HPV was not related to age, alcohol consumption, tumor stage and tumor size. p53 was expressed in 31.0%(9/29) of laryngeal BSCC, and these cases were more likely supraglottic and had lymph node metastases (P<0.05). p16 staining was seen in 24.1% (7/29) of laryngeal BSCC, and these cases showed slightly higher rate of lymph node metastasis compared to p16 negative cases. The expression rates of p21 and cyclinD1 were 27.6% (8/29) and 69.0%(20/29), respectively, which were not related to age, tumor size, stage, lymph node metastasis, smoking and drinking. There were only 3 p16+ /HPV+ cases, which showed higher p21 and Ki-67 index compared to the HPV negative group (P<0.05).@*Conclusion@#Some laryngeal BSCC expresses HPV DNA, possibly indicating an association with HPV; but p16 expression is not a reliable indicator for HPV infection.

Expression of programmed death-ligand 1, topoisomerase Ⅱα and p16 proteins in cervical cancer and their significances / 肿瘤研究与临床

Objective To analyze the expression of programmed death ligand 1 (PD-L1),p16 proteins and DNA topoisomerase Ⅱ α (TOPO Ⅱ α) in cervical cancer and their clinical significances.Methods A total of 181 paraffin-embedded operating specimens and the biopsy including 106 cervical squamous cell carcinoma,30 high grade cervical intraepithelial neoplasia (CIN),30 low grade CIN and 33 normal cervical were selected from January 2014 to December 2015.An immunohistochemical EnVision method was used to detect the expression of PD-L1,p16 and TOPO Ⅱ α.Results The positive rate of PD-L1 expression in cervical squamous cell carcinoma was 66.0 ％ (70/106),but it was not expressed in high grade CIN,low grade CIN and normal cervical tissues,the differences were statistically significant (all P =0.000).Whereas,in squamous cell carcinoma,the positive rate of PD-L1 in poor differentiation group [77.3 ％ (51/66)] was higher than that in middle or high differentiation group [56.5 ％ (21/40)],and the difference was statistically significant (x2 =7.02,P =0.01).According to the FIGO stage,the positive rate in stage Ⅰ-Ⅱ group [54.9 ％ (28/51)] was lower than that in stage Ⅲ-Ⅳ group [76.4 ％ (42/55)],and the difference was statistically significant (x2 =5.47,P =0.02).But there was no statistical significance in lesion size or lymph node metastasis (both P ＞ 0.05).The positive rate of p16 in cervical squamous cell carcinoma was 99.1％ (105/ 106),in high grade CIN was 86.7 ％ (26/30),in low grade CIN was 26.7 ％ (8/30),and no expression in normal cervical tissues,the differences were statistically significant (all P ＜ 0.001).The expression of p16 had no relationship with histological differentiation,FIGO stage,lesion size,and lymph node metastasis (all P ＞ 0.05).The positive expression rate of TOPO Ⅱ α in cervical squamous cell carcinoma was 97.2 ％ (103/106),compared with that in high grade CIN [73.3 ％ (22/30)],low grade CIN [66.7 ％ (20/30)],and normal cervical tissues (no expression),the differences were statistically significant (all P =0.000).But there was nosignificant difference in the positive expression rate of TOPOⅡ α between high grade and low grade CIN (x2 =0.32,P =0.570).The expression of TOPO 1Ⅱ α had no relationship with histological differentiation,FIGO stage,lesion size and lymph node metastasis (all P ＞ 0.05).Conclusion The expression of PD-L1,p16 and TOPO Ⅱ α is associated with the invasion of cervical cancer.PD-L1 may be an immune checkpoint for the treatment of patients with invasive cervical cancer.

Sorting role of p16INK4a/Ki-67 double immunostaining in the cervical cytology specimens of ASCUS and LSIL cases / 中华病理学杂志

Objective@#To investigate the sorting effect of p16INK4a/Ki-67 double immunostaining method in patients with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology results.@*Methods@#Four-hundred and twenty cases collected during April 2014 to February 2015 of cervical cytology of ASCUS (n=318) and LSIL (n=102) were selected, and residual liquid-based cytology specimens were used for p16INK4a/Ki-67 double immunostaining. The sensitivity and specificity of the detection of cervical precancerous lesions and cervical cancer were calculated, and the results were compared with high risk HPV. Taking histological follow-up as the gold standard, the test was considered positive when at least one cell exhibited p16INK4a/Ki-67 co-staining, without requirement of adjunct morphologic interpretation of positive cells.@*Results@#Further screening CIN2+ in cytology ASCUS and LSIL group , the sensitivity of p16INK4a/Ki-67 double immunostaining was slightly lower than high risk HPV (84.2% vs. 94.7%), while the specificity was higher (84.0% vs. 53.9%). For ASCUS patients, the sensitivity of p16INK4a/Ki-67 double immunostaining and high risk HPV was 82.6% and 91.3%, and the specificity was 88.8% and 63.7%, respectively. For LSIL patients, the sensitivity of p16INK4a/Ki-67 double immunostaining and high risk HPV was 86.7% and 100.0%, and the specificity was 67.8% and 20.7%, respectively. For patients younger and older than 30 years, specificity of p16INK4a/Ki-67 double immunostaining was both higher than that of high risk HPV (80.8% vs. 42.3%; 84.6% vs. 56.9%).@*Conclusions@#p16INK4a/Ki-67 double immunostaining can effectively identify the high risk population in ASCUS or LSIL, with higher specificity than high risk HPV test. p16INK4a/Ki-67 double immunostaining may benefit patients younger than 30 years of age as a preliminary or potential cytology-combining screening tool.

Expression of Ki-67 and P16 INK4a in chemically-induced perioral squamous cell carcinomas in mice / Expressão KI-67 e P16 INK4a em carcinomas espinocelulares periorais quimicamente induzidos em camundongos

ABSTRACT Objective: to evaluate the influence of Ki-67 and P16INK4a proteins immunohistochemical expressions on the clinical and morphological parameters of perioral squamous cell carcinoma induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) in mice. Methods: we topically induced the lesions in the oral commissure of ten Swiss mice for 20 weeks, determining the time to tumors onset and the average tumor volume up to 26 weeks. In histopathological analysis, the variables studied were histological malignancy grade and the immunohistochemical expression of Ki-67 and P16INK4a proteins. The correlation between variables was determined by application of the Spearman correlation test. Results: the mean time to onset of perioral lesions was 21.1 ± 2.13 weeks; mean tumor volume was 555.91 ± 205.52 mm3. Of the induced tumors, 80% were classified as low score and 20% high score. There was diffuse positivity for Ki-67 in 100% of lesions - Proliferation Index (PI) of 50.1 ± 18.0. There was a strong direct correlation between Ki-67 immunoreactivity and tumor volume (R = 0.702) and a low correlation with the malignancy score (R = 0.486). The P16INK4a protein expression was heterogeneous, showing a weak correlation with tumor volume (R = 0.334). There was no correlation between the immunohistochemical expression of the two proteins studied. Conclusion: in an experimental model of DMBA-induced perioral carcinogenesis, tumor progression was associated with the tumor proliferative fraction (Ki-67 positive cells) and with tumor histological grading, but not with P16INK4a expression.

RESUMO Objetivo: avaliar a influência da expressão imuno-histoquímica das proteínas Ki-67 e p16INK4a sobre parâmetros clínico-morfológicos em carcinomas espinocelulares periorais quimicamente induzidos com 9,10-dimetil-1,2-benzantraceno (DMBA) em modelo murino. Métodos: as lesões foram induzidas topicamente na comissura labial de dez camundongos Swiss durante 20 semanas, sendo determinado o momento de surgimento dos tumores e volume tumoral médio até 26 semanas. Na análise histopatológica, as variáveis estudadas foram gradação histológica de malignidade tumoral e expressão imuno-histoquímica das proteínas Ki-67 e p16INK4a. A correlação entre as variáveis estudadas foi determinada pela aplicação do teste de correlação de Spearman. Resultados: o tempo médio de surgimento das lesões periorais foi 21,1±2,13 semanas. Volume tumoral médio foi de 555,91±205,52mm3. Dos tumores produzidos, 80% foram classificados como de baixo escore e 20%, alto escore. Evidenciou-se positividade difusa para Ki-67 em 100% das lesões - índice de marcação (PI) de 50,1±18,0. Verificou-se correlação direta forte entre a imunoexpressão do Ki-67 e o volume tumoral (R=0,702) e fraca correlação com o escore de malignidade (R=0,486). A expressão da proteína p16INK4a foi heterogênea, mostrando fraca correlação com o volume tumoral (R=0,334). Não houve correlação entre a expressão imuno-histoquímica das duas proteínas estudadas. Conclusão: Em modelo experimental de carcinogênese perioral DMBA-induzida, a progressão tumoral está associada à fração proliferativa do tumor (células ki-67 positivas) e com a gradação histológica tumoral, porém não com a expressão da p16INK4a.

Effects of HBV X protein on expression and promoter methylation of p16 tumor suppressor gene / 临床肝胆病杂志

ObjectiveTo explore the effects of hepatitis B virus X protein (HBx) on the expression and promoter methylation of the p16 tumor suppressor gene, and to investigate the epigenetic role of HBx in the development and progression of hepatitis B virus (HBV)-associated hepatocellular carcinomas (HCC). MethodsExperiments were performed in the human hepatoblastoma cell line HepG2, HepG2 cells expressing green fluorescent protein (HepG2/GFP), and HepG2 cells stably expressing GFP-HBx fusion protein (HepG2/GFP-HBx). Western blot was used to determine the expression levels of the p16 protein in HepG2 cells, HepG2/GFP cells, and HepG2/GFP-HBx cells. HepG2/GFP-HBx cells were treated with a universal inhibitor of DNA methyltransferase (DNMT), 5-aza-2'-deoxycytidine (5-aza-2'-dC). Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation of the p16 tumor suppressor gene in HepG2 cells, HepG2/GFP cells, and HepG2/GFP-HBx cells treated with or without 5-aza-2′-dC. Multiple-group comparison was made by analysis of variance. ResultsAccording to the results of Western blot, HepG2/GFP-HBx cells had a significantly lower expression level of the p16 protein than HepG2 cells and HepG2/GFP cells (P=0.0007; P=00014); there was no significant difference in the expression level of the p16 protein between HepG2/GFP and HepG2 cells (P＞0.05). The MSP assay revealed partial CpG methylation in the p16 promoter region in HepG2/GFP-HBx cells. No promoter methylation was detected in HepG2 cells or HepG2/GFP cells. Non-methylation in the p16 promoter region was restored in HepG2/GFP-HBx cells treated with 5-aza-2′-dC. ConclusionIn the hepatoblastoma cell line, HBx down-regulates the expression of the p16 tumor suppressor gene by inducing methylation in its promoter region. The DNMT inhibitor, 5-aza-2′-dC, restores non-methylation in the p16 promoter region. The reversible modification provides new insights for the treatment and prevention of HBV-associated HCC.

Biologia molecular no carcinoma de endométrio: uma revisão / Molecular biology in endometrial carcinoma: a review

Este artigo objetivou oferecer uma visão atual do papel dos marcadores gênicos no carcinoma de endométrio. Os principais genes descritos são o TP53, o Bcl-2, o c-erbB2 e o p16. Nos últimos anos, com a ampliação do conhecimento na área de biologia molecular, tem sido sugerido que os marcadores biológicos possam ser tão ou mais importantes do que os fatores prognósticos convencionais.

The main of this study is offer the present situation of genic markers in endometrial carcinoma. The principal genes have been described are TP53, Bcl-2, c-erbB2 and p16. In the last few years, thanks to improvements in molecular biology, some biological markers have been suggested to be as important as or more important than conventional prognostic factors.

Expression and significance of p15, p16, p21 in Uygur patients with psoriasis in Xinjiang / 中国医师杂志

Objective To investigate the expressions of p15,p16,and p21 in skin of uygur patients with psoriasis and its significance in the development of psoriasis.Methods The expressions of p15,p16,and p21 were studied with immunohistochemical method in the Xinjiang Uygur psoriatic and normal Uygur skins.Results The positive expression rate of p16 gene was 12.5％ in skin lesions of patients with psoriasis Uygur,and 66.67％ in the normal group.The positive expressions of p15,and p21 genes in skin lesions of patients with psoriasis and healthy Uygur population were higher.Conclusions There is a significant correlation between the development of uygur psoriasis vulgaris and abnormal expression of p16.

Methylation status of p16 gene and expressions of related genes in keloid tissue and cultured keloid fibroblasts / 中华皮肤科杂志

Objective To explore the role of p16 gene methylation in fibroblasts in the occurrence and development of keloid.Methods Skin tissue specimens were resected from the lesions of patients with keloid and normal skin of healthy human controls.Fibroblasts were isolated from these tissue specimens and subjected a primary culture.An immunohistochemical analysis was performed to measure the expression of p16 protein in tissue specimens,real-time fluorescence-based quantitative PCR to determine the mRNA expression level (expressed as 2-△△Ct) of p 16 and DNA methyltransferases (DNMTs) in fibmblasts,and bisulfite sequencing PCR (BSP) to estimate the methylation status of p16 gene in the tissue specimens and primary fibroblasts.Results The keloid fibroblasts (KFbs) showed significandy lower mRNA expression of p16 gene (0.64 ± 0.18 vs.1.92 ± 0.23,t =10.54,P＜ 0.05),but significantly higher mRNA expressions of 3 DNMTs (DNMT1:2.58 ± 0.23 vs.1.13 ± 0.21,t =11.22,P ＜ 0.05; DNMT3A:4.87 ± 0.46 vs.2.38 ± 0.32,t =10.81,P＜ 0.05; DNMT3B:1.57 ± 0.12 vs.0.57 ± 0.16,t =12.45,P＜ 0.05) compared with the normal fibmblasts (NFbs).The DNA methylation rate in the p16 gene promoter region was significantly increased in keloid tissue (1.81％ ± 0.46％) and KFbs (3.15％ ± 0.94％) compared with normal skin tissue (0.90％ ± 0.35％,F =14.23,P＜ 0.01) and NFbs (0.17％ ± 0.29％,F=37.62,P＜ 0.01).Conclusions The methylation and low expression of p16 gene in KFbs may be associated with the uncontrolled growth of keloid,and DNMTs may play a role in the pathogenesis of keloid.

Expression and clinical significance of IMP3 and p16 in cervical carcinoma / 国际肿瘤学杂志

Objective To detect the expression of insulin-like growth factor Ⅱ mRNA-binding protein 3 (IMP3) and p16 in cervical carcinoma and investigate their clinical significance.Methods Immunohistochemical Envision method was used to detect the expression of IMP3 and p16 proteins in 67 cases of carcinoma of the uterine cervix,58 cases of cervical intraepithelial neoplasia (CIN) and 15 cases of normal cervical epithelium.Results IMP3 was mainly dedected in the cytoplasm,whose positive expression rate was 85.07％ (57/67) in cervical carcinoma,12.07％ (7/58) in CIN (x2 =66.32,P ＜ 0.05) and 0 (0/15) in cervical epithelium (x2 =44.38,P ＜ 0.05).No significance variations of the expression of IMP3 were observed in cervical adenocarcinoma and squamous cell carcinoma (x2 =0.35,P ＞ 0.05).p16 was found both in nucleus and cytoplasm of cervical carcinoma,whose expression rate was 83.58％ (56/67),higher than 41.37％ (24/58) in CIN (x2 =24.85,P ＜ 0.05) and 0 (0/15) in cervical epithelium (x2 =42.61,P ＜ 0.05).Conclusion Expression of IMP3 and p16 is high in cervical carcinoma,maybe can be used as a potential biomarker of metastasis and progression.

Expression of Bmi-1 and p16 gene in transitional cell carcinoma of bladder / 中国医师进修杂志

Objective To detect the expression of Bmi-1 and p16 gene in transitional cell carcinoma of bladder(TCC) tissue and explore its clinical significance.Methods The expression of Bmi-1 and p16 gene were detected by real-time quantitative polymerase chain reaction in 61 cases of TCC tissue and 12 cases of normal bladder tissue.Results The expression of Bmi-1 gene in TCC tissue was significantly higher than that in normal bladder tissue (0.242 ± 0.129 vs.0.031 ± 0.011),and the expression of p16 gene was significantly lower than that in normal bladder tissue (0.059 ± 0.021 vs.0.165 ± 0.029),there was significant difference (P ＜ 0.05).The expression of Bmi-1 and p16 gene were highly correlated with pathological grades,clinical stages and tumor recurrence (P ＜ 0.05 or ＜ 0.01).But there were not correlated with age and gender (P ＞ 0.05).There was a negative correlation between the expression of Bmi-1 gene and p16 gene in TCC tissue(rs =-0.714,P＜ 0.05).Conclusions Bmi-1 gene high expression and p16 gene low expression may be involved in the occurrence and development process of TCC.Bmi-1 may decrease the expression of p 16 gene in some ways,and then lead to the occurrence and development of TCC.

Methylation of E-cadherin, p16, RASSF1A, DAPK and MGMT in salivary gland tissues / 军事医学

Objective To investigate the methylation status of E-cadherin(E-cad), p16, RASSF1A, DAPK and MGMT in histologically normal salivary gland tissues and provide reference for determination of the methylation status of salivary gland tumors.Methods Methylation of E-cad, p16, RASSF1A,DAPK and MGMT was analyzed using methylation-specific polymerase chain reaction ( MSP) .The results were compared with the methylation status of these genes in salivary adenoid cystic carcinoma ( ACC) tumor tissues in our previous studies and the association between promoter methylation of E-cad, p16, RASSF1A, DAPK, and MGMT on one hand and the patients′gender, age, smoking and types of gland on the other hand was also analyzed .Results Promoter methylation was detected in 8 of the 60 (13%) salivary glands, E-cad in 4(7%), p16 in 2(4%), RASSF1A in 2(4%), DAPK in 2 (4%), and MGMT in 1(2%).Compared with our previous results, there was a significantly lower methylation ratio in promoter methylation of E-cad(P<0.01), p16 (P<0.01), RASSF1A (P<0.01),and DAPK (P<0.01) in salivary gland tissues than in ACC tumor tissues.Conclusion Promoter methylation of E-cad, p16 and RASSF1A is a rare event in histologically normal salivary gland tissues .

Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16INK4a Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma

BACKGROUND: Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. METHODS: We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. RESULTS: All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. CONCLUSIONS: Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.

Disappearance of Serum Methylated p16 Indicates Longer Survival in Patients with Gastric Cancer

PURPOSE: The aim of this study was to assess clinical correlations with postoperative alteration of p16 DNA methylation, and to clarify whether postoperative changes in the serum DNA methylation status of p16 could be used as a reliable prognostic factor for gastric cancer. MATERIALS AND METHODS: Fifty-three consecutive gastric adenocarcinoma patients who underwent gastric resection (Chung-Ang University Hospital, Seoul, Korea) were included. DNA methylation of p16 was evaluated by methylation-specific polymerase chain reaction using serum DNA preoperatively and at the 10th postoperative day. The correlation between changes in methylation status and patients' prognosis was analyzed. RESULTS: p16 was methylated in 79.2% of preoperative serum DNA and in 54.7% of postoperative serum DNA, respectively. Methylation in p16 disappeared more frequently in patients who underwent standard D2 lymphadenectomy compared to those who underwent modified D1+ lymphadenectomy (P=0.016). Whereas methylation of preoperative serum DNA was not correlated with survival, patients with postoperative disappearance of p16 methylation showed longer survival than those without postoperative disappearance of p16 methylation in the patients who had gastric cancer with lymph node metastasis (P=0.042). CONCLUSIONS: Postoperative disappearance of p16 methylation could be an available prognostic factor for node-positive gastric cancer.

The relationship of Epstein-Barr virus infection and expression of p16 protein in classic Hodgkin's lymphoma / 中国医师杂志

Objective To study the relationship between EBV infection of classic Hodgkin's lyphoma and expression of p16 protein.Methods EBER-1 and p16 protein expression in 80 cases of CHL were studied with EBER-1 oligonucleotide probe and immunohistochemistry respectively.Results 80 cases of CHL were enrolled in this study,including male 52 cases,28 cases of female,male to female ratio of 1.86 ∶ 1.The positive rate of EBER-1 in female was 39.29％ and in male was 63.46％,which have statistically significant difference (x2 =4.298,P =0.038).The positive rate of EBER-1 in children and the older was significantly higher than that in adult (x2 =20.13,P =0.000).EBER-1 positive expression located in the R-S nuclei which positive expression rate was 55.00％,including mixed cell type (MC) 71.79％,lymphocyte depletion type (LD) 42.85％.lymphocyte predominance (LP) 47.06％ and nodular sclerosis type (NS) 29.41％.MG type was significantly higher than NS ( x2 =8.787,P =0.003 ) ; p16 was noted in thc nucleus and cytoplasm.The total positive expression rate was 45％,and subtype positive rates were 47.05％ (LP),48.71％ ( MC),35.29％ (NS) and 42.85％ (LD).There was a negative correlation between p16 protein and EBER-1 ( r =-0.242,P ＜ 0.05 ).Conclusions CHL may be related to EBV latent infection and it can be considered as potential markers to identify HRS cells in diagnosis.

Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of Relevant Literature on Korean Women

Primary endometrial squamous cell carcinoma (PESCC) is an extremely rare tumor with unclear pathogenesis. A 54-year-old postmenopausal woman presented with a 6-month history of vaginal bleeding. The patient was provisionally diagnosed with uterine submucosal leiomyoma. This was followed by total hysterectomy with a bilateral salpingo-oophorectomy under the laparoscopic guidance. Histopathologically, the tumor was PESCC which was accompanied by a lack of the tumor in the uterine cervix. The tumor showed positive immunoreactivity for p16INK4a. But there was no evidence of human papillomavirus (HPV) on in situ hybridization and HPV DNA chip analysis. We also present a review of the relevant literature on Korean women.