Association of p53/p21 expression with cigarette smoking and prognosis in esophageal squamous cell carcinoma patients

【Abstract】factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P【0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P【0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.

Prognostic Value of P-gp and p27 in Patients with Esophageal Squamous Cell Carcinoma

Objective： To evaluate the prognostic value of P-gp and p27 expression in patients with esophageal squamous cell carcinoma （ESC）. Methods： The expressions of P-gp and p27 were detected by immunohistochemistry in 104 cases of ESC, and the clinicopathological characteristics were analyzed as well. Results： The positive rate of P-gp expression in 104 cases of ESCs was 32.7%. The positive rate of P-gp expression in the group that survived over 3 years （17.5%） was significantly lower than that in the group died within 3 years （53.3%） （x^2=14.227, P〈0.001）. The positive rate of p27 expression in 104 cases of ESCs was 67.3%. The positive rate of p27 expression in the group that survived over 3 years （75.8%） was significantly higher than that in the group died within 3 years （56.5%） （x^2=4.361, P〈0.05）. The patients with poorer differentiation whole wall invasion, lymph node metastasis and more advanced TNM stage had a shorter survival than did those with better differentiation, more superficial invasion, no lymph node involvement and earlier TNM stage; and it was statistically significant （P〈0.05）. However, tumor size, macropathologic type, age and gender had no prognostic impact on ESC patients （P〉0.05）. Conclusion： P-gp and p27 expression levels had a clinical prognostic significance in ESC. It could provide a reference basis for selecting the chemotherapy projection. The tumor differentiation degree, depth of invasion, lymph node involvement and TNM stages all were correlated to ESC patients＇ survival.

Expression and clinical significance of S100A2 and p63 in esophageal carcinoma

AIM： TO investigate the expression and clinical significance of S100A2 mRNA and protein, p63 protein in esophageal squamous cell carcinoma （ESCC） and their roles in carcinogenesis and progression of esophageal carcinoma （EC）. METHODS： Immunohistochemical staining （S-P method） for S100A2 and p63 protein were performed in 40 samples of ESCC and 40 samples of normal esophageal mucosa. In situ hybridization （ISH） was used to detect the expression of S100A2 mRNA. RESULTS： Expression of S100A2 mRNA in ESCC was positive in 77.5% of samples, which was lower than that in normal mucosa （100%） by ISH （P = 0.002）. The expression level of S100A2 mRNA was closely related to differentiation and and node-metastasis （P = 0.012, P = 0.008）. Expression of $100A2 protein was positive in 72.5% of ESCC samples and expression of p63 protein was positive in 37.5% of ESCC samples, and was lower than that in normal mucosa （100%） （P = 0.000）. The expression of S100A2 protein was correlated with the differentiation and node-metastasis （P = 0.007, P = 0.001）, but no relationship was observed between the expression of p63 protein and clinical pathological manifestations. S100A2 protein was positively correlated with the expression of S100A2 mRNA, and negatively associated with the expression of p63 protein （P = 0.000, P = 0.002）. CONCLUSION： S100A2 and p63 protein both play important roles in the carcinogenesis of ESCC. An investigation into the combined expression of S100A2 and p63 may be helpful in early diagnosis and in evaluating the prognosis of ESCC.

Relationship between COX-2 and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma

AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemoor radiotherapy prior to surgical resection.Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7±61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P<0.01). In contrast, the protein level of p27 was signifi cantly lower in ESCC than in normal squamous epithelium (182.0 ±69.0 vs 266.4±28.0, P<0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0±42.3 vs 83.0 ± 66.5, P<0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8±31.7 vs 98.4± 84.8, 32.0 ± 19.0 vs 54.1 ±53.7,206.2±61.5 vs 123.5±68.3, respectively, all P<0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r=0.270, 0.233 and-0.311, respectively, all P<0.05).CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.

Expressions and the clinical significances of p53, p57(Kip2) and CD68 in esophageal squamous cell carcinoma

Objective： The aim of our study was to investigate the expression of p53, p57（Kip2） and CD68 in esophageal squamous coil carcinoma （ESCC） and their correlation with the biological behavior of ESCC. Methods： The protein expres- sions of p53, p57（Kip2） and CD68 were detected in 51 cases of ESCC with S-P immunohistochemical method. Results： The total positive rate of those proteins was p53 64.71%, CD68 58.82% and p57（Kip2） 45.09% respectively in ESCC. The positive expression rate of p57（Kip2） was significantly lower in the positive p53 of ESCC than in the negative p53 （P 〈 0.05）. The positive expression rate of p57（Kip2） was significantly lower in the positive CD68 of esophageal squamous cell carcinoma than in the negative （P 〈 0.05）. The positive expression of p53 and CD68 were related to differentiate and TNM of ESCC, but p57（Kip2） was not related to TNM （P 〉 0.05）. Conclusion： There are significant negative correlations between p57（Kip2） and p53, CD68 protein expression and related to biological behavior. Multy predictors are better guide to patients than single predictor.

Expression of p73, ER and PR in esophageal carcinoma and precancerous lesions

Objective： To test the expression of mutant p73, p53, ER and PR proteins in the esophageal normal mucosa, hyperplasia, dysplasia and squamous cell carcinoma, and research the clinically pathological significance and the correlation, for the early diagnosis, prognostic measure and therapy in clinic. Methods： With Immunohistochemistry, it was examined to show these tumor markers＇ expression in different epithelial lesions of 40 esophageal squamous cell carcinomas, 14 dysplasias, 14 hyperplasias and 14 normal mucosas. Results： The expression of p73 was 55%, 21%, 0% and 0% in the esophageal carcinoma, dysplasia, hyperplasia and normal mucosa, respectively. The significant difference in expression of p73 （P〈0.001） was observed between the esophageal normal mucosia, hyperplasia, dysplasia and esophageal squamous cell carcinoma with Fisher＇s exact test. Difference in expression of p73 （P〈0.05） was observed between the esophageal squamous cell carcinoma and dysplasia with X^2 test. The expression of p73 showed non-correlation with the patient＇s age, sex, tumor＇s grade, lymph-node metastasis and invasive depth （P〉0.05）; Similarly, the expression of mutant p53 was 67.5%, 35.7%, 7% and 0%, respectively; In like manner, the expression of ER was 55%, 21.4%, 14.2% and 0%, respectively; The expression of PR was 57.5%,14.28%, 0% and 0%, respectively. The significant difference in expression of PR （P〈0.001） was observed with Fisher＇s exact test. Difference in expression of PR （P〈0.05） was observed between the esophageal squamous cell carcinoma and dysplasia with x2 test. The expression of PR （P〈0.05） was correlated with lymph-node metastasis, and showed non-correlation with the patient＇s age, sex, tumor＇s grade, and invasive depth （P〉0.05）. Moreover, over-expression of mutant p53 and p73 showed significant correlation with ER and PR protein＇s positive expression （P〈0.05）. Conclusion： P73 protein may become a new tumor＇s marker to diagnose esophageal squarnous celt carcinoma. Because the expression of p73 protein was closely correlated with ER and PR, they could be simultaneously examined to help to early diagnose, prognosticate and cure esophageal carcinoma.

食管癌组织P110α和pAKT蛋白的表达及其临床意义

目的:探讨食管癌组织中P110α、pAKT的表达与食管癌临床病理特征之间的关系。方法:收集2010年5月至2011年5月苏州大学附属第一医院76例患者的食管癌组织标本,25例正常对照食管黏膜组织标本来自解放军第101医院病理科。免疫组织化学SP法检测食管癌及正常食管黏膜组织中P110α及pAKT的表达水平。结果:76例食管癌组织pAKT表达阳性率为72.4%(55/76)、P110α表达阳性率为57.9%(44/76),均明显高于对照组(PpAKT=0.001,PP110α=0.025)。食管癌组织中pAKT、P110α的高表达与食管癌淋巴结转移相关(PpAKT=0.017,PP110α=0.009),与其他临床病理特征无关。食管癌组织中pAKT与P110α双阳性率为52.6%(40/76),两者的表达呈正相关(r=0.486,P=0.001)。结论:食管癌组织中P110α、pAKT表达与淋巴结转移相关,有可能成为临床检测食管癌淋巴结转移的生物指标。

mTOR和p-p70S6K在食管鳞癌组织中蛋白表达的相关性及其临床意义

目的:探讨哺乳动物雷帕霉素靶蛋白(mTOR)及其下游关键因子p-p70S6K的表达与食管鳞癌发生、发展及浸润、转移的关系.方法:35例食管癌手术切除标本取自河南省安阳市肿瘤医院.应用免疫组织化学SP法检测35例食管鳞癌组织,15例癌旁不典型增生组织及15例正常食管黏膜组织中mTOR及p-p70S6K蛋白的表达.结果:食管鳞癌组织中mTOR蛋白表达与肿瘤TNM分期密切相关(χ2=9.121,P<0.05);在食管鳞癌癌变过程中,mTOR蛋白在正常黏膜组织、癌旁不典型增生组织及癌组织中的表达率依次增高,分别为20%(3/15)、46.7%(7/15)、62.9%(22/35),组间比较有明显差异(χ2=7.767,P<0.05).p-p70S6K蛋白表达与肿瘤的淋巴结转移及TNM分期密切相关(χ2=5.846,4.523;均P<0.05),其在正常黏膜组织、癌旁不典型增生组织及癌组织中的表达率依次增高,分别为33.3%(5/15)、73.3%(11/15)、74.3%(26/35),组间比较有明显差异(χ2=8.350,P<0.05),mTOR及p-p70S6K的表达呈正相关关系(γp=0.359,P=0.034).结论:mTOR及p-p70S6K蛋白在食管鳞癌组织中表达显著升高,且二者与食管鳞癌的生物学行为关系密切.提示二者高表达与食管鳞癌的发生、发展有关,可作为食管鳞癌早期诊断和判断预后的辅助指标.

p63、P-gp、GST-π及Topo-Ⅱ在食管鳞癌组织中的表达

目的:观察比较p63、P-糖蛋白(P-gp)、谷甘胱肽-S-转移酶π(GST-π)、DNA拓扑异构酶(Topo-Ⅱ)在食管癌中的表达情况,并探讨其关系和临床意义。方法:采用免疫组化方法对168例食管鳞癌组织中p63、P-gp、GST-π、Topo-Ⅱ蛋白进行检测,分析其与病理特征的关系及协同表达的意义。结果:p63、P-gp、GST-π、Topo-Ⅱ蛋白在食管鳞癌中的阳性表达率分别为81.0%、57.1%、71.4%、78.6%。p63的表达与肿瘤的临床分期、浸润深度、淋巴结转移相关(P<0.05),P-gp和TopoⅡ的表达与淋巴转移有关(P<0.05),GST-π的表达与肿瘤分化程度、淋巴结转移有关(P<0.05)。p63的阳性表达与P-gp、GST-π呈正相关(r=0.193、0.197,P<0.05),P-gp与GST-π表达呈正相关(r=0.224,P<0.05),P-gp与TopoⅡ表达呈负相关(r=-0.218,P<0.05)。结论:p63、P-gp、GST-π及Topo-Ⅱ均与食管癌发生发展有关,对肿瘤化疗方案的选择和预后判断有重要的临床意义。

食管鳞癌中CD44H、P-选择素和血管内皮生长因子的表达与淋巴结转移的关系

目的探讨CD44H、P-选择素(P-selectin)和血管内皮生长因子(VEGF)的表达与食管鳞癌淋巴结转移的关系。方法采用免疫组织化学SP法检测60例食管鳞癌组织中CD44H、P-selectin和VEGF的表达。结果淋巴结转移组CD44H、P-selectin和VEGF的表达增强,与无淋巴结转移组的表达差异有显著性意义(P<0.05),P-selectin和VEGF在淋巴结转移组的表达呈正相关(P<0.05)。结论CD44H、P-selectin和VEGF的表达与食管鳞癌淋巴结的转移密切相关,P-selectin和VEGF存在协同关系,可作为评估食管鳞癌预后的生物学标志。

P-糖蛋白在食管鳞癌组织中表达及临床意义

目的:研究食管鳞癌组织中P-糖蛋白(P-glycoprotein,P-gp)的表达,探讨其与食管鳞癌临床病理因素的关系。方法:应用免疫组织化学方法检测63例食管癌标本的P-gp的表达。结果:在所检测的63例食管癌标本中,阳性者41例65.08%。P-gp表达与患者性别、年龄、血型、肿瘤浸润的深度等无相关性,与肿瘤分化的程度、淋巴结转移有相关性。结论:P-gp在食管癌的多药耐药中可能起一定作用,检测P-gp对食管癌的临床化疗药物选择可能有一定指导作用;P-gp的表达可在一定程度上反映食管鳞癌的分化程度及淋巴结转移情况。

食管鳞癌组织中P-selectin的表达与淋巴结转移的关系

目的 探讨P selectin在食管鳞癌中的表达水平及其与食管癌病理分级和淋巴结转移的关系。方法 应用原位杂交及免疫组化SP技术研究了P selectinmRNA及蛋白在有转移的和无转移的食管鳞癌中的表达。结果 癌组织中P selectinmRNA及蛋白的阳性率在有转移的食管鳞癌中的表达分别为 76.2 % ( 16/2 1)和 85 .7% ( 18/2 1) ,在无转移的食管鳞癌中的表达分别为 48.5 % ( 16/3 3 )和5 4.5 % ( 18/3 3 )。它们的表达与浸润深度和淋巴结转移呈正相关 (P <0 .0 5 )。P selectinmRNA与P selectin蛋白的表达呈明显负相关(r =0 .0 0 5 )。结论 P

P-P38和uPA蛋白在食管鳞癌中的表达及意义

目的探讨P-P38蛋白和uPA蛋白在食管鳞癌组织中的表达及临床意义。方法采用微波EliVi-sionTM免疫组织化学法检测60例食管鳞癌组织中P-P38蛋白和UPA蛋白的表达情况,并与40例正常食管黏膜组织进行比较。结果食管鳞癌组织中P-P38和uPA分别表达定位于细胞核和细胞浆,其表达明显高于正常食管黏膜组织(P<0.05)。两者的表达与肌层浸润程度、淋巴结转移、临床分期及病理分期有关(P<0.05);两者之间表达呈正相关(P<0.05)。结论 P-P38和uPA在食管鳞癌呈高表达,且在食管鳞癌的发生、发展和转移过程中起一定的作用。

P-糖蛋白在食管癌的表达及其意义

目的 观察Ｐ－糖蛋白（Ｐ－ｇｐ）在食管癌的表达并探讨其临床生物学意义。方法 应用免疫组织化学方法检测６７ 例未进行化疗的食管癌和４４ 例食管癌周正常组织中Ｐ－ｇｐ 的表达。结果 Ｐ－ｇｐ 在４４ 例正常食管粘膜上皮中的表达率是８６．４％ ，在６７ 例食管癌组织中的表达为５６．７％ （Ｐ＜ ０．０１）。Ｐ－ｇｐ 在食管癌的表达与组织分化程度有关。随着癌组织分化程度的下降及出现淋巴结转移时，Ｐ－ｇｐ 表达率也下降，耐药性减弱。结论 检测Ｐ－ｇｐ 的表达对食管癌治疗方案的选择有指导意义。

P-糖蛋白在食管贲门癌中的表达及意义

目的探讨P-糖蛋白(P-gp)在食管贲门癌中的表达及意义。方法应用免疫组化方法检测P-gp在69例食管鳞癌和64例贲门腺癌及相应癌旁正常组织中的表达。分析P-gp的表达与肿瘤分化程度、浸润深度及淋巴结转移之间的关系。结果P-gp在69例食管癌中仅1例表达阳性,表达率为1.45%,P-gp在贲门癌中的表达率为57.8%,二者比较差异有统计学意义,并且P-gp在贲门癌中的表达高于相应癌旁正常组织(P<0.05)。P-gp的表达与贲门癌的分化程度有关(P<0.05),而与癌的浸润深度、淋巴结转移无关(P>0.05).结论P-gp在食管癌的多药耐药中所起作用甚微,食管癌的多药耐药可能与其他耐药蛋白的表达有关;而贲门癌的多药耐药则与P-gp的表达有关;P-gp的表达可在一定程度上反映肿瘤的分化程度,但并不能反映肿瘤的浸润、转移等生物学特征。

P-Akt蛋白的表达与梅州地区客家人食管鳞癌的关系

目的探讨p-Akt蛋白的表达与梅州地区客家人食管鳞癌的关系。方法应用免疫组织化学SABC法检测食管鳞癌和食管良性肿瘤组织中p-Akt蛋白的表达。结果 p-Akt蛋白全部着色在细胞浆,食管鳞癌组织中的阳性表达率为86.9%,高于食管良性肿瘤组织的6.2%,差异有统计学意义(P<0.001)。结论 p-Akt蛋白的过量表达与梅州地区客家人食管鳞癌的发生有关。

食管粘膜下鳞癌生物学特性及P^(53)蛋白表达的意义

目的 研究食管粘膜下鳞癌的生物学特性。方法 通过随访及SP免疫组化技术P53 蛋白在 3 0例食管粘膜下鳞癌的表达 ,研究其生物学特性。结果 3 0例食管粘膜下鳞癌的P53 蛋白阳性表达率为 66.7% ,经病理证实术时淋巴结的转移率为 60 % ,术后各种转移率为 47.8% ,其中伴肺转移 4例 ,单纯肺转移 1例 ,其 1、2、3、4年生存率分别为 10 0 %、70 .0 %、3 1.3 %和 11.1%。结论 食管粘膜下鳞癌术时及术后转移率较高 ,术后肺转移率较高 ,P53 蛋白阳性表达率高 ,予后差。鳞化伴异型增生的食管腺上皮细胞的阳性表达提示食管粘膜下鳞癌可能发生于食管腺。

食管鳞癌中P-P38和VEGF蛋白的表达及意义

目的:探讨P-P38蛋白和VEGF蛋白在食管鳞癌组织中可能的作用。方法:采用微波EliVisionTM免疫组织化学法检测60例食管鳞癌组织中P-P38蛋白和VEGF蛋白的表达情况,并与40例正常食管粘膜组织进行比较。结果:食管鳞癌组织中P-P38和VEGF分别表达定位于细胞核和细胞浆,其表达明显高于正常食管粘膜组织(P<0.05)。两者的表达与淋巴结转移、分化程度及病理分期有关(P<0.05);两者之间表达呈正相关(P<0.05)。结论:P-P38和VEGF在食管鳞癌呈高表达,且在食管鳞癌的发生、发展和转移过程中起到一定的作用。