乳腺浸润性癌PS2蛋白的表达及其与预后的关系

目的探讨ＰＳ２蛋白在乳腺浸润性癌中的表达及其与预后的关系。方法应用ＬＳＡＢ免疫组化法检测ＰＳ２蛋白在８６例乳腺浸润性癌中的表达。结果ＰＳ２蛋白的表达率为６６．２７％（５７／８６）。在下列一些情况中，ＰＳ２蛋白的表达率有区别：（１）８６例中，５年以上组８０．５５％（２９／３６），５年以下组５６．００％（２８／５０），差异有显著性意义（Ｐ＜０．０２５）；（２）未停经组６２例，５年以上组８６．２０（２５／２９），５年以下组５４．５４％（１８／３３），差异有显著性意义（Ｐ＜０．００５），已停经组２４例，５年以上组４／７例，５年以下组５８．８０％（１０／１７），差异无显著性意义；（３）腋窝淋巴结转移６２例，５年以上组８２．３５％（１４／１７），５年以下组５５．５５％（２５／４５），差异有显著性意义（Ｐ＜０．０５）；腋窝淋巴结阴性２４例，５年以上组７８．９４％（１５／１９），５年以内组３／５例，差异无显著性意义。结论本研究表明，ＰＳ２蛋白的阳性表达与５年生存期正相关，ＰＳ２阳性的表达可以作为乳腺癌的一项预后指标；ＰＳ２蛋白表达对未停经患者的内分泌治疗具有一定的指导意义；腋窝淋巴结阳性患者ＰＳ２蛋白表达与较好的预后相关。     

喉鳞状细胞癌中MTA2的表达及预后分析

目的探讨转移相关蛋白2(metastasis-associated protein 2,MTA2)在喉鳞状细胞癌组织中的表达,分析其与临床病理特征和患者预后的关系。方法采用免疫组化SP法检测120例喉石蜡包埋组织中MTA2蛋白的表达,采用Western blot法检测喉新鲜组织中MTA2蛋白的表达量,利用Kaplan-Meier法绘制总生存期曲线,Log-rank方法分析两组生存曲线差异,Cox比例风险回归模型筛选喉鳞状细胞癌患者的预后影响因素。结果MTA2在正常喉组织、高级别鳞状上皮内病变和喉鳞状细胞癌组织中的阳性率分别为6.67%、43.33%和73.33%,差异有统计学意义(χ^2=36.11,P<0.001),MTA2表达与喉鳞状细胞癌组织学分级、临床分期及淋巴结转移显著相关(P均<0.05);在正常喉组织、高级别鳞状上皮内病变及喉鳞状细胞癌组织中MTA2的相对表达量分别是0.98±0.07、1.30±0.07和1.46±0.11,差异有统计学意义(F=121.194,P<0.001);Kaplan-Meier生存分析提示MTA2表达与喉鳞状细胞癌患者的生存期显著相关(P<0.05);多因素回归分析表明MTA2蛋白表达、临床分期及淋巴结转移是喉鳞状细胞癌患者有效的独立预后指标(P均<0.05)。结论MTA2过表达在喉鳞状细胞癌发生、进展过程中发挥重要作用,可作为喉鳞状细胞癌独立的预后因素,MTA2有望成为指导喉鳞状细胞癌治疗和判断患者预后的新分子学标志物。     

喉鳞状细胞癌中ZNF750的表达及与预后的关系

目的探讨ZNF750的表达与喉鳞状细胞癌临床病理特征及预后的相关性。方法收集115例喉鳞状细胞癌及56例对应癌旁正常喉组织,另收集6对新鲜喉鳞状细胞癌组织及配对癌旁正常喉组织。采用Western blot法和免疫组化法检测喉鳞状细胞癌组织及癌旁正常喉组织中ZNF750蛋白的表达;采用Kaplan-Meier生存曲线和Cox比例风险回归模型分析ZNF750蛋白表达与喉鳞状细胞癌患者预后的关系。结果 ZNF750在喉鳞状细胞癌组织中的表达明显低于癌旁正常喉组织(P0.05),ZNF750蛋白表达与喉鳞状细胞癌的淋巴结转移、TNM分期密切相关(P0.05),同时喉鳞状细胞癌患者中ZNF750蛋白高表达组的总生存率均高于ZNF750低表达组(P0.05)。结论 ZNF750在喉鳞状细胞癌组织中的表达与淋巴结转移、TNM分期有关,其有望成为预测喉鳞状细胞癌患者预后的指标。     

SLP-2在胃癌组织中的表达及其预后意义

 目的：探讨红细胞膜整合蛋白SLP-2（stomatin-like protein 2）在胃癌中的表达及其与临床病理学指标及预后的关系。方法：选取中山大学肿瘤防治中心病理科有完整临床资料的胃癌手术标本190例,应用免疫组织化学方法检测胃癌中SLP-2蛋白的表达,并分析其与临床病理特征及预后的关系。结果：（1）胃癌组织中SLP-2蛋白表达的阳性率为63.2%（120/190）。SLP-2表达与胃癌浸润深度、TNM分期及淋巴结转移有关（P<0.05）,而与患者性别、年龄、肿瘤分化程度、肿瘤直径和远处转移均无关（P>0.05）;（2）Kaplan-Meier 生存曲线分析结果显示：SLP-2阳性表达患者的累积生存率明显低于阴性表达患者（P<0.01）;（3）单因素分析结果显示：SLP-2 的表达、淋巴结转移、肿瘤分化程度、肿瘤直径、TNM分期、浸润深度及远处转移均影响胃癌预后;多因素分析表明,只有肿瘤直径和TNM分期是独立的预后指标。结论：（1）SLP-2在胃腺癌组织中高表达,可能参与胃腺癌的发生发展和转移;（2）SLP-2在一定程度上影响胃癌的预后,其过度表达提示胃癌预后差。     

淋巴结转移密度与乳腺浸润性导管癌预后的关系

目的探讨淋巴结转移密度与手术治疗乳腺浸润性导管癌患者预后的关系。方法回顾性分析113例乳腺浸润性导管癌的临床资料,按淋巴结转移密度分为ND40组、ND=0组和ND≤40组,采用Kaplan-Meier法和Cox比例风险模型,比较临床病理特征及淋巴结转移密度评价手术治疗乳腺浸润性导管癌患者5年无瘤生存率和总生存率的价值。结果 ND40组、ND=0组和ND≤40组5年无瘤生存率及总生存率,差异有统计学意义(P均0.05)。在Ⅲ期乳腺癌患者中,淋巴结转移密度提供良好的分层意义,ND40组Ⅲ期乳腺癌与Ⅳ期乳腺癌预后无差异(P=0.453)。单因素分析显示,脉管癌栓、淋巴结转移密度、TNM分期、雌、孕激素受体状态及p N分期均与患者的5年无瘤生存率和总生存率有关(P均0.05)。多因素分析显示,组织学分级及淋巴结转移密度是影响患者5年无瘤生存率的独立因素(P均0.05);淋巴结转移密度是影响患者5年总生存率的独立因素(P0.05)。结论淋巴结转移密度是手术治疗乳腺浸润性导管癌患者预后的独立因素,提示其可作为乳腺癌预后的参考标准,ND40组提示预后不良。     

乳腺浸润性导管癌中COX-2、VEGF-C和VEGFR-3的表达及其意义

目的本研究通过检测乳腺癌组织中COX-2、VEGF-C和VEGFR-3的表达及其意义,探讨其在乳腺癌淋巴管转移中的发生发展机制。方法采用免疫组化SP法检测60例乳腺癌组织标本(有腋窝淋巴结转移组27例,无腋窝淋巴结转移组33例)中COX-2、VEGF-C和VEGFR-3的表达。结果乳腺癌组织中COX-2、VEGF-C和VEGFR-3的阳性表达明显高于正常乳腺组织,差异有统计学意义(P0.01)。淋巴结转移组COX-2和VEGF-C阳性表达明显高于无淋巴结转移组,差异有统计学意义(P0.01、P0.05)。淋巴结转移组VEGFR-3阳性脉管数明显高于无淋巴结转移组,差异有统计学意义(P0.01)。结论乳腺癌组织中COX-2、VEGF-C和VEGFR-3的阳性表达明显高于正常乳腺组织;COX-2、VEGF-C和VEGFR-3的阳性表达与乳腺癌淋巴道转移密切相关。     

P53和Ki-67在喉鳞状细胞癌中的表达及与短期预后的关系

目的:探讨P53和Ki-67在喉鳞状细胞癌(laryngeal squamous cell carcinoma,LSCC)中的表达情况及临床病理参数和短期预后相关分析.方法:选择手术切除LSCC标本35例,肿瘤分期均为T3~4N0M0.采用SP法染色进行P53和Ki-67免疫组织化学标记,结合临床病理参数和2年随访结果及无病生存情况进行统计学分析.结果:LSCC标本P53阳性率为60.00%;2年复发率P53阳性患者76.19%高于P53阴性28.59%,差异具有统计学意义(P=0.013).年龄大小、是否抽烟、增殖指数高低及肿瘤不同分级方面,患者2年内复发率差异均无统计学意义.T3~4N0M0分期患者的短期预后与P53表达高低相关.结论:P53的过表达对晚期LSCC短期预后评估具有一定的临床意义,可考虑作为晚期LSCC分层治疗指标.     

乳腺癌组织中Survivin表达及其与预后的关系

目的 探讨Survivin在乳腺癌组织中的表达情况及预后的关系.方法 采用SP法免疫组化对50例术前未行放、化疗的乳腺癌蜡块标本及其癌旁组织进行Survivin检测,以及对10例正常乳腺组织进行Survivin检测.结果 乳腺癌组织及癌旁组织中Survivin阳性率分别是68%、4%.正常乳腺组织中无Survivin表达,三者之间的阳性率差异有显著性(P<0.05).结论 Survivin在乳腺癌组织中表达上调,提示该基因在乳腺癌发生发展中起重要作用,检测Survivin、有助于提高对乳腺癌预后判断的准确性.     

Six1和Six4在食管鳞状细胞癌组织中的表达及其与预后的关系北大核心CSCD

目的探讨Six1和Six4在食管鳞状细胞癌（简称鳞癌）组织中的表达及其与临床病理特征及预后的关系。方法应用组织芯片技术、免疫组织化学EnVision法检测Six1和Six4在292例食管鳞癌组织及其相应的癌旁正常食管上皮组织中的表达水平,分析两者表达与临床病理特征及预后之间的关系。结果在292例食管鳞癌患者中,Six1、Six4蛋白在癌组织的阳性率分别为72．9％（213／292）和56．2％（164／292）,明显高于癌旁正常组织的阳性率,分别为33．2％（97／292）和32．5％（95／292）,差异具有统计学意义（P〈0．05）。X2检验结果显示Six1蛋白表达与肿瘤大小、肿瘤浸润深度及生存状态相关,其在死亡组患者的阳性率82．3％（130／158）,明显高于生存组阳性率61．9％（83／134,P〈0．05）。Six4蛋白表达与肿瘤分化程度及肿瘤浸润深度相关,肿瘤分化程度越高、浸润深度越深其阳性率越高。单因素Log-rank分析显示性别、TNM分期、Six1蛋白表达与食管鳞癌患者的总生存率相关（P〈0．05）。Six1蛋白表达阴性组5年生存率51．9％（41／79）高于阳性组的43．7％（93／213）,差异具有统计学意义（X^2=4．079,P=0．043）,其他临床参数与预后均未显示统计学意义（P〉0．05）。多因素Cox比例风险模型分析显示,TNM分期、Six1蛋白表达水平是影响食管癌术后患者预后的独立因素（P〈0．05）。结论Six1和Six4蛋白在食管鳞癌组织中均高表达,其表达水平与食管鳞癌发生发展及预后密切相关,Six1蛋白高表达是食管鳞癌患者预后不良的因素,可作为临床预测食管鳞癌患者预后的一个重要指标。     

Mnk2蛋白水平与食管鳞癌预后的相关性

目的:检测丝裂原活化蛋白激酶相互作用激酶2(mitogen-activated protein kinase-interacting kinase-2,Mnk2)在食管鳞状细胞癌中的表达水平,并探讨其与患者生存预后的相关性。方法:收集临床食管鳞癌标本86例及癌旁正常食管组织54例,应用Western blot法和免疫组化SP法检测肿瘤组织及正常食管黏膜组织中Mnk2蛋白表达水平,并用Kaplan-Meier生存曲线和Cox比例风险回归模型的方法探究其与食管鳞癌患者预后的关系。结果:Mnk2在食管癌组织中呈高表达,并且Mnk2蛋白表达与食管鳞癌的TNM分期密切相关(P0.05),同时Mnk2蛋白高表达组的无疾病进展生存期和总生存期均少于Mnk2低表达组,多因素分析提示Mnk2是食管鳞癌的独立预后因子。结论:Mnk2在食管鳞癌组织中的表达与TNM分期有关,同时可作为预测食管鳞癌患者预后的指标。     

人宫颈鳞状细胞癌Bcl-2的表达与放射治疗敏感性的关系

目的 探讨人宫颈鳞状细胞癌放射治疗的敏感性与治疗前癌组织中Bcl-2表达的关系。方法 32例经活检病理诊断确诊的宫颈鳞状细胞癌患者，照射（40Gy）后行宫颈癌根治切除，并做组织学检查。根据放疗效果分为敏感组与耐受组。采用免疫组织化学染色方法，对其放疗前后癌组织进行Bcl-2检测并对照观察。结果 放疗后，在40．6％（13／32）病例的手术切除标本中无癌组织存留，定为敏感组；另59．4％（19／32）的病例放疗后显示仍有癌组织残留，为耐受组。放疗前活检癌组织Bcl-2的表达在敏感组和耐受组分别为15．4％（2／13）和63．2％（12／19），耐受组明显高于敏感组（P＜0．05）。结论 原发性人宫颈鳞状细胞癌Bcl-2的高表达可导致肿瘤对辐射的耐受，认为Bcl-2的表达状态可能作为预测宫颈鳞状细胞癌放疗敏感性的一项指标。     

口腔鳞状细胞癌组织中HPV感染及EGFR、Sox2蛋白表达与肿瘤预后的相关性

目的探讨口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)组织中人乳头状瘤病毒(human papiloma virus,HPV)感染及EGFR、Sox2表达与肿瘤复发的关系。方法收集OSCC组织标本85例,分别采用PCR-DNA反向点杂交及免疫组化SP法检测蜡块组织中HPV感染及EGFR、Sox2表达,收集患者病理资料并进行随访。结果 HPV在OSCC组织中的检出率为29.4%(25/85),阳性患者以非吸烟者居多,高于阴性患者(P0.001)。HPV感染与患者性别、年龄、肿瘤部位、临床分期、分级及淋巴结转移无明显相关性(P0.05);EGFR、Sox2的阳性率分别为69.4%(59/85)、71.8%(61/85);EGFR表达与肿瘤分化程度有关(P0.001);Sox2表达与肿瘤分化程度及TNM分期有关(P0.001、P0.009)。随访2年以上的OSCC患者中17例出现复发(复发组),HPV阳性患者治疗后复发率为5.9%(1/17),低于HPV阴性患者(P=0.037);EGFR、Sox2蛋白在复发组和未复发组中阳性率分别为88.2%、94.1%及64.7%、66.2%;Sox2蛋白在复发组中的阳性率明显高于未复发组(P=0.047)。结论 OSCC中存在一定比例的HPV感染及EGFR、Sox2表达;HPV阳性患者复发率低于阴性患者;EGFR表达与肿瘤分级有关;Sox2表达与肿瘤分级、TNM分期及复发相关。HPV阴性、EGFR及Sox2阳性患者治疗后应定期随诊。     

Role of HPV status and PD-L1 expression in prognosis of laryngeal squamous cell carcinoma

Purpose: Human papillomavirus (HPV) infection has been recognized as a cause of head and neck squamous cell carcinomas (HNSCC). Laryngeal squamous cell carcinoma (LSCC) is one of the most common pathologic types of HNSCC. Clinical trials show that there are differences in response to immunotherapy according to HPV status. It was reported that a high level of programmed cell death-ligand 1 (PD-L1) is correlated with better survival in HPV-positive head and neck cancer. In this study, we investigated the expression of PD-L1 in HPV-positive and HPV-negative LSCC to determine its prevalence and prognostic value. Methods: 52 cases of LSCC were collected from Tangshan Head and Neck Disease Pathology Research Base. PCR-reverse dot blot hybridization and RNAscope in situ hybridization were used to detect HPV status. PD-L1 expression was evaluated by immunohistochemistry and all cases were followed up for survival. SPSS24.0 was used for data entry and statistical analysis. Kaplan-Meier method and Log-rank time series analysis were used for single factor analysis. Multivariate analysis was performed using Cox proportional hazard regression model, and HR and 95% CI were calculated. Results: Of the 52 LSCC patients, 32.7% (17/52) were HPV-positive by RNAscope in situ hybridization, and 51.9% (27/52) of patients were positive for PD-L1 expression by immunohistochemistry. Regression analysis showed that with a median follow-up period of 69 months, smoking and late stage were associated with poor overall survival (OS), whereas HPV positivity and PD-L1 expression showed a better overall survival outcome. Conclusion: Smoking status, tumor stage, HPV status, and PD-L1 expression in tumor cells may represent useful prognostic biomarkers in patients with LSCC.     

Nuclear PKM2 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors worldwide, with a high malignant degree and poor prognosis. The present study aims to investigate the relationship between pyruvate kinase M2 (PKM2) expression and the prognosis of patients with ESCC. The expression of PKM2 in 86 cases of esophageal carcinoma tissues was tested using immunohistochemistry. The relationship between PKM2 expression and clinical pathological parameters, and their effects on the prognosis of patients with ESCC were analyzed. The expression levels of PKM2 in both cytoplasm and nucleus of ESCC tissues were significantly higher than those in paracancerous tissues (P = 6.73 × 10⁻⁹ and 4.32 × 10⁻⁶, respectively). The Kaplan–Meier analysis showed that nuclear PKM2 expression was closely related to the survival of patients with ESCC (P = 0.005). Patients with high PKM2 expression in the nucleus had significantly shorter survival times than those with low PKM2 expression in the nucleus (hazard ratio for death, 2.358; 95% confidence interval, 1.156–4.812; P = 0.018). No other significant difference was found between PMK2 expression and clinico-pathological features of ESCC patients (all P > 0.05). In conclusion, high PKM2 expression in the nucleus is essential in the pathogenic process of ESCC and may be used to predict the prognosis of patients with ESCC.     

Mammalian target of rapamycin expression and laryngeal squamous cell carcinoma prognosis: novel preliminary evidence

Marioni G, Staffieri A, Giacomelli L, Lionello M, Guzzardo V, Busnardo A & Blandamura S
(2011) Histopathology  58, 1148–1156
Mammalian target of rapamycin expression and laryngeal squamous cell carcinoma prognosis: novel preliminary evidence Aims: The mammalian target of rapamycin (mTOR) has a key role in regulating cancer cell proliferation, apoptosis, cell migration, and angiogenesis. The aim of this study was to assess the relationships between mTOR and clinicopathological and prognostic parameters in laryngeal squamous cell carcinoma (SCC). Methods and results: Mammalian target of rapamycin expression was determined in 103 consecutive operable laryngeal SCCs. Among the mTOR‐positive cases, the locoregional recurrence rate was higher (P = 0.048) and the disease‐free survival (DFS) rate was shorter (P = 0.031) in patients with mTOR expression >50.7%. In the N₀ subgroup, the disease recurrence rate was higher (P = 0.034) and the DFS was shorter (P = 0.009) in patients with mTOR expression >50.7%. In mTOR‐positive patients, multivariate analysis showed that N stage (P = 0.0001) and mTOR status (P = 0.042) were independent indicators of a poor prognosis. Conclusions: mTOR appeared to be a significant predictor of DFS in univariate and multivariate models. mTOR expression in laryngeal SCC may be useful for the detection of patients at higher risk for recurrence, and N₀ patients at higher risk for early locoregional recurrence who might benefit from more aggressive therapy. The role of mTOR inhibitors in multimodality or multitarget strategies against laryngeal SCC warrants investigation.     

RET finger protein expression in invasive breast carcinoma: Relationship between RFP and ErbB2 expression

RET finger protein (RFP), which belongs to the large B-box RING finger protein family, has been reported to be expressed in breast carcinoma cell lines. We conducted this study to evaluate the expression level of RFP in breast carcinomas. Tissue microarrays were constructed from 133 cases of invasive breast carcinoma. Sections obtained from tissue arrays and whole sections from 10 non-neoplastic breast tissues were stained for ER, PR, ErbB2, and RFP using immunohistochemistry, and ErbB2 gene status was evaluated by FISH. The correlation between various immunohistochemical markers was determined. We found nuclear RFP expression in 41.4% of invasive carcinomas and in none of the non-neoplastic breast tissues. We also stained whole sections of 29 cases of invasive breast carcinoma, which included the TMA study, and 10 cases of ductal carcinoma in situ (DCIS) by RFP. We observed that four (40%) of the DCIS cases were positive with RFP. In statistical analysis, there was a significant, positive association between RFP and ErbB2 status at the protein level (p=0.002) and the gene level (p=0.049). There was no statistically significant association between the expression of RFP and tumor size, LN status, ER, PR, and grade (p>0.05). However, we found a significant association between age and RFP expression. RFP expression was stronger in patients 50 years or older (p=0.048). In our study, the expression of RFP correlated strongly with ErbB2 status. Our study is the first in the literature to show expression of RFP in patients with breast carcinoma. However, the possible role of RFP in breast carcinogenesis needs to be investigated in more detailed clinical and experimental studies.