肺腺癌组织EGFR突变与p53和COX-2表达相关性及其临床意义

目的 针对表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变的酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗已成为肺癌精准治疗的典范,但多数患者在EGFR-TKI治疗有效后的8～16个月不可避免会出现获得性耐药.本研究探讨p53和COX-2在EGFR突变型晚期肺腺癌组织中的表达及其与患者临床特征的关系,并观察其表达对EGFR-TKI疗效的影响.方法 选取2014-03-01-2016-01-31于郑州大学第二附属医院病理确诊为EGFR突变型晚期肺腺癌并接受EGFR-TKI治疗的43例患者,利用免疫组织化学法检测p53和COX-2在EGFR突变型晚期肺腺癌组织中的表达;x2检验分析其与临床特征之间的相关性;生存分析采用Kaplan-Meier法;并进一步对影响患者无进展生存期(progression-free survival,PFS)的因素采用Cox比例风险回归模型分析.结果 43例EGFR突变型晚期肺腺癌患者中,p53、COX-2表达阳性率分别为41.8％和53.4％.p53表达随年龄增长(x2=3.939,P=0.047)及肿瘤分化程度减低(x2=4.182,P=0.041)而升高.COX-2表达与年龄、性别、吸烟史、肿瘤分化程度、临床分期及EGFR基因突变类型均未见明显相关性(P＞0.05).p53与COX-2表达无明显相关性,P＞0.05.患者接受EGFR-TKI治疗后,p53阴性组和阳性组中位PFS分别为12.0和7.5个月,差异有统计学意义,x2=4.726,P=0.030;COX-2阴性组和阳性组中位PFS分别为12.0和10.0个月,差异有统计学意义,x2=5.578,P=0.018.进一步行多因素Cox比例风险回归模型分析显示,p53 (HR=0.450,P=0.046)和COX-2(HR=0.424,P=0.021)表达均为EGFR突变型晚期肺腺癌患者PFS的独立影响因素.结论 EGFR突变型晚期肺腺癌组织中,p53和COX-2表达可能促进肿瘤进展,有望成为EGFR-TKI疗效的预测因子.     

Elevation of cyclooxygenase-2 is related to lymph node metastasis in adenocarcinoma of uterine cervix

In a previous study, we demonstrated that elevation of COX-2 is significantly associated with lymph node metastasis in squamous cell carcinoma (SCC) of cervix. The main objective of this study is to characterize the relationship between elevation of COX-2 and its possible clinical role in adenocarcinoma (AC) of cervix. Using immunohistochemistry, we examined COX-2 expression levels in 84 patients with AC of uterine cervix [71 ACs, 13 adenosquamous carcinomas (ASCs)]. Elevation of COX-2 was correlated with clinicopathological variables and p53 expression, as detected by immunohistochemistry. Elevation of COX-2 was detected in 13.0% (11 of 84) of the tumors. Elevation of COX-2 was significantly correlated with histologic type (AC 8.5% vs. ASC 38.5%, P=0.011). Both tumor stage and lymph node metastasis were correlated with elevation of COX-2 with a borderline significance (P=0.062 and 0.068, respectively). Elevation of p53 was not associated with elevation of COX-2. The association between lymph node metastasis and elevation of COX-2 was stronger in cases of AC than in cases of ASC (28.4 vs. 4.3%, P=0.023). According to the results of univariate analysis, elevation of COX-2 was significantly associated with decreased overall survival (P=0.003, log-rank test). However, multivariate analyses revealed that only tumor stage was independently associated with overall survival, suggesting that elevation of COX-2 itself may not be an independent prognostic factor. The present study shows that elevation of COX-2 may contribute to lymph node metastasis in AC of uterine cervix. This suggests that the potential therapeutic role of COX-2 inhibitors should be validated, not only in SCC, but also in AC of uterine cervix.     

非小细胞肺癌中Bcl-2和COX-2表达的预后意义

目的探讨Bcl-2和COX-2表达与非小细胞肺癌(non-smallcelllungcanc-er,NSCLC)预后的关系。方法将88例NSCLC及10例正常肺组织标本制作成组织芯片,应用免疫组织化学SP法检测Bcl-2和COX-2的表达,并与临床病理特征及长期生存进行比较分析。结果Bcl-2胞质和胞核阳性表达率分别为54.5%和42.0%,COX-2胞质阳性表达率为71.6%,而正常肺组织均为阴性,NSCLC患者的Bcl-2胞质和胞核表达和COX-2表达明显高于正常肺组织,P值分别为0.001、0.012和0.000。Bcl-2胞质表达在男性、吸烟者、鳞癌、无淋巴结转移者中表达升高,P值分别为0.001、0.000、0.000和0.002,而与年龄、分化程度和肿瘤大小无关。Bcl-2胞核表达在女性、不吸烟者、腺癌和肿瘤大小为T3和T4者中表达升高,P值分别为0.001、0.006、0.000和0.025,而与年龄、分化程度和淋巴结是否转移无关。COX-2在女性、不吸烟者、腺癌和淋巴结转移阳性者中表达升高,P值分别为0.005、0.027、0.001和0.003,与年龄、分化程度和肿瘤大小无关。Bcl-2胞质表达的患者生存时间更长,而Bcl-2胞核表达的患者生存时间更短。COX-2表达者生存时间短。多因素分析显示,Bcl-2和COX-2不是影响NSCLC预后的独立危险因素。结论NSCLC患者中Bcl-2胞质和胞核表达可能具有相反的预后意义,Bcl-2胞质表达者预后好,而Bcl-2胞核表达者预后差,COX-2阳性表达者预后差,两者联合检测可能在NSCLC预后判定中有重要作用。     

COX-2、VEGF在胃癌中的表达及其预后意义

目的 :研究COX 2、VEGF表达对胃癌的预后意义。方法 :收集我院 1990～ 1999年早、中期胃癌 2 81例 ,对有完整存档蜡块资料的 2 32例进行免疫组织化学染色。检测COX 2、VEGF及MVD在胃癌组织中的表达 ,并分析其预后意义。结果 :胃癌组织中COX 2、VEGF阳性表达的MVD值均显著高于COX 2、VEGF阴性表达者(P <0 0 1) ;COX 2、VEGF阳性表达及MVD值与胃癌淋巴结转移、血管浸润均密切相关 (P <0 0 1) ;COX 2、VEGF阳性表达者五年生存率明显低于阴性者 (P <0 0 1)。多因素分析显示 ,VEGF表达、淋巴结转移、COX 2表达、浸润深度、血管浸润均为胃癌独立的预后因素。结论 :COX 2、VEGF在胃癌组织呈过度表达状态 ,与胃癌的生长和浸润转移关系密切 ,可以作为反映胃癌生物学行为和判断预后的有效指标。     

Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

Oesophageal adenocarcinoma is an aggressive malignancy with propensity for early lymphatic and haematogenous dissemination. Since conventional TNM staging does not provide accurate prognostic information, novel molecular prognostic markers and potential therapeutic targets are subject of intense research. The aim of the present study was to study the prognostic significance of Met, the hepatic growth factor (HGF) receptor and a possible target for therapy in comparison to cyclooxygenase-2 (COX-2). Tumour sections from 145 consecutive patients undergoing intentionally curative surgery for oesophageal adenocarcinoma were immunohistochemically analysed for Met and COX-2 expression. Clinicopathological data were prospectively collected for all patients. Patients with high Met expression had significantly reduced overall and disease-specific 5-year survival rates (P< or =0.001 and P< or =0.001, respectively) and were more likely to develop distant metastases (P=0.002) and local recurrences (P=0.004) compared to patients with low Met expression. High COX-2 expression tended to be correlated with poor long-term survival but this did not reach statistical significance. Expression of Met was recognised as a significant and independent prognostic factor by stage-specific analysis and multivariate analysis (relative risk=2.3; 95% CI=1.3-4.1). These findings support the importance of Met in oesophageal adenocarcinoma and support the concept of Met tyrosine kinase inhibition as (neo-) adjuvant treatment.     

食管癌组织芯片COX-2和survivin表达及其 与预后的关系

 目的研究食管癌组织中COX-2和survivin蛋白的表达,及其预后意义。方法采用免疫组化EnVision法和组织芯片技术,检测手术切除的56例食管癌组织中COX-2和survivin蛋白的表达状况,通过Cox比例风险模型进行多因素分析,探讨与食管癌患者预后的关系。结果COX-2和survivin在食管癌组织阳性表达率分别为69.6％和71.4％。COX-2和survivin表达呈正相关（r=0.614,P=0.002）,且与肿瘤浸润深度、淋巴结转移及TNM分期密切相关。COX-2表达阳性患者的中位生存时间明显短于阴性患者（25.13月 vs.69.33月,P=0.0001）,survivin表达阳性患者的中位生存时间明显短于阴性患者（25.23月vs. 69.32月,P=0.0000）。Cox多因素分析表明,COX-2和survivin蛋白阳性表达为影响食管癌患者预后的独立因素。结论COX-2和survivin在食管癌中呈过度表达,且呈正相关,二者在肿瘤中可能发挥协调作用。COX-2和survivin高表达预示食管癌的不良预后,可以作为影响食管癌患者预后的独立因素。     

COX-2、NF-κB、WT-1、PTEN在恶性腹膜间皮瘤中的表达及与预后的关系

目的 研究恶性腹膜间皮瘤组织中环氧合酶-2（COX-2）、核因子-κB（NF-κB）、Wilm’s 瘤基因-1（WT-1）、PTEN的表达及与预后的关系。方法 选取2011—2013年经病理确诊的恶性腹膜间皮瘤33例,应用免疫组织化学SP法检测病变腹膜组织中COX-2、NF-κB、WT-1及PTEN的表达,并分析与年龄、性别、血小板升高、石棉接触、CA125升高、腹水、淋巴结转移、临床分期等指标的关系。对所有患者进行随访,分析标志物与预后的关系。结果 33例恶性腹膜间皮瘤中,COX-2、NF- κB、WT-1及PTEN的阳性表达率分别为63.64%、51.52%、72.73%和21.21%。4项指标与年龄、性别、血小板升高、石棉接触、CA125升高、腹水、淋巴结转移、临床分期均无相关性（P>0.05）。COX-2 和NF-κB分别与PTEN呈负相关。单因素和多因素生存分析显示,PTEN阴性表达患者生存时间短, 而COX-2与NF-κB阳性表达患者生存时间短。PTEN是影响恶性腹膜间皮瘤预后的独立风险因素。结 论 高表达COX-2及NF-κB提示预后不良,PTEN是影响恶性腹膜间皮瘤的独立预后因素。     

VEGF-C、COX-2在细支气管肺泡癌中的表达及其意义

目的探讨细支气管肺泡癌（BAC）中VEGF．C、COX-2蛋白表达及意义。方法BAC60例为实验组,肺腺癌伴BAC20例和肺腺癌22例为对照组,采用免疫组化法分别检测VEGF—C、COX-2蛋白在3种组织中的表达并分析其临床意义。结果VEGF．C在BAC、肺腺癌伴BAC和肺腺癌中阳性率分别为66．7％、90．0％和95．5％,各组间表达差异有统计学意义（P〈0．05）;VEGF—C在BAC非黏液型表达阳性率显著高于黏液型（P〈0．05）,伴淋巴结转移组阳性率明显高于无转移组（P〈0．05）,VEGF—C表达与性别、年龄、肿块部位、大小及TNM分期均无关联（P〉0．05）。COX-2在BAC、肺腺癌伴BAC和肺腺癌中阳性率分别为63．3％、75．0％和77．3％,各组间表达差异无统计学意义（P〉0．05）;COX-2在BAC伴淋巴结转移组表达阳性率明显高于无转移组（P〈0．05）,肿块直径≥3cm组阳性率明显高于肿块直径〈3cm组（P〈0．05）,COX-2表达与性别、年龄、肿块部位、病理类型及TNM分期均无关（P〉0．05）。VEGF-C与COX-2表达呈正相关（r=0．269,P〈0．05）。结论VEGF—C联合COX-2检测可用于BAC侵袭、转移特性的评估及预测。     

Prognostic role of cyclooxygenase-2 in neoadjuvant-treated patients with squamous cell carcinoma of the esophagus

Based on our previous demonstration that elevated cyclooxygenase-2 (COX-2) expression is a prognostic factor for reduced survival in patients with adenocarcinoma of the esophagus, the aim of our study was to analyze the role of COX-2 expression in esophageal squamous cell carcinoma. We analyzed COX-2 protein expression from 117 consecutive patients by immunohistochemistry using a COX-2 specific monoclonal antibody. Eighty-one patients had not received any therapy before surgery whereas 36 patients received neoadjuvant chemotherapy as part of a randomized controlled trial. In the patients who received no chemotherapy, COX-2 expression was low in 75% and high in 25% of the specimens. In this patient group, high COX-2 expression associated with distal location of the tumor (p = 0.02), but did not correlate with any other clinicopathological parameter tested, including overall survival. In the patient group who received neoadjuvant chemotherapy, postoperative COX-2 expression was low in 69% and high in 31%. Interestingly, in this patient group low COX-2 expression correlated with development of distant metastases (p = 0.03) and to reduced overall survival (p = 0.02). Our results show that the prognostic significance of COX-2 depends on the histological type of esophageal carcinoma and preoperative treatment of the patient. In conclusion, COX-2 is not a prognostic marker in squamous cell carcinoma of the esophagus, but low COX-2 expression is associated with poor prognosis in the neoadjuvant-treated patients.     

Prognostic evaluation of the expression of p53 and bcl-2 oncoproteins in patients with surgically resected non-small cell lung cancer

BACKGROUND: Tumor staging remains the most important prognostic predictor in patients with non-small cell lung cancer (NSCLC). However, the prognostic significance of expression of oncoproteins involved in regulation of cellular uncontrolled proliferation remains controversial. METHODS: In this retrospective study, we investigated the expression of bcl-2 and p53 oncoproteins in 114 surgically resected NSCLC patients (46 stage I, 39 stage II and 29 stage IIIa) using immunohistochemical analysis and correlated the molecular markers with survival. RESULTS: Positive bcl-2 immunoreactivity was detected in 26 of 114 (22.8%) NSCLC, including 15 of 43 (34.9%) squamous cell carcinoma and 11 of 71 (15.5%) adenocarcinoma cases. Nuclear staining for p53 was observed in 59 of 114 (51.8%) NSCLC, including 26 of 43 (60.5%) squamous cell carcinoma and 33 of 71 (46.5%) adenocarcinoma patients. There was no correlation between pathological staging and expression of bcl-2 and p53. However, the expression frequency of bcl-2 was significantly higher in squamous cell carcinoma than in adenocarcinoma (P < 0.02). The presence of bcl-2 expression did not provide a favorable prognosis (P = 0.23) and the overexpression of p53 oncoprotein was also not significantly associated with adverse prognosis (P = 0.09). No inverse relationship was found between bcl-2 and p53 expression (P = 0.83). CONCLUSION: Expressions of bcl-2 and p53 using immunohistochemical staining are not independent prognostic predictors in patients undergoing surgery for NSCLC.     

Total cyclooxygenase-2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non-small cell lung cancer patients

Interaction between cancer cells and adjacent stromal cells is important to promote tumor development. Our aim was to study total COX-2 mRNA expression in both cancer cells and surrounding stromal cells and its association with angiogenic factor VEGF mRNA expression, tumor angiogenesis and prognosis in patients with NSCLC. COX-2 mRNA expression in both cancer cells and stromal tissue was analyzed using real-time quantitative (RTQ) RT-PCR in 60 NSCLC surgical specimens. Immunohistochemistry (IHC) was used to localize COX-2 protein in tumor specimens. Correlations between tumoral total COX-2 mRNA expression and VEGF mRNA expression (measured by RTQ RT-PCR), intratumoral microvessel counts (evaluated by IHC), other clinicopathologic variables, survival and relapse were tested. COX-2 protein expression was found in cancer as well as the surrounding stromal cells (including infiltrating inflammatory cells and endothelial cells of tumor-associated microvessels). VEGF protein expression was mainly located in cancer cells. There was a significant association between high tumoral total COX-2 mRNA expression and high VEGF mRNA expression (p = 0.01) or high intratumoral MVC (p < 0.001) but not other clinicopathologic variables, including tumor status and lymph node metastasis. Patients with higher tumoral total COX-2 mRNA expression had a statistically shorter survival time (median 15.0 +/- 2.61 months) and relapse time (median 5.0 +/- 1.37 months) than those with lower tumoral total COX-2 mRNA expression (median 40.0 +/- 3.12 and 34.0 +/- 3.11 months; p < 0.0001 and p < 0.0001, respectively, log-rank test). A significant difference in survival and relapse time was also seen between patients with high and low tumoral VEGF mRNA expression and between those with high and low intratumoral MVC (p = 0.0046 and p = 0.0038, respectively). After stratification by disease stage or histologic subtype, the prognostic significance of high total COX-2 mRNA expression was still apparent in both stage I and stage II-IV and in both squamous cell carcinoma and adenocarcinoma (p < or = 0.01 for all). Multivariate analysis using the Cox regression model with backward elimination showed that tumoral total COX-2 mRNA expression and lymph node status were the 2 most important independent prognostic predictors for survival and disease relapse. We report that total COX-2 mRNA expression in cancer cells and surrounding stromal cells correlates strongly and positively with VEGF mRNA expression, intratumoral MVC and adverse prognosis in NSCLC patients. This implies that COX-2 expression in both cancer cells and stromal cells within the tumor microenvironment may play an important role in upregulating the expression of the angiogenic factor VEGF and tumor angiogenesis in NSCLC and explains, in part, the adverse prognostic effect of COX-2 overexpression in patients with NSCLC.     

COX-2和survivin蛋白在非小细胞肺癌中的表达情况及临床意义

目的 探讨环氧化酶-2(COX-2)和凋亡抑制蛋白(survivin)在非小细胞肺癌中的表达情况及对预后的影响.方法 选取85例非小细胞肺癌患者,收集患者的肿瘤组织及癌旁组织,通过免疫组织化学染色法检测两种组织中COX-2和survivin蛋白的表达情况,分析其与患者临床特征的关系及预后情况.结果 非小细胞肺癌组织中COX-2和survivin的平均光密度均高于癌旁组织,差异均有统计学意义(P﹤0.05);COX-2的阳性表达率为64.71%,survivin的阳性表达率为58.82%;COX-2和survivin的阳性表达率在不同年龄和性别的非小细胞肺癌患者中比较,差异均无统计学意义(P﹥0.05);肿瘤直径≥4 cm、低分化、Ⅲ~Ⅳ期、有淋巴结转移和有吸烟史患者的COX-2和survivin阳性表达率明显高于肿瘤直径﹤4 cm、中高分化、Ⅰ~Ⅱ期、无淋巴结转移和无吸烟史的患者(P﹤0.01).COX-2和survivin阳性表达的非小细胞肺癌患者的中位生存期均明显短于阴性表达的患者(P﹤0.01).结论 COX-2和survivin蛋白在非小细胞肺癌组织中高表达,可能参与了非小细胞肺癌的发生和发展,COX-2和survivin高表达患者的预后较差.     

Survival in small cell lung cancer is independent of tumor expression of VEGF and COX-2

BACKGROUND: Preclinical data suggests that VEGF and COX-2 are potentially important mediators in the pathogenesis of small cell lung cancer (SCLC). Little is known about the frequency of tumor expression of VEGF and COX-2 in SCLC or the prognostic significance of this expression. MATERIALS AND METHODS: Clinical records from 54 cases of SCLC were reviewed. Immunohistochemical stains for VEGF and COX-2 were performed on all tumor specimens. RESULTS: Tumor VEGF expression was detected in 43 cases (81%) and COX-2 expression in 11 (20%). No significant association between VEGF or COX-2 expression and survival was observed. CONCLUSION: This is the first study to assess the frequency and clinical significance of tumor VEGF and COX-2 expression in a large group of patients with SCLC. In this cohort, neither VEGF nor COX-2 expression impacted survival. The frequency of VEGF expression suggests that it merits further investigation as a therapeutic target in SCLC.     

Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell lung cancer

The role of COX-2 expression and angiogenesis of lung cancer is yet to be delineated. Eighty four non-small cell lung cancer (NSCLC) specimens were evaluated for COX-2 expression, microvessel density (MVD), and vascular endothelial growth factor (VEGF) expression by immunohistochemical methods. The relationships between COX-2 expression and MVD, VEGF expression, and survival time were analyzed. COX-2 expression was observed in the cytoplasm and membrane of the carcinoma cells, and premalignant cells. COX-2 was positive in 67 cases (79.8%). There was a statistically significant correlation between COX-2 expression and tumor size, TNM stage, tumor type, VEGF expression, and vascular pattern with survival in univariate analysis. No significant correlation was seen between COX-2, VEGF expression and MVD. A lack of expression of either COX-2 or VEGF expression or both, however, was associated with lower MVD than the group with both expressed. The difference was statistically significant (P=0.005). Statistically significant differences were also observed according to TNM stage, vascular pattern, COX-2 expression, and VEGF expression. With multivariate analysis, only TNM stage and COX-2 expression retained their significance as independent predictors of survival. COX-2 expression takes part in tumor angiogenesis and is a significant poor prognostic factor in the surgically resected NSCLC. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.     

Significance of cyclooxygenase 2 and MDR1/P-glycoprotein coexpression in ovarian cancers

Immunohistochemical analysis of prognostic significance of COX-2 and P-gp expression in ovarian cancers was performed on samples originating from 73 tumors. COX-2-positive cases were shown to demonstrate higher expression of P-gp. The studies demonstrated also that, higher P-gp expression was typical for cases which responded poorly to chemotherapy and for cases with shorter progression-free time. Expression of COX-2 predisposed to a more rapid disease progression. The study documented a relationship between COX-2 and P-gp suggesting that COX-2 inhibitors might investigated in clinical trials as a treatment supplementary to chemotherapy of ovarian cancers.     

Increased cyclooxygenase 2 (COX-2) expression occurs frequently in precursor lesions of human adenocarcinoma of the lung

A low incidence of lung carcinoma has been reported in cases of prolonged use of aspirin. Cyclooxygenase (COX) 2 expression is frequently seen in adenocarcinoma of the lung, but COX-2 expression in atypical adenomatous hyperplasia (AAH), a possible precursor lesion of adenocarcinoma of the lung, is not known. COX-2 expression was immunohistochemically evaluated in a cohort of 20 cuboidal cell hyperplasias (CCH), 81 atypical adenomatous hyperplasias (AAH), 18 bronchioloalveolar carcinomas (BAC), and 88 invasive adenocarcinomas (I-Ad). The relationship between COX-2 expression and clinicopathologic factors and survival was examined. COX-2 overexpression was detected in over 80% of CCH, AAH, BAC, and I-Ad. However, overexpression was diffuse in AAH (71.6%) and BAC (66.7%). No relationship was found between COX-2 expression and clinicopathological factors or survival. COX-2 expression was most frequently detected in AAH. These findings, taken with previous reports that treatment with COX-2 inhibitor suppresses human colon carcinogenesis, suggest that inhibition of COX-2 may reduce the incidence of human adenocarcinoma of the lung.     

胰岛素样生长因子2的表达对N2期肺腺癌预后的影响

本研究探讨了IGF2在N2期肺腺癌组织中的表达及其对预后的影响。方法：回顾性分析90例未行新辅助化疗的N2期肺腺癌患者情况,利用石蜡标本组织制成组织芯片,行免疫组化检测,研究影响N2期肺腺癌的预后因素,以及IGF2的表达对预后的影响。结果：N2期肺腺癌手术后的5年生存率与隆突下淋巴结是否转移、T分期及纵隔淋巴结转移站数有关。IGF2在N2期肺腺癌中表达的阳性率是68.9%。IGF2阳性表达的N2期肺腺癌的5年生存率为8.0%,IGF2阴性表达的N2期肺腺癌的5年生存率为18.0%,两者有显著性差异（P=0.034）。结论：N2期肺腺癌的预后差,影响其预后的临床因素包括T分期、纵隔淋巴结转移站数和隆突下淋巴结转移。IGF2表达有预测N2期肺腺癌预后的作用。     

Cyclooxygenase-2 expression in endometrial carcinoma: correlation with clinicopathologic parameters and clinical outcome

BACKGROUND: Cyclooxygenase-2 (COX-2) is overexpressed in endometrial hyperplasia and carcinoma, but no data have been reported until now about the expression of COX-2 and its possible clinical significance in endometrial carcinoma. We investigated by immunohistochemistry the expression of COX-2 in a single institutional series of primary untreated endometrial carcinoma patients. The relationship between COX-2 expression and microsatellite instability (MI) status was also analyzed. METHODS: The study was conducted on 69 primary untreated endometrial carcinoma patients who were admitted to the Department of Obstetrics and Gynecology, Catholic University of Rome. Immunohistochemistry was performed by using rabbit polyclonal antiserum against human COX-2. Analysis of MI was performed for 47 patients with endometrial carcinomas. RESULTS: Twenty-seven patients (39.1%) were scored as COX-2 positive. COX-2 positivity was higher (60.8%) in endometrial carcinoma with cervical or extrauterine involvement than in tumors limited to the corpus (28.3%; P = 0.0174). COX-2 positivity increased from Grade 1 (13.6%) to Grade 2 (41.7%) to Grade 3 (60.9%) endometrial carcinoma (P = 0.0049). Interestingly, considering early International Federation of Gynecology and Obstetrics stage patients (n = 53), the percentage of COX-2 positivity was higher in patients with deep myometrial invasion (66.7%) than in patients without or less than 50% myometrial invasion (15.6%) (P = 0.0003). No association between COX-2 and MI status was found. COX-2-positive patients showed a trend to a shorter disease-free survival than COX-2-negative patients (P = 0.09). CONCLUSIONS: COX-2 is expressed in a high percentage of a large series of primary endometrial tumors and its expression may be associated closely with parameters of tumor aggressiveness The possible prognostic role of COX-2 in endometrial carcinoma deserves further study.