Distant lymph node metastasis of early gastric cancer

Among 601 patients with early gastric cancer (EGC), the clinicopathological findings of 5 patients (invasion of the mucosal layer in 2 and of the submucosal layer in 3) with distant lymph node metastasis according to TNM classification (third-or fourth-tier lymph node metastasis according to the Japanese classification) were investigated. The proliferating-cell nuclear antigen (PCNA) expression of EGC was also examined immunohistologically. The sites of distant metastasis were the nodes at the root of the mesentery, in the hepatoduodenal ligament, and the paraaortic nodes, while the PCNA-positive rate of EGC with distant lymph node metastasis (35.4%) was significantly higher than that of EGC without lymph node metastasis (14.7%,P=0.01), it was similar to that of EGC with perigastric lymph node metastasis. The cumulative survival rate of the EGC patients with distant lymph node metastasis (5-year survival rate 20.0%) was significantly lower than that without lymph node metastasis (88.2%,P<0.0001), first-tier lymph node metastasis (76.9%,P<0.04), or second-tier lymph node metastasis (77.1%,P<0.04). Thus, although the prognosis of EGC patients with distant lymph node metastasis was poor, a dissection of the distant lymph nodes should be performed when metastasis is suspected.     

Angiogenesis as an unfavorable factor related to lymph node metastasis in early gastric cancer

Background: Recent studies suggest that angiogenesis enhances tumor growth and metastasis. Lymph node metastasis influences the prognosis and selection of treatment modalities in cancers. In this study, the authors investigated the correlation between angiogenesis and clinicopathologic features to determine whether angiogenesis correlated with lymph node metastasis in early-stage gastric cancer. Methods: A total of 97 specimens from patients with early gastric cancer were studied by immunohistochemical methods using anti-Factor VIII-related antigen antibody. Results: Tumor size was significantly correlated with microvessel count, which increased as tumor size increased. Microvessel counts from tumors with lymphatic vessel invasion, lymph node metastasis, and submucosal invasion were significantly higher than those without. Furthermore, microvessel count was an independent factor that influenced lymph node metastasis (P=.0016) by multivariate logistic regression analysis. Conclusion: In the early stage of gastric carcinoma, angiogenesis is an independent factor that impacts on lymph node metastasis.     

HIF-1α及VEGF-C在食管癌中的表达及意义

目的探讨缺氧诱导因子-1α(HIF-1α)及血管内皮生长因子C(VEGF-C)在食管癌中的表达及其与食管癌淋巴转移的关系。方法采用免疫组织化学法检测55例食管鳞状细胞癌(ESCC)组织及癌旁组织中HIF-1α、VEGF-C表达及微淋巴管密度(MLVD)的分布情况;运用SPSS12.0软件包进行统计学分析,率的比较采用χ2检验、两组均数的比较采用t检验,显著性水准取α=0.05。结果HIF-1α、VEGF-C在食管癌组织和癌旁组织中的表达阳性率分别为65.5%/10.9%、70.9%/9.1%,差异均有统计学意义(P<0.01);癌组织和癌旁组织的微淋巴管密度分别为4.9±1.3和2.6±0.7,差异有统计学意义(P<0.05);食管癌组织中HIF-1α与VEGF-C表达有统计学关联(P<0.05)。结论HIF-1α、VEGF-C在食管癌的发生发展和淋巴转移中起重要作用,有望成为食管癌治疗和判断预后的重要指标。微淋巴管的形成可能会促进食管癌经淋巴结转移的发生,MLVD可作为判断食管癌淋巴转移和预后的分子指标。HIF-1α可能通过上调VEGF-C的表达,进而通过VEGF/VEGFR信号系统,对肿瘤淋巴管形成调控,促进食管癌淋巴管生成,并导致肿瘤浸润和淋巴结转移。     

Tumor Recurrence following Resection for Early Gastric Carcinoma and Its Implications for a Policy of Limited Resection

p < 0.02) more recurrent than mucosal ones (0.29%). Of the 16 patients with recurrence, 10 (62.5%) died within 5 years after surgery, frequently because of blood-borne metastasis. Macroscopically elevated components, the degree of histologic differentiation, and lymph node metastasis significantly contributed to the postoperative recurrence. After detailed analysis of submucosal carcinomas, it is strongly suspected that carcinomas with a macroscopically elevated component were significantly associated with nodal involvement and microvessel invasion, and that these abnormalities lead to recurrence. Among the early gastric carcinomas, differentiated submucosal carcinomas with a macroscopically elevated component, lymph node metastasis, or both have the most potential of recurrence after surgery. Mucosal carcinomas must be restricted to limited surgery, but, blood-borne metastasis should be carefully avoided.     

h-prune Is an Independent Prognostic Marker for Survival in Esophageal Squamous Cell Carcinoma

Background  The human homologue of Drosophila prune (PRUNE, which encodes h-prune) protein interacts with glycogen synthase kinase 3 and promotes cell motility. The aim of our study was to investigate the impact of immunohistochemically detected h-prune expression on the survival of patients with esophageal squamous cell carcinoma (ESCC). Methods  Immunohistochemical staining of h-prune was performed for 205 surgically resected specimens of ESCC. Results  In total, 43 (21%) of 205 ESCC cases were positive for h-prune. h-prune-positive ESCC cases showed a more-advanced T stage (P < 0.0001), N stage (P < 0.0001), and tumor stage (P < 0.0001) than h-prune-negative ESCC cases. In the group of 116 stage II and III ESCC cases, recurrence of ESCC was frequently found in h-prune-positive cases. In patients with lung recurrence, the tumors were more likely to be h-prune positive than h-prune negative. Univariate analysis revealed that T stage (P < 0.0001), N stage (P < 0.0001), tumor stage (P < 0.0001), and h-prune staining (P < 0.0001) were significant prognostic factors for survival. Multivariate analysis indicated that N stage (P = 0.0182) and h-prune staining (P < 0.0001) were independent predictors for survival. Conclusions  These results indicate that immunostaining of h-prune is useful to identify patients at high risk for recurrence or poor prognosis associated with ESCC.     

Correlation Between Vascular Endothelial Growth Factor C Expression and Lymph Node Metastasis in T1 Carcinoma of the Colon and Rectum

Purpose. Vascular endothelial growth factor C (VEGF-C) is known to be associated with the development of the lymphatic vessel system. Recently, VEGF-C is thought to be correlated with lymph node metastasis in some malignant tumors. In this study, we investigated the correlation between VEGF-C expression and lymph node metastasis in early carcinoma of the colon and rectum. Methods. Two hundred and twenty-one endoscopically biopsied specimens from patients with T1 colorectal carcinoma prior to operation were investigated by an immunohistochemical study. Results. VEGF-C expression was more frequently observed in the tumors with nodal metastasis than in those without metastasis. Moreover, a multivariate analysis indicated that VEGF-C expression is an independent predictor of lymph node metastasis. Conclusion. VEGF-C staining using endoscopically biopsied specimens prior to operation could be of use in the prediction of lymph node metastasis and in preoperative selection of treatment in patients with T1 colorectal carcinoma.     

Predictive factors for lymph node metastasis in early gastric cancer with signet ring cell histology and their impact on the surgical strategy: analysis of single institutional experience

Background

The prognosis of early gastric cancer (EGC) with signet ring cell histology is more favorable than other undifferentiated gastric adenocarcinomas. An accurate assessment of potential lymph node metastasis is important for the appropriate treatment of EGC with signet ring cell histology. Therefore, this study analyzed the predictive factors associated with lymph node metastasis in patients with this type of EGC.

Methods

A total of 136 EGC with signet ring cell histology patients who underwent D2 radical gastrectomy were reviewed in this study. The clinicopathologic features were analyzed to identify predictive factors for lymph node metastasis.

Results

The overall rate of lymph node metastasis in EGC with signet ring cell histology was 10.3%. Using a univariate analysis, the risk factors for lymph node metastasis were identified as the tumor size, depth of tumor invasion, and lymphovascular invasion. The multivariate analysis revealed that tumor size >2 cm, submucosal invasion, and lymphovascular invasion were independent risk factors of lymph node metastasis (P < 0.05).

Conclusions

The risk of lymph node metastasis of EGC with signet ring cell histology was high in those with tumor sizes ≥2 cm, submucosal tumors, and lymphovascular invasion. A minimally invasive treatment, such as endoscopic resection, might be possible in highly selective cases of EGC with signet ring cell histology with intramucosal invasion, tumor size <2 cm, and no lymphovascular invasion.     

Prognostic Significance of Immunohistochemically Detected Blood and Lymphatic Vessel Invasion in Colorectal Carcinoma: Its Impact on Prognosis

Background The prognostic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) is unclear. Because of the absence of specific markers for venous and lymphatic vessels, earlier studies could not reliably distinguish between BVI and LVI. Methods By immunostaining for podoplanin and CD34 antigen, we retrospectively investigated LVI and BVI in 419 tissue specimens of colorectal carcinoma. We performed univariate and multivariate analysis of the clinicopathologic features, frequency of recurrence, and outcome of patients with or without LVI and BVI. Results The use of hematoxylin and eosin (H&E) staining to identify BVI and LVI yielded a false positive rate of 9.1% and false negative rate of 12.6%. The incidence of BVI was significantly higher among tumors with LVI than tumors without LVI (P <.001). In logistic multivariate analysis, only LVI (P < .001) was associated with lymph node metastasis and BVI (P = .015) was associated with distant recurrence. Calculating the prognostic relevance, both two invasion types correlated with decreased survival in univariate analysis (both P <.001). In multivariate analysis, BVI (P =.024), lymph node status (P =.003) and tumor stage (P <.001) remained statistically significant factors for survival. Conclusions Our results suggest that immunohistologic evaluation of BVI and LVI could be useful in colorectal carcinoma indicating the risk of lymph node metastasis and recurrence, thereby contributing to prognostic evaluation.     

Carcinomatous Lymphatic Invasion in Early Gastric Cancer Invading Into the Submucosa

Background: Lymphatic invasion is a risk factor for lymph node metastases in patients with gastric cancer. No studies have been reported, however, on the correlation between lymphatic invasion and lymph node metastasis in early gastric cancer invading into the submucosa.Methods: We performed a retrospective analysis of lymphatic invasion in 170 patients with early gastric cancer invading into the submucosa.Results: Lymphatic invasion was found in 76 patients. Lymphatic invasion correlated significantly with the presence of lymph node metastasis and vascular invasion (P < .05) and with the degree of cancerous submucosal involvement (P < .05). The presence of lymph node metastasis also correlated with the grade of submucosal invasion and lymphatic invasion. The 5-year survival of patients with lymphatic invasion was poorer than that of patients without lymphatic invasion (P < .05). Node-negative patients had similar survival, regardless of the presence of lymphatic invasion. All patients with severe lymphatic invasion had sm3 invasion and lymph node metastases.Conclusion: Although lymphatic invasion is the first stage of lymph node metastasis, lymphatic invasion in itself does not have clinical importance except for severe invasion in early gastric cancer. It is possible to predict lymph node metastases from the combined evaluation of degree of lymphatic invasion and submucosal involvement of the tumor in patients with early gastric cancer invading into the submucosa.     

Analysis of early (pT1) gastric cancer with submucosal invasion: surgical management and possibility to schedule less invasive surgery

Background: Early gastric cancer (EGC) is one of the popular targets of less invasive surgery. The aim of the present study is to clarify the possibility of scheduling a less invasive surgery for EGC cases with submucosal (SM) invasion.Methods: Eighty cases of EGC with SM invasion were analyzed clinicopathologically and immunohistochemically. Correlations between factors that reflect cancer progression and data from endoscopic examination were investigated.Results: Thirteen cases (16.3%) showed lymph node metastasis and the numbers of metastasis-positive lymph nodes ranged from 1 to 18. Two cases showed lymph node metastasis not only in the perigastric area, but also along the left gastric artery and the common hepatic artery. Only the tumor size showed a significant correlation with lymph node metastasis (P = .014) using the data from preoperative endoscopic examination. With respect to p53 overexpression, there was no significant correlation with pathologic factors in EGC with SM invasion. The simple protuberance types that were <2 cm in diameter had no lymph node metastasis.Conclusions: It seems difficult to predict the progression of EGC with SM invasion from the data currently obtained by preoperative endoscopic examination. It was suggested that less invasive surgery could be scheduled only for simple protuberance type cases that were <2 cm in diameter. Radical gastrectomy and D2 lymph node dissection is required, in open surgery or laparoscopic surgery, for any other type of EGC with SM invasion.     

Vascular endothelial growth factor-C (VEGF-C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder

PURPOSE: It has been found that expression of vascular endothelial growth factor-C (VEGF-C) in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis. However, VEGF-C expression in bladder transitional cell carcinoma (TCC) has not yet been reported. To elucidate the role of VEGF-C in bladder TCC, we examined VEGF-C expression in bladder TCC and pelvic lymph node metastasis specimens obtained from patients who underwent radical cystectomy. METHODS: Eighty-seven patients who underwent radical cystectomy for clinically organ-confined TCC of the bladder were enrolled in the present study. No neoadjuvant treatments, except transurethral resection of the tumor, were given to these patients. The VEGF-C expressions of 87 bladder tumors and 20 pelvic lymph node metastasis specimens were examined immunohistochemically and the association between VEGF-C expression and clinicopathological factors, including angiogenesis as evaluated by microvessel density (MVD), was also examined. RESULTS: Vascular endothelial growth factor-C expression was found in the cytoplasm of tumor cells, but not in the normal transitional epithelium. Vascular endothelial growth factor-C expression was significantly associated with the pathological T stage (P = 0.0289), pelvic lymph node metastasis (P < 0.0001), lymphatic involvement (P = 0.0008), venous involvement (P = 0.0002) and high MVD (P = 0.0043). The multivariate analysis demonstrated that VEGF-C expression and high MVD in bladder TCC were independent risk factors influencing the pelvic lymph node metastasis. Moreover, the patients with VEGF-C-positive tumors had significantly poorer prognoses than those with the VEGF-C-negative tumors (P = 0.0087) in the univariate analysis. The multivariate analysis based on Cox proportional hazard model showed that the independent prognostic factors were patient age (P = 0.0132) and pelvic lymph node metastasis (P = 0.0333). CONCLUSION: The present study suggests that VEGF-C expression is an important predictive factor of pelvic lymph node metastasis in bladder cancer patients.     

High matrix metalloproteinase-to-E-cadherin ratio measured by bicolor fluorescent in situ hybridization is associated with lymphangiogenesis and lymph node metastasis in prostate cancer

ObjectiveThe colorimetric in situ hybridization (CISH)-based matrix metalloproteinase (MMP)-to-E-cadherin (ECD) ratio (MER) has been revealed as an excellent marker for the disease stage in prostate cancer. The one aim of this study was investigating a new method for estimation of MER by bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector-based system. Another aim was examination of relation of MER by bicolor FISH with expression of vascular endothelial growth factor-C (VEGF-C).MethodsThe bicolor FISH technique used cyanin 5 (cy5)-labeled MMP-2 and ?9 probes, and a cyanin 3 (cy3)-labeled ECD probe on needle biopsy specimens from 67 prostate cancer cases. The ISH was followed by computerized detection of the signal intensities and cy5-to-cy3 ratios using a fluorescence detector. VEGF-C expression was examined using cy5-labeled VEGF-C by computerized detection.ResultsThe bicolor FISH-based MER was well correlated with CISH-based MER (P < 0.0001). The bicolor FISH-based MER correlated with Gleason score and pathologic stage of the cases. VEGF-C mRNA expression was associated with the pathologic stage and maximum lymph vessel density (LVD). The LVD was associated with VEGF-C expression at the tumor area where the maximum MER was detected (P < 0.0001).ConclusionThe MER was correlated with the VEGF-C expression and LVD, indicating lymph node metastasis of prostate cancer. Therefore, this computer-assisted MER is a useful marker for preoperative prediction of disease stage, especially lymph node metastasis, of prostate cancer.     

血管内皮生长因子-C在大肠癌中的表达及其与淋巴结转移的关系

目的研究血管内皮生长因子-C(VEGF-C)在大肠癌中的表达,探讨其与淋巴结转移的关系。方法应用免疫组织化学染色法检测94例大肠癌组织标本中VEGF-C的表达,同时应用逆转录-聚合酶链反应(RT-PCR)检测其mRNA在4株大肠癌细胞株中的表达。结果VEGF-C在53.2%的大肠癌患者中呈阳性表达;VEGF-C在淋巴结转移阳性组中的表达,与阴性组比较差异有统计学意义(P<0.01);VEGF-C的表达与淋巴管浸润和Dukes分期密切相关(P<0.01),但与年龄、性别、肿瘤的位置、浸润深度和血管浸润均无明显相关。VEGF-CmRNA表达于大肠癌LoVo及LoVo-5-Fu耐药细胞株。结论VEGF-C的表达可能参与肿瘤淋巴管生成,与大肠癌淋巴结转移密切相关。     

Correlation Between Connexin 26 Expression and Poor Prognosis of Esophageal Squamous Cell Carcinoma

Background  Failure of gap junction formation affects the development of various types of cancer. We aimed to clarify the clinicopathologic outcome and prognostic significance of connexin (Cx) 26 in human esophageal squamous cell carcinoma (ESCC). Methods  Immunohistochemical staining for Cx26 was performed on surgical specimens obtained from 123 patients with ESCC. Results  There was no positive staining for Cx26-specific expression in normal esophageal squamous cells. Primary ESCC with Cx26-positive expression was detected in the cytoplasm of cancer cell nests in 60 cases. Cx26 expression was correlated with N (lymph node metastasis, P = 0.014) and the number of metastatic lymph nodes (P = 0.047). The 5-year survival rates of ESCC patients with Cx26-positive expression were significantly lower than those with Cx26-negative expression (positive, 39.7%; negative, 65.7%; P = 0.007). By multivariate analysis, tumor–node–metastasis (TNM) clinical classification (T, P < 0.001; N, P = 0.002; M, P = 0.046) and Cx26 (P = 0.024) were independent prognosis predictors of ESCC. Conclusions  These results suggest that abnormal expression of Cx26 participates in the progress of ESCC.     

The Chemokine Receptors CXCR4 and CCR7 are Associated with Tumor Size and Pathologic Indicators of Tumor Aggressiveness in Papillary Thyroid Carcinoma

Background  Functional chemokine receptors are expressed in many malignant tumors, including papillary thyroid carcinoma (PTC). These receptors promote tumor growth and metastasis in response to endogenous chemokines. The purpose of this study was to examine the expression of two chemokine receptors—CXCR4 and CCR7—in a series of PTCs. We hypothesized that CXCR4 and CCR7 would correlate with indicators of tumor aggressiveness, including tumor size, extrathyroidal extension (ETE), angiolymphatic invasion (ALI), and lymph node metastasis. Methods  CXCR4 and CCR7, as well as their specific chemokine ligands (CXCL12 and CCL21, respectively), were assessed in 88 PTCs from 65 patients using a semiquantitative measure of immunohistochemical (IHC) staining intensity for each molecule. Staining intensity was compared with clinicopathologic features including patient age, gender, tumor size, multifocality, ETE, ALI, and lymph node metastasis. Differences in CXCR4 and CCR7 mRNA levels were sought in a subset of tumors using gene microarrays and quantitative RT-PCR. [Statistics: t test, Mann-Whitney U test; P < .05]. Results  High-intensity IHC staining for CXCR4 was associated with larger tumor size (P = .02), while PTCs exhibiting ETE, ALI, or lymph node metastasis showed higher-intensity IHC staining for CCR7 than those without (P = .01, .03, and .01, respectively). CCR7 mRNA levels were also higher in tumors with ALI (P = .04). Conclusion  Expression of CXCR4 and CCR7 by PTCs is associated with indicators of tumor aggressiveness, including tumor size, ETE, ALI, and lymph node metastasis. Further studies are necessary to define the mechanisms underlying this association and to determine its potential prognostic and therapeutic implications.     

Therapeutic Value of Lymph Node Dissection in Advanced Gastric Cancer with Macroscopic Duodenum Invasion: Is the Posterior Pancreatic Head Lymph Node Dissection Beneficial?

Background  In advanced gastric cancer (AGC) with duodenum invasion, the posterior pancreatic lymph nodes are susceptible to metastasis because of their proximity to the duodenum. The therapeutic value of lymph node dissection in this area for AGC with macroscopic duodenum invasion remains unclear. Methods  Patients who had undergone curative gastrectomy for lower-third AGC from 1970 to 2004 at the Cancer Institute Hospital were recruited for this study. Clinicopathological data were collected retrospectively, and compared between cases of AGC with duodenum invasion (AGC-DI group) and AGC without duodenum invasion (AGC-nDI group). In the AGC-DI group, the therapeutic value of lymph node dissection was evaluated using a therapeutic index (multiplication of the frequency of metastasis to the station by the 5-year survival rate of patients with metastasis to that station). Results  The AGC-DI group generally had tumors of higher pathological stage, which might account for the poorer 5-year survival rate compared with that of the AGC-nDI group (50.1% versus 68.5%; P = 0.0002). The incidence of lymph node metastasis was higher in the AGC-DI group than that in the AGC-nDI group, including nodes in the posterior pancreatic head (23.9% versus 7.0%, P < 0.0001). In the AGC-DI group, posterior pancreatic head lymph node dissection was of therapeutic value (4.19) equivalent to dissection of second-tier lymph nodes. Conclusions  The dissection of posterior pancreatic head lymph nodes might be effective in AGC with macroscopic duodenum invasion since this has therapeutic value equivalent to that of second-tier lymph node dissection and might improve patients’ long-term outcomes.     

COX-2和VEGF-C表达与NSCLC淋巴转移的关系

目的探讨环氧化酶-2(COX-2)和血管内皮生长因子-C(VEGF-C)表达与淋巴管形成和淋巴结转移之间的关系。方法用免疫组化链霉素抗生物素蛋白-过氧化物酶(SP)法检测65例非小细胞肺癌(NSCLC)及16例正常肺组织中COX-2、VEGF-C及其受体VEGFR-3的表达;以VEGFR-3作标记计数肿瘤LVD,并结合临床病理特征进行统计学分析。结果65例NSCLC中COX-2和VEGF-C表达阳性率分别为76.9%(50/65)、72.3%(47/65)。COX-2表达与淋巴结转移(r=0.489,P<0.01)、临床分期(r=0.354,P<0.05)、VEGF0C(r=0.640,P<0.01)和LVD(r=0.518,P<0.01)呈正相关,而与病理分化程度呈负相关(r=-0.427,P<0.01)。VEGF-C表达与淋巴结转移(r=0.453,P<0.01)、临床分期(r=0.442,P<0.01)和LVD(r=0.624,P<0.01)呈正相关,与病理分化程度也呈负相关(r=-0.525,P<0.01)。结论NSCLC中COX-2与VEGF-C均高表达,COX-2可能通过VEGF-C促进肿瘤淋巴管生成和淋巴结转移。研究COX-2和VEGF-C在肿瘤中的协同作用有助于揭示肿瘤侵袭和转移的机制。     

Lymph Node Status in Patients with Submucosal Gastric Cancer

Background The aim of this study was to clarify the lymph node status in patients with submucosal gastric cancer.Methods Between April 1994 and December 1999, 615 patients with histologically proven submucosal gastric cancer who underwent curative resection were included in this study. The results of the surgery and predictive factors for lymph node metastasis were evaluated by univariate and multivariate analyses. The accuracy of the predictive factors was assessed in a second population of a further 186 patients.Results Lymph node metastasis was observed in 119 patients (19.3%). Multivariate analysis showed that pathologic tumor diameter (≥20 mm) and lymphatic invasion were independent predictive factors for lymph node metastasis. The incidence of lymph node metastasis without these 2 predictive factors was 1.8% (2 of 113), and it was 51.2% (85 of 166) with the 2 predictive factors, 9.5% (14 of 148) in tumors <20 mm in diameter, and 5.3% (22 of 414) in tumors without lymphatic invasion. Among patients with a tumor <20 mm in diameter, the incidence of lymph node metastasis was significantly reduced in those with a differentiated tumor: 4.2% (4 of 95). These results were almost identical to those observed in the second population.Conclusions Lymph node status can be accurately predicted on the basis of pathologic tumor diameter <20 mm, lymphatic invasion (absence), and histological type (differentiated) in patients with submucosal gastric cancer. Less extensive surgery for these patients might be reconsidered after confirmation of the reproducibility of the results of this study by an appropriately designed prospective clinical trial.     

Prognostic Role of PGE2 Receptor EP2 in Esophageal Squamous Cell Carcinoma

Prostaglandin E2 (PGE2), a major cyclooxygenase-2 (COX-2) product, has been shown to affect numerous tumorigenic processes. PGE2 acts through G-protein-coupled receptors designated as EPs. Recently it has been documented that PGE2 promotes colon cancer cell growth via EP2. However, the expression and the prognostic role of EP2 in esophageal squamous cell carcinoma (ESCC) remained unknown. From January 1995 to January 2001, tissue samples from 226 patients with ESCC who underwent esophagectomies at our institutions were collected and made into tissue core arrays for study. EP2 expression was examined by immunohistochemical staining and confirmed by Western blot. The clinicopathologic data were then analyzed. EP2 overexpression was observed in 43.4% (98/226) of ESCC. Overexpression of EP2 correlated positively with depth of tumor invasion (T status) (P = 0.016) and was associated with worse overall survival (P = 0.047). In patients without regional or distant lymph node metastasis (N0 or M0), EP2 overexpression was associated with worse overall survival (P = 0.033 and P = 0.003, respectively). Using Cox regression analysis, T status, N status, and M status were the independent factors of overall survival, but EP2 expression was not. However, when focusing on patients with T1-3N0M0 status, EP2 expression became an independent factor of overall survival (P = 0.048). Our results show that EP2 overexpression was associated with worse prognosis, and correlated positively with T status in ESCC. Meanwhile, among those patients at earlier stages, EP2 overexpression significantly disclosed patients at high risks for poor prognosis.