A review of the alterations in DNA methylation in esophageal squamous cell carcinoma

Epigenetic changes such as DNA methylation, histone modification, and loss of genome imprinting play a crucial role in esophageal squamous cell carcinogenesis, along with genomic and genetic alterations. DNA methylation is a fundamental epigenetic process that modulates gene expression. Cancer cells exhibit two types of alterations of DNA methylation: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. In several types of human cancers, the methods of detecting an aberrant methylation status have been applied to clinical fields to stratify high-risk groups, detect early cancer, and predict clinical outcomes. Importantly, epigenetic changes, including alterations in DNA methylation, are reversible and can thus be targets for cancer therapy or chemoprevention. Therefore, a better understanding of the DNA methylation in esophageal squamous cell carcinoma (ESCC) is important for optimizing cancer therapy and chemoprevention. We herein summarize the current knowledge regarding alterations in DNA methylation and the clinical implications in ESCC.     

长链非编码RNA HOTAIR 在食管鳞状细胞癌中的表达及其临床意义

【摘要】 目的 探讨长链非编码RNA HOTAIR在食管鳞状细胞癌组织中的表达情况及其临床意义。方法 采用原位杂交技术检测93例食管鳞癌组织及20例癌旁组织中HOTAIR的表达情况。运用SPSS16.0进行统计分析了解HOTAIR表达与临床病理特征之间的关系。结果 HOTAIR在食管鳞癌组织中比癌旁组织中表达阳性率高,且差异有统计学意义(P<0.001)。HOTAIR表达与食管鳞状细胞癌的浸润深度、临床分期、有无淋巴结转移、分化程度有关(P＜0.05),与年龄、性别无关(P＞0.05)。结论 HOTAIR与食管鳞癌的发生发展相关。     

Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma

BACKGROUND: Increased preoperative serum squamous cell carcinoma antigen (SCC-Ag) concentrations have been found to be associated with advanced stage and poor prognosis in lung and cervical cancers. Because little was known about the significance of SCC-Ag concentration in patients with esophageal cancer, the aim of this study was to analyze the clinicopathologic significance of SCC-Ag in patients with esophageal SCC. PATIENTS AND METHODS. Preoperative SCC-Ag concentration was measured with enzyme-linked immunosorbent assay in 309 patients with primary esophageal SCC. All patients underwent curative radical surgery without any preoperative therapy. In 215 of 309 patients, carcinoembryonic antigen (CEA) was also measured to compare clinical significance of CEA with that of SCC-Ag. The prognostic significance for survival of SCC-Ag concentrations was studied with multivariate analysis with Cox proportional hazards model. RESULTS: The SCC-Ag concentration and the positivity rate of SCC-Ag were significantly elevated in patients associated with tumor progression. Statistically significant differences in SCC-Ag concentrations and SCC-Ag positivity rates were observed depending on tumor size, tumor depth, lymph node status, and distant metastasis. Although CEA was not a prognostic factor (P =.21), a high SCC-Ag concentration was a significant prognostic factor (P <.01). Multivariate analyses indicated that T factor had the best predictive power, but SCC-Ag concentration contained additional, independent prognostic information. CONCLUSION: Our findings suggest that preoperative serum SCC-Ag concentrations might provide a predictive information for tumor progression and survival in patients with esophageal SCC.     

Lesser curvature lymph node metastases with esophageal squamous cell carcinoma: implications for gastroplasty

The creation of a gastric tube after subtotal esophagectomy includes resection of the lesser curvature and abdominal lymph nodes. The fundus rotation gastroplasty has been recently proposed as an alternative technique of reconstruction that preserves the vascular arcade of the lesser curvature. This study investigates the number of resected and metastatic lymph nodes associated with abdominal lymphadenectomy to assess the oncologic radicality of fundus rotation gastroplasty. In this prospective clinical trial a two-field lymphadenectomy was performed in 39 patients with squamous cell carcinoma of the esophagus. The abdominal lymphadenectomy included partial resection of compartment I (lymph node groups 1, 2, and 3) and compartment II (lymph node groups 7, 8, 9, and 11). A meticulous workup of the specimen allowed an exact classification of specific lymph node groups and their metastatic status. After two-field lymphadenectomy a total of 1170 lymph nodes (average 30.0) including 690 abdominal lymph nodes with an average of 17.7 per patient were resected. Metastatic disease was found in 27 of 39 patients (pN1 69.2%), with metastatic growth in 116 of 867 resected lymph nodes (13.4%). Of the 27 pN1 patients, 21 had abdominal lymph node metastases. Metastatic lymph nodes at the lesser curvature (groups 1, 3, and 7) were detected in 11.7%, 16.7%, and 29.7% of the resected lymph nodes, respectively. Of the 21 patients (85.7%) with abdominal lymph node metastases, 18 had positive lymph nodes at the lesser curvature. Squamous cell carcinoma of the esophagus is associated with a high rate of lymph node metastases at the lesser curvature and the left gastric artery. Therefore preservation of the lesser curvature and the left gastric artery for gastroplasty reduces the radicality regarding lymph node metastases.     

RhoE与EGFR在食管鳞癌中表达的研究

目的：探讨RhoE与EGFR在食管鳞状细胞癌中的表达及其关联性,并分析其临床意义。方法运用快捷免疫组化方法对我院2011年1月至2012年1月收集的食管鳞状细胞癌癌组织及相应的癌旁组织59例进行检测,测定RhoE与EGFR的表达情况,运用统计学方法结合患者其他指标进行分析。结果①食管鳞癌癌旁正常组织中RhoE蛋白的阳性表达灰度值是52．131±3．682,食管鳞癌组织中为37．115±4．314,二者差异有统计学意义（P＜0．001）。②食管鳞癌癌旁正常组织中EGFR蛋白的阳性表达灰度值是33．956±3．716,食管鳞癌组织中为48．168±2．945,二者差异有统计学意义（P＜0．05）。③二者表达水平情况与肿瘤的临床分期、分化程度、淋巴转移以及有无浸润都有密切关系（P＜0．001）,与肿瘤的大体分型、大小和部位无关（P＞0．05）。④RhoE与EGFR在食管鳞癌组织中的表达呈负相关（P＜0．01）。结论 EGFR基因的表达水平在食管鳞癌中是增高的,而RhoE则是降低的;并且二者呈负相关,与肿瘤的分化程度、有无浸润、淋巴的转移以及临床分期等密切相关,这提示着EGFR的高表达或许参与了肿瘤的发生与发展,对二者的表达情况进行检测有助于我们了解食管癌的生物学行为以及评估预后。     

Distinctive clinicopathological characteristics in esophageal squamous cell carcinoma.

Esophageal cancer is an aggressive disease with a generally poor prognosis. Frequently, patients present late with obstructive symptoms indicating advanced tumors. Therefore, serial histopathological investigations of esophageal cancer are now being performed more extensively, and several distinctive clinicopathological features have been demonstrated. In this review, we present some of the distinctive features of esophageal cancer and discuss their clinicopathological significance. These characteristics include: (1) the frequent presence of lymph node metastasis, (2) the morphological features and depth of tumor invasion, (3) the synchronous and metachronous occurrence of carcinoma of other organs, (4) the frequent coexistence of squamous epithelial dysplasia, (5) the frequent coexistence of intraepithelial spread, blood vessel, and lymphatic permeation, (6) the occasional existence of intramural metastasis, (7) the frequent coexistence of multiple primary carcinomas, and (8) the occasional coexistence of glandular differentiation with squamous cell carcinoma.     

Detection of telomerase activity in esophageal squamous cell carcinoma and normal esophageal epithelium

Background/aims: Relatively little has been reported about the telomerase activity of esophageal squamous cell carcinoma or normal esophageal epithelium. In this study, we have evaluated whether telomerase activity is a useful marker for detecting malignancies in the esophagus. Patients/methods: Esophageal carcinomas and normal esophageal tissues adjacent to carcinomas were obtained from 52 surgically treated, unselected patients, and normal esophageal epithelium from 11 non-cancerous patients were obtained by means of biopsy. The telomeric repeat amplification protocol (TRAP) assay was used for detection of telomerase activity in these samples. The incidence of detection of telomerase activity in esophageal carcinoma was compared with that of telomerase activity in normal esophageal epithelium. Moreover, the clinicopathological characteristics of telomerase-positive tumors were compared with those of telomerase-negative tumors. Results: Of the 52 carcinomas, 40 (77%) had detectable telomerase activity. However, telomerase activity was detected in 45 of 52 (87%) normal tissue samples adjacent to carcinomas and in 8 of 11 (73%) normal esophageal epithelium from non-cancerous patients. In esophageal cancer, no significant difference was detected in the clinicopathological findings between the telomerase-positive and -negative cases. Conclusion: These results indicate that not only esophageal squamous cell carcinomas but also normal esophageal epithelium show strong telomerase activity. Thus, telomerase activity may not be a good marker for the detection of carcinoma in the esophagus. Received: 16 March 1999 Accepted: 8 July 1999     

Outcome of histologically node-negative esophageal squamous cell carcinoma

The outcome of node-negative esophageal carcinoma and the prognostic significance of lymph node micrometastasis remain unknown. The aim of this retrospective study was to clarify these two points. A series of 98 patients who underwent curative operation for histologically node-negative (pN0 in TNM classification) esophageal carcinoma were enrolled in the study. We reviewed the cause of death of these patients. The survival curves were calculated and compared after stratifications according to clinicopathologic parameters. Lymph node micrometastasis in the patients with recurrences was examined using immunohistochemical staining of cytokeratin. Their ages ranged from 45 to 83 years (mean 64.3 years). There were 83 men and 15 women. Altogether, 54 patients were still alive, and 44 had died. A total of 9 patients died from recurrence of their esophageal carcinoma, 33 died from other causes (pneumonia 11, extraesophageal carcinoma 7, and so on), and 2 died from unknown causes. Eight patients had locoregional recurrences, and two patients had distant recurrences. The overall survival rate for the 98 patients was 58.2%. The survival for patients with pT2 or pT3 tumors was significantly worse than for those with pTis or pT1 tumors (p = 0.02, log-rank test). Other clinicopathologic factors did not affect the prognosis. Immunohistochemical study found no lymph node micrometastasis in 365 lymph nodes resected from the patients with recurrences. Only the depth of tumor invasion affected the outcome of patients with node-negative esophageal carcinoma. Altogether, 75% of patients died of other causes without recurrence, with the two main causes of death being pulmonary complications and extraesophageal carcinoma in these patients. Lymph node micrometastasis was not associated with recurrence in this series.     

Postoperative therapy of recurrent esophageal squamous cell carcinoma

Some 218 resected cases and 43 autopsied cases after resection during the last 13 years were analyzed with regard to the mode of recurrence and survival. Several factors were investigated with the following results. 1) Extensive clearance of upper mediastinal lymph nodes during radical surgery may reduce the incidence of tumor recurrence. It is preferable to remove the cervical lymph node, however, after positive metastasis to cervical lymph node. 2) Beginning in 1981, interstitial brachytherapy of 192Ir seed assemblies using afterloading techniques was administered to two patients with esophageal carcinoma infiltrating the aorta and four patients infiltrating the trachea and main bronchus which were not completely resected in either case due to invasion of adjacent organs. No significant difference in life-prolongation was observed, but it may have been effective for prevention of localized recurrence in cases with aortic infiltration and with infiltration of the trachea and bronchus. 3) From 1984, eleven patients with recurrent squamous cell esophageal carcinoma were treated with combination chemotherapy sandwiched with irradiation (CDDP/5FU-RT-CDDP/5FU). Eight patients (73%) had complete or partial response, and six patients survived over one year after combination chemotherapy sandwiched with irradiation. Combination chemotherapy sandwiched with irradiation appears to be effective in the treatment of patients with recurrent squamous cell carcinoma of the esophagus. Toxic effects are moderate and manageable.     

STAT3在食管鳞状细胞癌中的表达和意义

目的研究STAT3蛋白表达与食管鳞状细胞癌临床病理特征的关系,探讨其在食管癌变中的可能作用。方法应用免疫组织化学S-P法检测60例食管鳞状细胞癌及其癌旁组织中STAT3蛋白的表达,结合临床资料进行分析。结果STAT3蛋白阳性反应主要定位于胞质。食管鳞状细胞癌组织中STAT3蛋白表达阳性率86.7%(平均灰度值为36.05±13.74)明显高于正常组织阳性率17.6%(平均灰度值为16.92±5.43)(P<0.05)。STAT3蛋白在低分化、中分化、高分化鳞癌组的阳性表达率分别是100%、95%、73.08%,平均灰度值分别是51.22±7.09、42.18±7.21、23.16±6.94,3组间差异有统计学意义(P<0.01)。肿瘤分化程度越高STAT3蛋白表达越低。有淋巴细胞转移的食管癌组织中STAT3表达的阳性率100%(平均灰度值45.36±10.36),明显高于无淋巴细胞转移的食管癌组织阳性率78.38%(平均灰度值30.26±12.41)(P<0.05)。结论STAT3蛋白在食管鳞状细胞癌组织中的高表达可能与食管鳞癌的发生有关系。     

Clinicopathologic characteristics of esophageal squamous cell carcinoma in younger patients

Background. The aim of the current study was to find out the clinicopathologic characteristics of younger patients with squamous cell carcinoma of the esophagus.

Methods. A total of 259 patients with esophageal squamous cell carcinoma who had been treated by esophagectomy and reconstruction within 10 years between January 1990 and December 1999 were studied. Clinicopathologic characteristics were compared between 27 patients younger than 50 years and 232 patients 50 years and older.

Results. A significant difference was observed with regard to the size of the tumor (6.3 ± 3.8 cm in younger patients versus 5.0 ± 2.4 cm in older patients; p = 0.017). The proportion of patients with TNM stage III or IV in younger patients (59.3%, 16 of 27) was significantly higher than that in older patients (38.3%, 89 of 232; p = 0.020). Nevertheless, no significant difference in the 1-, 3-, and 5-year survival rates was observed between younger patients (77.2%, 54.7%, and 54.7%, respectively) and older patients (81.9%, 54.2%, and 48.8%, respectively).

Conclusions. Although the prognosis of younger patients with esophageal squamous cell carcinoma did not differ from that of older patients, esophageal squamous cell carcinoma in younger patients has more malignant potential and aggressive activity.     

早期和浅表性食管鳞状细胞癌内镜治疗现状

食管癌目前已成为我国主要恶性肿瘤之一,其发病率和病死率逐年增加,发病原因多而复杂。早期食管鳞状细胞癌是指局限于食管黏膜层的鳞状细胞癌,而侵犯到黏膜下层的鳞状细胞癌属于浅表性食管癌。随着内镜检查的普及和技术的进步,早期和浅表性食管鳞状细胞癌的诊断率不断提高,目前内镜下治疗的方法主要有内镜下切除和非切除治疗,其中内镜下切除治疗主要有内镜下黏膜切除术、内镜下黏膜剥离术等,相对于手术治疗,内镜下切除治疗具有安全、创伤小、操作简单、并发症少等优点,提高了患者的生存质量。但对于淋巴结转移风险较大的患者,若行内镜下治疗后,建议术后密切随访。随着针对较大病变的内镜下隧道式黏膜下剥离术等技术的开展,内镜下治疗将会为早期食管肿瘤的患者提供更好的治疗方案。