Prognostic Factor In Esophageal Cancer Research Articles

Expression of the eukaryotic translation initiation factor 4E (eIF4E) and 4E-BP1 in esophageal cancer

Objectives: The eukaryotic initiation factor 4E (eIF4E) has been shown to play a key role in cell growth, and several studies have documented an increased expression of eIF4E in a number of solid tumors, including breast, bladder, cervical and head and neck cancers. The aim of this study was to determine the level of expression of eIF4E and eIF4E-binding protein 1 (4E-BP1) in esophageal cancer. Design and methods: Tumor and normal adjacent tissue samples (as controls) were obtained from 99 patients with esophageal cancer. eIF4E and 4E-BP1 levels were determined by using Western blot analysis. eIF4E was purified by affinity chromatography using m 7GTP-sepharose, and the levels of 4E-BP1 bound to eIF4E were determined. Results: In cancerous esophageal tissues, eIF4E level was elevated by a mean of 12.59 ± 1.66-fold, and 4E-BP1 was elevated by a mean of 15.76 ± 2.45-fold when compared to normal adjacent tissues. Both eIF4E and 4E-BP1 expressions were higher in cancerous compared to noncancerous esophageal tissues. Conclusions: A higher expression of eIF4E was correlated with advanced stages. The inverse relationship found between the increases in 4E-BP1 levels observed in esophagus tumors and lymph node involvement would support the hypothesis that the overexpression of eIF4E can be involved in tumorigenesis and a possible role of 4E-BP1 as a prognostic factor in esophageal cancer.

Multiple management modalities in esophageal cancer: epidemiology, presentation and progression, work-up, and surgical approaches.

Annually, approximately 13,200 people in the U.S. are diagnosed with esophageal cancer and 12,500 die of this malignancy. Of new cases, 9,900 occur in men and 3,300 occur in women. In part I of this two-part series, we explore the epidemiology, presentation and progression, work-up, and surgical approaches for esophageal cancer. In the 1960s, squamous cell cancers made up greater than 90% of all esophageal tumors. The incidence of esophageal adenocarcinomas has risen considerably over the past two decades, such that they are now more prevalent than squamous cell cancer in the western hemisphere. Despite advances in therapeutic modalities for this disease, half the patients are incurable at presentation, and overall survival after diagnosis is grim. Evolving knowledge regarding the etiology of esophageal carcinoma may lead to better preventive methods and treatment options for early stage superficial cancers of the esophagus. The use of endoscopic ultrasound and the developing role of positron emission tomography have led to better diagnostic accuracy in this disease. For years, the standard of care for esophageal cancer has been surgery; there are several variants of the surgical approach. We will discuss combined modality approaches in part II of this series.

Expression of Vascular Endothelial Growth Factor as a Prognostic Factor in Node‐positive Squamous Cell Carcinoma in the Thoracic Esophagus: Long‐term Follow‐up Study

To clarify the clinical significance of the expression of vascular endothelial growth factor (VEGF) in squamous cell carcinoma in the thoracic esophagus, particularly as a prognostic factor, we have investigated the correlation between VEGF expression in tumor cells and microvessel density (MVD), pathologic factors, and survival. A total of 92 specimens, each from a thoracic esophageal squamous cell cancer patient who underwent transthoracic curative R0 esophagectomy between 1991 and 1994, were examined immunohistochemically using anti-human VEGF and anti-human von Willebrand factor antibodies. The incidence of VEGF expression in the tumor cells was relatively low, at 23.9% of all specimens. There was no significant correlation between VEGF expression and histopathologic factors. The MVD at the tumor margin in patients with VEGF-positive tumor cells was significantly greater than that in VEGF-negative cases (35.2 +/- 8.9 vs. 22.7 +/- 8.2). The survival rate for patients with VEGF expression was significantly lower than that of those without VEGF expression; the same situation was found in node-positive patients but not in node-negative patients. In addition, multivariate analysis revealed that VEGF expression was an independent prognostic factor in node-positive patients. VEGF may be implicated in the definition of the malignant phenotype of squamous cell esophageal cancer via tumor angiogenesis. Accordingly, VEGF expression in the tumor cells could be a useful prognostic factor for esophageal cancer, particularly in node-positive patients.

Cell cycle-regulated factors in esophageal cancer.

Alterations of cell cycle-regulated genes play an important role in the process of carcinogenesis, and some of them are thought to be prognostic factors in esophageal cancer. The expressions of p53, p16, pRB and Cyclin D1 proteins were evaluated immunohistochemically in 144 patients who underwent curative esophagectomy without any adjuvant therapy before surgery. p53 overexpression was observed in 99 (69%) out of the 144 patients. No significant correlation was noted between p53 and any other gene expression. p16 expression was observed in 12 (8.3%) out of all cases. A negative correlation was recognized between p16 and Cyclin D1 expression (P=0.0004). pRB expression was observed in 130 (90.3%) out of all cases, whereas pRB expression was not observed in 11 out of the 12 patients with p16-positive tumors. A negative correlation was also found between p16 and pRB (P < 0.0001). A positive correlation was noted between pRB and Cyclin D1 expression (P=0.0009). The cumulative survival rate of patients without pRB expression was significantly lower than that of patients with positive expression (P=0.003). In the multivariate survival analysis, pRB expression was an independent prognostic factor. In 98% of all patients with esophageal cancer, impairment of the G1 checkpoint is due to a loss of function by p16, pRB or Cyclin D1, which showed a negative correlation in each factor. In addition, aberrant expression of pRB is useful as a prognostic factor in esophageal cancer.

VEGF-C expression correlates with histological differentiation and metastasis in squamous cell carcinoma of the esophagus

Vascular endothelial growth factor C (VEGF-C) is known to act in lymphangiogenesis. Recent reports suggest VEGF-C plays a role in the spread of several cancers to the lymph system. Lymphatic spread is a critical prognostic factor in esophageal cancer, however, the molecular mechanism involved in the spread of cancerous cells remains unclear. In the present study the clinicopathological implication of VEGF-C was analyzed using immunohistochemistry. Seventy-one patients with esophageal squamous cell carcinoma (ESCC) resected in our institute were included in this study. Formalin-fixed paraffin-embedded specimens were stained for VEGF-C and the correlation between the staining, its clinicopathological parameters and its prognostic power were analyzed statistically. Only histological grade (differentiation) was shown to have a statistically significant correlation with VEGF-C expression (p=0.028). Age (p=0.064), lymph node metastasis (pN) (p=0.085) and vascular invasion (p=0.092) tended to correlate with VEGF-C expression although on analysis this correlation was not statistically significant. The results suggested there is no prognostic implication for VEGF-C in ESCC (p=0.80). There is no significant correlation between VEGF-C expression and clinicopathological parameters involved in lymphatic spread. However, VEGF-C expression might play an important role in metastasis of ESCC since histological grade was closely related to lymph node metastasis and distant metastasis.

An evaluation of malignancy and prognostic factors based on mode of lymph node metastasis in esophageal carcinoma.

This study was conducted to evaluate lymph node metastasis as a key prognostic factor in esophageal cancer. Metastatic lesions in lymph nodes were grouped by histological morphology as intracapsular or extracapsular, and the significance of lymph node metastasis was evaluated by relating metastatic lesions to clinical pathologic factors and patient prognosis. In our hospital, 46 of 81 patients who underwent resection of esophageal cancer developed lymph node metastasis. These 46 patients were enrolled in a study analyzing the relationship between the metastatic mode and the clinicopathological factors. The frequency of extracapsular metastasis was significantly high in patients with a profound depth of cancer, three or more metastases, distant metastasis (n3 and n4), or severe lymphatic invasion. The prognosis was significantly worse in patients with extracapsular metastasis, and this tendency was also seen even in patients with three or more metastases, limited metastasis (n1 and n2), or mild lymphatic invasion (ly0 and ly1). These findings suggest that the metastatic mode reflects the degree of esophageal cancer progression and is an important prognostic factor.

Prognostic Factors in Esophageal Cancer

Clinical and pathologic factors relevant to the prognosis of esophageal cancer are reviewed in this article. Clinical factors discussed include endoscopic, radiologic, and surgical findings. The importance of Barrett's esophagus and the role of endoscopic screening in the diagnosis of dysplasia and the prevention of adenocarcinoma are evaluated. Pathologic factors include the traditional ones of tumor type, stage, and grade as well as newer tumor markers related to DNA content, rate of cell proliferation, oncogenes, and tumor suppressor genes.

Overexpression of metallothionein correlates with chemoresistance to cisplatin and prognosis in esophageal cancer.

The aim of this study was to determine the correlation of metallothionein (MT) expression with resistance to cisplatin and to identify prognostic factors in esophageal cancer. Immunostaining for MT was performed on the specimens of squamous cell carcinoma of the esophagus resected from 68 patients with curative intent. The expression of MT was evaluated in terms of clinicopathologic variables, effect of cisplatin, and the patients' survival. Overexpression of MT in the tumor was found in 70.6% of the patients. Stage III and IV tumors were more common in MT-positive tumors (p = 0.0282) but there was no difference in other clinicopathologic variables between MT-positive and MT-negative groups. Stage, cisplatin therapy, and tumor length were the independent prognostic indicators by multivariate analysis. Among 43 patients treated with cisplatin, the 5-year survival rate was 56% for MT-negative and 26% for MT-positive patients (p = 0.0277). In the MT-negative patients, multivariate analysis revealed that curability, stage, cisplatin therapy, and tumor length were the independent prognostic factors. These findings suggest that MT expression in squamous cell carcinoma of the esophagus is a major determinant of the chemoresistance to cisplatin and may be a predictor of poor prognosis.