| Esophageal carcinoma (EC) is one of the six most common malignant diseases worldwide. The dramatic geographic distribution is the striking characteristic for EC, the ratios for EC incidence between the high- and low-risk areas could be as great as 500:1. Moreover, EC has a very poor prognosis; the five-year survival rate for the middle and advanced EC is only 10%. Linzhou (formerly Linxian) and Huixian of Henan Province, northern China, have been well recognized as the highest incidence areas for EC in the world. EC remains a leading cause of cancer-related deaths in these area. The reason for this stable incidence pattern are because of that: the exact etiological factors for EC have not been identified; the mechanism of esophageal carcinogenesis is not very clear; and there are lack of useful reagents for chemoprevention, sensitive biomarkers for early detection and high-risk subject screening.Studies by us and other laboratories indicate that an early indicator for the subjects predisposed to EC is the abnormal hyperproliferation of esophageal epithelial cells, morphologically manifested as basal cell hyperplasia (BCH), especially at the papilla region, dysplasia and cacinoma in situ, all these lesions could be considered as preacancerous lesions for EC. Our field work has showed that these lesions appear unstable, i.e., of the lesions with the similar morphology, some may progress to more severe type, or remain at that stage for long time, or return to less severe lesion, even to normal. These phenomena raise some important questions. For example, what are the key factors to address the mild lesions to more severe lesions? What is the mechanism to determine thereversibility of these lesions? Apparently, these questions could not be answered only by morphological analysis. To further characterize the molecular changes and their correlations with morphological alterations at the different stages of carcinogenesis may provide important clues to elucidate these questions: mass survey and follow-up studies to the population at high-incidence area for EC with linear interval biopsies could not be overemphasized in elucidating the natural history for EC, accumulating important biological material bank for molecular analysis and evaluating the effects of chemoprevention.The knowledge about the molecular alterations of esophageal carcinogenesis has been greatly improved in 1990s. The studies finished by ours and the other research groups showed that many important molecular alterations have occurred in the early stage of esophageal carcinogenesis, mainly including some tumor inhibition genes inactive, such as p53 mutation, Rb LOH, p14 and p15 loss, and some oncogene, such as Cyclin D1, C-myc, C-erbB2 active or overexpression. The molecular alterations may be the key mechanism to address the mild precancerous lesions into cancer. Most of the studies has focused on the cancer tissues but not the adjacent tissues, and there are few reports on molecular changes in both cancer tissue and adjacent tissue from the same EC patient. To further characterize the molecular changes in the multistage progress in esophageal carcinogenesis from the same patient, we designed this multi-profile and multi-molecular study focusing on the molecular events in cancer and adjacent tissue from the same EC patient.1 Materials and Methods1.1 Surgical and biopsy tissue collection and processingAll the surgically resected primary EC specimens were collected from 45 EC patients in Linzhou, Henan, the high incidence area for EC (30 men and 15 women, 36 to 75 years of age, with a mean ±SD of 57 37 ±8.34 years,) . All the patients had not received either chemotherapy or radiotherapy before surgery. All the specimens were confirmed by pathology as esophageal squamous cell carcinoma. Within one hour after excision, each specimen was cut into two segments, thecancer tissue and its adjacent tissue were collected as one case in one segment and stored in liquid nitrogen for further study The other segment was stain...
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