| 1 BACKGROUND AND OBJECTIVELinzhou of Henan province,northern China,has been recognized as the highest incidence area for esophageal cancer in the world,and the predominant histological type in this area is squamous cell carcinoma(ESCC).The incidence of gastric cardic adenocarcinoma(GCA) is also very high in this area.At present,ESCC and GCA are the most common malignant diseases in Linzhou,Henan province,and remain the leading cause of cancer-related deaths in these areas.The other phenomenon in Linzhou is that the primary ESCC and GCA could occur together on the same patient, which has been named as concurrent carcinoma(CC) of the esophagus and gastric cardia.CC is not uncommon in this area.Because most of the CC patients are misdiagnosed,reports about the incidence of CC are different from 0.4 to 2.5 percents. The previous study found that prevalence of primary concurrent cancers of the esophagus and gastric cardia from the same patient(CC) is 7 percents in this area.The high coincident alterations for many kinds of proteins in ESCC and GCA from the same patient indicate the possibility of similar molecular basis,which provides important molecular basis and etiological clue for similar geographic distribution and risk factors in ESCC and GCA.Epithelial dysplasia is severe precancerous lesions of esophagus and gastric cardia cancer.The literature for the concurrent dysplasia of esophagus and gastric cardia(cDYS) from the same patient is very few.Genetic background and environmental factors of cDYS are similar and comparability,so CC/cDYS is very ideal model for discriminating differences of ESCC and GCA.It is apparent that to further characterize the molecular changes of cDYS patients may provide not only more information on the molecular mechanism and also the etiological clues for ESCC and GCA.To further characterize the prevalence and molecular mechanisms for cDYS,the present study was undertaken to retrospectively analyze the clinical data from 32521 patients with either ESCC or GCA and esophageal/gastric cardia biopsies from the 4315 symptom-free subjects at the high-incidence area in Henan,northern China.Histopathological reexaminations were performed on 3750 cases with GCA and ESCC at the lower segment of the esophagus. Immunohistochemistry(ABC) method was applied to 30 cDYS samples to characterize the alternations of Rb and Bax.2 MATERIALS AND METHODSTo determine the prevalence of cDYS by gender and age,recorded clinical data from 32521 patients with either ESCC or GCA from the high-incidence area in Henan over 35 years(1974-2008) were analyzed.4315 esophageal/gastric cardia biopsies from the symptom-free subjects examined by endoscopy were collected from high risk area in Henan for histopathological analysis.3119 cases with GCA and 516 with ESCC at the lower segment of the esophagus were enrolled in this study from Linzhou,the high-incidence area for ESCC.All the patients were confirmed by histopathological diagnosis.Surgically resected specimen were collected 1-2 hours after operation,all the resected tissues were fixed with alcohol,paraffin embedded and partial serially sectioned for histopathological diagnosis.Rb and Bax protein expressions were detected by the immunohistochemical method(ABC) in 30 patients with both eDYS and gDYS from the high incidence area for esophageal cancer in Henan,including 24 males and 6 females with a mean age of 59±7.All the patients were not treated by either chemotherapy or radiotherapy before operation.All the resected tissues were fixed with alcohol,paraffin embedded and partial serially sectioned for histopathological diagnosis and immunostaining.x~2 Test,Spearman correlation test,Fisher's exact test and Kappa test were applied for the statistics(P＜0.05 was considered significant).3 RESULTS3.1 Prevalence of GCA,ESCC,CCThere were 32521 cases with ESCC and GCA enrolled in this study from Linzhou area over years 1974-2008.Of the 32521 cases,there were 21066 cases with ESCC(65%),11030 cases with GCA(34%) and 425 cases with CC(1.3%).The prevalence of ESCC,GCA and CC in males was higher than that in females;the ratio of male and female in ESCC,GCA,CC is 1.6:1,3.3:1,4.8:1,respectively.The sex-related rate of GCA and CC was higher than that of ESCC,and especially that of CC was the highest in the three(P＜0.01).ESCC,GCA and CC occurred more frequently in the group of age 50-69(74%)(Aged 50-59 and 60-69 account for 40%, 34%.).There was no significant difference by gender and ages,respectively(P＞0.05).3.2 Prevalence of eDYS,gDYS,cDYS683 cases with cDYS(683/3750,18.2%) were identified from the adjacent tissue of 3750 surgically resected specimens with ESCC and GCA.Of the 3750 cases,there were 391 cases with eDYS(391/516,75.8%) and 113 cases with gDYS(113/516, 21.9%) in ESCC;there were 700 cases with eDYS(700/3119,22.4%) and 1915 cases with gDYS(1915/3119,61.4%) in GCA;there were 73 cases with eDYS(73/115, 63.5%) and 43 cases with gDYS(43/115,37.4%) in CC.Of the 4315 symptom-free subjects examined by endoscopy,206 cases were observed with eDYS(206/4315, 4.8%),229 cases with gDYS(229/4315,5.3%) and 29 cases with cDYS(29/4315, 0.7%). The detection rate of eDYS in the tissue adjacent to ESCC(75.8%) was higher than that in the tissue adjacent to GCA(22.4%)(P＜0.05);the detection rate of gDYS in the tissue adjacent to GCA(61.4%) was higher than that in the tissue adjacent to ESCC(21.9%)(P＜0.05);the prevalence of cDYS was similar between the tissue adjacent to ESCC and GCA(19.6%vs 17.6%,P＞0.05),but was lower than that in the tissue adjacent to CC(29.6%)(P＜0.05);the detection rate of cDYS in surgically resected specimens was apparently higher than that in biopsy tissues from the symptom-free subjects(18.2%vs 0.7%,27 folds,P＜0.05);in ESCC,the prevalence of cDYS with 40-49 years old in males was higher than that in females(P＜0.05);in GCA,the prevalence of gDYS in the groups of age 30-39 and over 70 in males was higher than that in females(P＜0.05),but the detection rate of eDYS,gDYS and cDYS with 50-59 years old was lower than that in females(P＜0.05);there was no significant difference by gender and ages in the rest part(P＞0.05).The high-incidence age of cDYS in the surgical specimens was 50-69 years;that in the symptom-free subjects was 40-59 years;the former was higher than the latter(P＜0.05).3.3 Immnnohistochemical analysis for Rb and Bax expression in cDYSHistopathologically,all the 30 cases were confirmed with both eDYS and gDYS. The positive immunohistochemical staining for Rb was observed in cell nucleus from yellow to brown,and Bax was observed in cell nucleus or cytoplasm.The positive rates of Rb in eDYS and gDYS were 70%(21/30) and 41%(24/30),and the difference was no significant(P＞0.05).However,there were 25 patients with Rb coincident changes in eDYS and gDYS from the same patient in 30 patients with cDYS(83%,25/30).The positive coincidence rate for Rb positive expression in eDYS and gDYS from the same patient accounted for 67%(20/30) and the negative coincidence rate was 17%(5/30)(Kappa=0.561,P＜0.05).The significant relationship between Rb coincidence expression in eDYS and gDYS was found(P＜0.05).The positive rates of Bax in eDYS and gDYS were 73%(22/30) and 60% (18/30),and the difference was no significant(P＞0.05).However,there were 22 patients with Bax coincident changes in eDYS and gDYS from the same patient in 30 patients with cDYS(73%,22/30).The positive coincidence rate for Bax positive expression in eDYS and gDYS from the same patient accounted for 53%(16/30) and the negative coincidence rate was 20%(6/30)(Kappa=0.412,P＜0.05).The significant relationship between Bax coincidence expression in eDYS and gDYS was found(P＜0.05).4 CONCLUSIONS4.1 The cases with ESCC accounted for 65%,the cases with GCA accounted for 34%, and the cases with CC accounted for 1.3%at high-incidence area in Henan.The prevalence of ESCC and GCA in males was higher than that in females;the ratio of male and female in ESCC,GCA and CC was 1.6:1,3.3:1,4.8:1,respectively.The cases with cDYS in the tissue adjacent to ESCC and GCA accounted for 18.2%, which was higher than that from the symptom-free subjects,suggesting that cDYS was a common pathological change and was the important histological basis for concurrent esophageal and gastric cardia carcinogenesis.The present results provide important evidence for field carcinogenesis.4.2 This study demonstrates that ESCC,GCA and CC occurred more frequently in the group of age 50-69(74%)(Aged 50-59 and 60-69 accounted for 40%,34%, respectively.),cDYS occurred more frequently in the group of age 40-59,while eDYS and gDYS occurred more frequently in the group of age 50-69.4.3 The prevalence of cDYS in surgically resected specimens was apparently higher than that in biopsy tissues from the symptom-free subjects(18.2%vs 0.7%). Obviously,the small area of diagnosis and different sampling method might cause missed diagnosis of a part of cDYS;younger age of the symptom-free subjects and short time exposure to carcinogenic factors might lead to the low prevalence of cDYS in the symptom-free subjects.4.4 The high incidence age of cDYS in biopsy tissues from the symptom-free subjects was ten years lower than that in surgically resected specimens.The present result demonstrates that environmental carcinogenic factors have a long-accumulated effect on esophageal epithelial so as to abnormal proliferation of epithelial cells.Meanwhile, length of accumulative action has an apparent influence on the occurrence of pathological changes.Furthermore,the whole esophageal epithelial by exposure to carcinogenic factors may cause field carcinogenesis of epithelial.The above-metioned is just theoretical basis of cDYS and CC development.4.5 The prevalence of eDYS in ESCC at the lower segment of the esophagus was significantly higher than that in the tissue adjacent to GCA.However,the prevalence of gDYS in the tissue adjacent to GCA was significantly higher than that in ESCC at the lower segment of the esophagus.This result further suggests that DYS might be one of the important precancerous lesions for ESCC/GCA,and multistage carcinogenesis theory of DYS towards cancer.4.6 The high coincident alterations for Rb and Bax in eDYS and gDYS from the same patient indicate that there may be similar risk factors and molecular mechanisms involved in ESCC and GCA,which provides important etiological clue for similar geographic distribution and risk factors in ESCC and GCA. |
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