Adenocarcinoma arising in Barrett's oesophagus: evidence for the participation of p53 dysfunction in the dysplasia/carcinoma sequence.

Adenocarcinoma arising in Barrett's oesophagus is often preceded by mucosal dysplasia, but little is currently known about the aetiology or natural history of this dysplasia/carcinoma sequence. To investigate the participation of the tumour suppressor gene p53 in this sequence, an immunohistochemical analysis of p53 protein overexpression, which is known to closely correlate with point mutation of the p53 gene, was conducted in 30 patients with Barrett's adenocarcinoma. Adjacent Barrett's mucosa was dysplastic in 21 (70%) patients. Sixteen (53%) tumours overexpressed p53, 10 of which had adjacent dysplastic Barrett's mucosa. In all 10 patients, this dysplastic mucosa also overexpressed p53, predominantly in areas of high grade compared with low grade dysplasia. In contrast, none of the dysplastic mucosa adjacent to 11 tumours lacking p53 overexpression showed detectable values of p53. These results suggest that p53 dysfunction may participate in the progression from dysplasia to carcinoma in some patients with Barrett's oesophagus.     

p53 is an indicator of tumor progression in early but not advanced gastric carcinomas

BACKGROUND/AIMS: p53 plays an important role in the development of gastric carcinomas through its effect on apoptosis. Its use as a biomarker of tumorigenesis and progression in clinical tissue is currently under consideration. This project assessed its value in early and advanced stage gastric carcinomas. METHODOLOGY: The characteristics of positive staining for p53 was evaluated in 202 gastric adenocarcinomas classified into early stage (T1) (127 cases) and advanced stage (T2, 3 and 4) (75 cases) using the tumor-node-metastasis classification. Four subgroups (classified as p53 negative, +, ++ and +++ according to the level of positivity) were investigated for relationships with apoptosis (morphology) or cell proliferation (Ki-67). RESULTS: The mucosa of early stage and both mucosa and subserosa of advanced cancers were examined. p53-positive early stage cancers had more apoptosis but also more proliferation than p53-negatives (P<0.05), perhaps indicating conferral of a growth advantage. In advanced cancers, there was no correlation between apoptosis and extent of p53 positivity. p53 positivity had no correlation with cell proliferation in the mucosa and subserosa of these cancers. CONCLUSIONS: p53 may be useful as an indicator of development and progression in early stage gastric cancers but this is not the case for advanced stage gastric cancers.     

Tumour size is related to the curability of signet ring cell early gastric cancer with endoscopic submucosal dissection: A retrospective single centre study

Background

Endoscopic submucosal dissection is applied in selected cases of signet ring cell early gastric cancer. However, factors related to curability of signet ring cell early gastric cancer with this method have not been fully evaluated. Our aim was to evaluate factors related to incomplete resection in signet ring cell early gastric cancer with endoscopic submucosal dissection.

Methods

A retrospective analysis was performed on a total of 126 consecutive patients with signet ring cell early gastric cancer who had undergone endoscopic submucosal dissection at the Severance Hospital in Korea, between March 2007 and March 2012. The clinical outcomes were reviewed and factors related to incomplete resection were analysed.

Results

Multivariate analysis showed that large tumour size was the only significant factor related to incomplete resection (P = 0.006; hazard ratio, 1.040; 95% confidence interval, 1.101–1.084). In addition, large tumour size was the only significant factor related to endoscopic size underestimation (P < 0.001; hazard ratio, 1.391; 95% confidence interval, 1.221–1.586). The rate of endoscopic size underestimation was significantly higher in tumours with a size ≥20 mm (P < 0.001).

Conclusions

To improve the curability of signet ring cell early gastric cancer with endoscopic submucosal dissection, larger tumours (especially tumour with a size ≥20 mm) should be resected with a larger margin.     

BSG President's Report for 1994-5

p53 Protein accumulation in early gastric carcinoma was studied in relation to the histological type (Lauren classification) and the type of growth pattern, including the chronology of p53 protein accumulation during carcinogenesis. Forty five, paraffin embedded gastrectomy specimens from early carcinomas were examined for the presence of chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type and the type of growth pattern were reassessed for all early carcinomas. p53 Protein accumulation was examined using the monoclonal antibody DO-7. Complete absence of p53 protein accumulation was observed in normal gastric mucosa, chronic atrophic gastritis, and intestinal metaplasia, irrespective of subtype. In gastric dysplasia (one mild, two moderate, and one severe), only severe dysplasia was p53 positive. Intestinal type (n = 20) and diffuse type early gastric carcinomas (n = 25) were p53 positive in 70% and 52% of cases, respectively. Both tumour types differed significantly in the percentage of p53 positive tumour cells per tumour (p < 0.01) and in staining intensity (p < 0.05). No significant difference in p53 protein accumulation was found between early carcinomas with different types of growth pattern. It is concluded that p53 protein accumulation--usually reflecting missense p53 gene mutation--seems to be a late event in gastric carcinogenesis. Moreover, it is suggested that missense p53 gene mutation occurs in a final pathway common to both intestinal and diffuse type of early gastric carcinoma. Finally, the types of growth pattern do not seem to differ in p53 protein accumulation.     

Epithelial cell turnover, p53 and bcl-2 protein expression during oncogenesis of early and advanced gastric cancer in a Western population

OBJECTIVES: To investigate epithelial cell turnover alterations, and p53, bcl-2 protein expression during development of early and advanced gastric cancer in a Western population. METHODS: We investigated cell apoptosis and proliferation rates, p53 and bcl-2 protein expression in 17 early and 34 advanced gastric carcinomas and in the adjacent non-dysplastic mucosa. Cell proliferation, p53 and bcl-2 expression were detected immunohistochemically using MIB-1, anti-p53 and anti-bcl-2 monoclonal antibodies. Apoptosis was measured by TUNEL. The rate of the positive stained cells (labelling index) was count using image analysis technique. RESULTS: No difference was observed of either apoptotic (10 vs. 11) or proliferation (35 vs. 25) index between early and advanced cancers. However, the apoptotic index was significantly higher in intestinal type advanced tumors. While both apoptotic and proliferation indices were significantly higher in tumors than in the adjacent mucosa, no difference was observed of either apoptotic (2 vs. 2) or proliferation (8 vs. 13) index between the tissues adjacent to early and advanced tumors. p53 protein expression was significantly higher in advanced cancers (7 vs. 5, p=0.001) and in the non-dysplastic tissue adjacent to advanced tumors (3.5 vs. 2, p=0.001). bcl-2 labelling index was significantly higher in the mucosa adjacent to advanced carcinomas (15 vs. 5, p=0.016) but this difference did not reach significance in the tumors (20 vs. 15, p=0.37). CONCLUSIONS: Our data indicate similar cell turnover during tumorigenesis of early and advanced cancer. p53 and bcl-2 protein accumulation is more intense in gastric mucosa adjacent to advanced tumors and p53 immunoreactivity peaks in advanced carcinomas.     

Helicobacter pylori Infection and Oncogene Expressions in Gastric Carcinoma and Its Precursor Lesions

Although it is fairly well accepted that Helicobacter pylori infection plays a significant role in causing gastric cancer, the exact mechanisms involved in its pathogenesis are unclear. We have examined the relationship between H. pylori infection and oncogene expression in different stages of disease progression from precursor lesions to gastric carcinoma. We used Diff-Quik stain to diagnose H. pylori infection and immunohistochemical stains against c-erbB-2, p53, ras, c-myc, and bcl-2 to determine expression of oncogenes. H. pylori infection was found in all cases of chronic gastritis, atrophic gastritis, intestinal metaplasia, and early gastric carcinoma, and in 16 of 30 (53%) cases of advanced gastric carcinoma. Overexpression of c-erbB-2 was found in 2 (7%) cases of advanced gastric carcinoma, which were H. pylori negative. Suppressor gene, p53, was overexpressed in 3 (30%) cases of intestinal metaplasia, 2 (33%) cases of early gastric carcinoma, and 18 (60%) cases of advanced gastric carcinoma. Of these 18 p53-positive advanced gastric cancer cases, 11 (61%) were H. pylori positive. Expression of ras p21 was found in 4 (40%) cases of H. pylori-negative normal mucosa, 10 (100%) cases of chronic gastritis, 1 (10%) case of atrophic mucosa, 6 (60%) cases of intestinal metaplasia, 2 (33%) cases of nonneoplastic mucosa adjacent to early gastric carcinoma, and 7 (23%) nonneoplastic mucosa adjacent to advanced gastric carcinoma, all of which showed H. pylori. No evidence of expression of either c-myc or bcl-2 was detected in any of the above-mentioned samples. The data suggest that H. pylori infection may increase expression of ras p21 proteins and induce p53 suppressor gene mutation early in the process of gastric carcinogenesis.     

胃粘膜癌变过程中幽门螺杆菌感染与p53,c-erbB-2基因表达的研究

目的探讨胃粘膜癌变过程中幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,Ｈｐ）感染与ｐ５３,ｃｅｒｂＢ２基因表达的关系．方法浅表性胃炎１６例,肠上皮化生２２例,异型增生１４例,早期胃癌１８例及进展期胃癌４０例作为研究对象．用ＷａｒｔｈｉｎＳｔａｒｙ银染色法检测Ｈｐ,用免疫组化Ｓｐ法检测ｐ５３和ｃｅｒｂＢ２的基因表达产物．结果Ｈｐ,ｐ５３,ｃｅｒｂＢ２在浅表性胃炎的检出率各为５００％,００％,００％;在肠上皮化生的检出率各为５９１％,２２７％,１３６％;在异型增生的检出率各为８５７％,６４３％,２８６％;在早期胃癌的检出率各为１６７％,３３３％,１１１％;在进展期胃癌的检出率各为５０％,５２５％,５５０％;在癌旁粘膜的Ｈｐ检出率为８６７％;在癌前病变中,Ｈｐ阳性组的ｐ５３,ｃｅｒｂＢ２表达率均高于Ｈｐ阴性组．结论Ｈｐ感染参与了胃癌前病变的发生与发展;Ｈｐ感染可引起野生型ｐ５３基因失活和ｃｅｒｂＢ２基因激活,从而导致胃粘膜的癌变．     

Nerve invasion as an independent predictor of poor prognosis in gastric cancer after curative resection

The study aims to reveal the clinical significance of perineural invasion (PNI) for gastric cancer prognosis and determine the risk factors of PNI in gastric cancer. This study retrospectively analyzed 350 patients who were diagnosed with GC and underwent curative surgical resection. Variables used to analyze survival included gender, age, degree of differentiation, T classification, lymph node metastasis, lymphovascular invasion, nerve invasion, mucinous adenocarcinoma component, and signet ring cell carcinoma component. The tumors of all patients were surgically resected. All resected specimens were stained with hematoxylin-eosin and immunohistochemical. The data for the patient’s lymphovascular invasion and PNI came from the collected pathological reports. The results of the survival analysis showed that T staging (P < .001), lymph node metastasis (P < .001), lymphovascular invasion (P = .013), PNI (P = .001), and signet ring cell carcinoma components (P = .046) affect the survival time and have a statistically significant difference. Multivariate analysis indicated that the positivity of PNI was an independent prognostic factor (P = .014). T staging (P = .006) and lymph node metastasis (P = .013) were independent prognostic parameters too. Using the Spearman correlation analysis, the following clinicopathological indicators were associated with PNI positivity, such as tumor differentiation, T staging, lymph node metastasis, vascular invasion, and signet ring cell carcinoma components (P < .05). PNI is an independent marker of poor prognosis in patients with gastric cancer.     

Gallbladder carcinoma: the role of p53 protein overexpression and Ki-67 antigen expression as prognostic markers

BackgroundThe overexpression of p53 protein and the expression of Ki-67 antigen may affect the survival of patients with gallbladder carcinoma. This association has been tested in a series of 41 patients with relatively early carcinoma of the gallbladder.MethodsForty-one surgical specimens from patients with a postoperative histological diagnosis of gallbladder carcinoma were studied. All patients were operated by simple cholecystectomy only because the tumours were not advanced and/or their general condition was poor. Patients submitted to radical operations were excluded. p53 expression was calculated from nuclear staining according to the intensity and extent of positive cells, as graded on a scale from 1 to 3; a combined score of >3 was considered as overexpression. Ki-67 expression was calculated by the MIB-I index: the percentage of positively stained tumour cell nuclei out of the total tumour cells counted (n = 1000); >20% of stained cells was considered positive.ResultsTwenty-nine gallbladder carcinomas (71%) overexpressed p53 protein in the cell nuclei. No significant differences were found in relation to cell differentiation on the level of tumour infiltration through the gallbladder wall. Five-year survival of patients with gallbladder carcinoma overexpressing p53 was 17.2%, while survival of patients without p53 overexpression was 30% (not significant). Twenty-four cases (58.5%) were considered positive for the MIB-I index. There were no differences between the grade of cell differentiation and wall infiltration. Five-year survival of the patients with a MIB-I positive index was 9.2% as opposed to 27.7% for those with a negative index (not significant).Conclusionsp53 protein nuclear overexpression and Ki-67 protein expression in gallbladder carcinoma were not related to histological differentiation, level of gallbladder wall invasion or patient survival.     

Expression of mutant p53 protein and CD44 variant proteins in colorectal tumorigenesis.

Colorectal tumorigenesis evolves through a series of molecular genetic changes, providing putative markers for tumour progression. This study investigated the relation between expression of the tumour suppressor gene p53 and splice variants v5 and v6 of the cell adhesion molecule CD44 by immunohistochemistry on tissue samples of early adenomas (n = 12), late adneomas (n = 12), Dukes's A and B carcinomas (n = 21), and Dukes's C and D carcinomas (n = 22) and compared these results with expression of these proteins in normal colonic mucosa (n = 17). A statistically significant trend of increasing expression was seen for both p53 (p < 0.005) and CD44 variant exon v6 (p < 0.0005) in subsequent stages of this tumour progression model. High expression of CD44 v5 was seen in most colorectal neoplasms (83%-96%), independent of stage. A statistically significant correlation was present between p53 expression and expression of variant v6 of CD44 (p < 0.01). Both p53 expression and CD44 v6 expression in adenomas increased with the degree of dysplasia (p < 0.05). The results of this study show that mutant p53 protein and variant v6 of the CD44 glycoprotein are markers of tumour progression in colorectal cancer.     

p16基因表达与胃癌组织类型的关系

目的：探讨ｐ１６基因的表达与人胃癌组织类型的关系。方法：选取２４例病理确诊的胃癌组织及相应正常胃粘膜组织，用蛋白质免疫印迹（Ｗｅｓｔｅｒｎ ｂｌｏｔ）技术检测ｐ１６基因在两种组织中的表达。结果：２４例胃癌组织中，６例无ｐ１６基因表达的癌组织为低分化腺癌或印戒细胞癌；２例ｐ１６基因表达可疑；分化较高的５例ｐ１６基因表达增多；其们１１例ｐ１６基因的表达同相应正常组织无区别。结论：ｐ１６基因在胃癌组织中     

Expression, deletion [was deleton] and mutation of p16 gene in human gastric cancer

AIM: To investigate the relationship between the expression of p16 gene and the gastric carcinogenesis, depth of invasion and lymph node metastases, and to evaluate the deletion and mutation of exon 2 in p16 gene in gastric carcinoma. METHODS: The expression of p16 protein was examined by streptavidin-peroxidase conjugated method (S-P);the deletion and mutation of p16 gene were respectively examined by polymerase chain reaction (PCR) and polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) in gastric carcinoma. RESULTS: Expression of p16 protein was detected in 96.25% (77/80) of the normal gastric mucosa, in 92.00% (45/50) of the dysplastic gastric mucosa and in 47.54% (58/122) of the gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma was significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P < 0.05). The positive rate of p16 protein expression in mucoid carcinoma 10.00% (1/10) was significantly lower than that in poorly differentiated carcinoma 51.22% (21/41), undifferentiated carcinoma 57.69% (15/26) and signet ring cell carcinoma 62.50% (10/16) (P < 0.05). The positive rate of p16 protein in 30 cases paired primary and lymph node metastatic gastric carcinoma: There was 46.67% (14/30) in primary gastric carcinoma, 16.67% (5/30) in lymph node metastatic gastric carcinoma. The positive rate of lymph node metastatic carcinoma was significantly lower than that of primary carcinoma (P < 0.05). There was of p16 gene mutation in exon 2, but 5 cases displayed deletion of p16 gene in exon 2 in the 25 primary gastric carcinomas. CONCLUSIONS: The expression loss of p16 protein related to the gastric carcinogenesis, gastric carcinoma histopathological subtypes and lymph metastasis. The mutation of p16 gene in exon 2 may not be involved in gastric carcinogenesis. But the deletion of p16 gene in exon 2 may be involved in gastric carcinogenesis.     

Goseki histological grading of gastric cancer is an important predictor of outcome.

TNM (tumour, node, metastases) staging has thus far been the most important guide to prognosis in patients with gastric cancer. Histological grading, in contrast, has not provided any additional information. Recently a novel grading system based on tubular differentiation and mucus production has been proposed, which was correlated with patterns of tumour spread found at necropsy. This study set out to assess its value as a determinant of survival after gastric resection. In a consecutive series of 211 patients who had potentially curative resection for gastric cancer, five histological grading systems were assessed: the Lauren type, the WHO type, degree of differentiation, the type of tumour border, and the lymphocytic response to the tumour and compared with the Goseki grading (I-IV). When T and N stage were taken into account, using Cox's proportional hazards model, only the Goseki grading added further to the ability to predict survival. The proportional hazards ratios were: node negative v node positive 6.5 T1 v T3 2.45; Goseki I v Goseki IV 3.1. Five year survival of patients with mucus rich (Goseki II and IV) T3 tumours was significantly worse than that of patients with mucus poor (Goseki I and III) T3 tumours (18% v 53%, p < 0.003). Goseki grading identifies subgroups of patients with a poorer prognosis than is predicted by TNM staging alone. It could prove useful in the selection of patients for adjuvant therapy after potentially curative resection for gastric cancer.     

Expression, deleton and mutation of p16 gene in human gastric cancer

AIM To investigate the relationship between the expression of p16 gene and the gastric carcinogenesis,depth of invasion and lymph node metastases, and to evaluate the deletion and mutation of exon 2 in p16 gene in gastric carcinoma. METHODS The expression of P16 protein was examined by streptavidin-peroxidase conjugated method (S-P); the deletion and mutation of p16 gene were respectively examined by polymerase chain reaction (PCR) and polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) in gastric carcinoma. RESULTS Expression of P16 protein was detected in 96.25% (77/80) of the normal gastric mucosa, in 92.00% (45/50) of the dysplastic gastric mucosa and in 47.54% (58/122) of the gastric carcinoma. The positive rate of P16 protein expression in gastric carcinoma was significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P＜0.05). The positive rate of P16 protein expression in mucoid carcinoma 10.00% (1/ 10) was significantly lower than that in poorly differentiated carcinoma 51.22% ( 21/ 41 ),undifferentiated carcinoma 57.69% (15/26) and signet ring cell carcinoma 62.50% (10/ 16) (P＜0.05). The positive rate of p16 protein in 30 cases paired primary and lymph node metastatic gastric carcinoma: There was 46.67% (14/30) in primary gastric carcinoma, 16.67% (5/30) in lymph node metastatic gastric carcinoma. The positive rate of lymph node metastatic carcinoma was significantly lower than that of primary carcinoma (P＜0.05). There was of p16 gene mutation in exon 2, but 5 cases displayed deletion of p16 gene in exon 2 in the 25 primary gastric carcinomas. CONCLUSIONS The expression loss of P16 protein related to the gastric carcinogenesis, gastric carcinoma histopathological subtypes and lymph metastasis. The mutation of p16 gene in exon 2 may not be involved in gastric carcinogenesis. But the deletion of p16 gene in exon 2 may be involved in gastric carcinogenesis.     

人结肠癌中凋亡抑制基因Survivin的表达

背景:细胞增殖和凋亡失衡将导致肿瘤的发生,并直接影响肿瘤的生物学行为。survivin是一种新的凋亡抑制基因,在大多数肿瘤中显著高表达。目的:探讨survivin基因在人结肠癌发生、发展中的作用,及其与p53基因的表达和结肠癌生物学行为的关系。方法:采用逆转录聚合酶链反应(RT鄄PCR)检测33例结肠癌组织及其相应癌旁组织和正常结肠黏膜中survivinmRNA和p53mRNA的表达,分析survivinmRNA的表达与p53mRNA的表达和结肠癌生物学行为的相关性。结果:69.7%的结肠癌组织中有survivinmRNA表达,表达率显著高于癌旁组织和正常结肠黏膜(42.4%和21.2%,P<0.01);survivin表达阴性癌组织的相应癌旁组织和正常结肠黏膜无一例有survivinmRNA表达。结肠癌组织中survivinmRNA的表达值显著高于癌旁组织和正常结肠黏膜(P<0.01)。33例结肠癌组织中仅2例p53mRNA表达缺失,癌旁组织和正常结肠黏膜中均有p53mRNA表达。结肠癌组织中p53mRNA的表达值与癌旁组织和正常结肠黏膜无显著差异;survivin表达阳性癌组织中p53mRNA的阳性表达率和表达值与survivin表达阴性组无显著差异。survivinmRNA和p53mRNA的表达与结肠癌的生物学行为无显著相关性。结论:survivin基因在人结肠癌组织中表达上调,提示其可能通过抑制结肠癌细胞凋亡,在结肠癌的发生、     

Endoscopic features of early-stage signet-ring-cell carcinoma of the stomach

AIM: To identify the features of early signet ring cell gastric carcinoma using magnification endoscopy with narrow band imaging (NBI).METHODS: A retrospective review was conducted of 12 cases of early signet ring cell gastric carcinoma who underwent treatment in a single institution between January 2009 and April 2013. All patients had magnification endoscopy with NBI and indigo carmine contrast to closely examine the mucosal architecture, including the microvasculature and arrangement of gastric pits. Histologic examination of the final endoscopic submucosal dissection or gastrectomy specimen was performed and compared with the endoscopic findings to identify patterns specific to signet ring cell carcinoma.RESULTS: Twelve patients with early signet ring cell gastric carcinoma were identified; 75% were male, and average age was 61 years. Most of the lesions were stage T1a (83%), while the remainder were T1b (17%). The mean lesion size was 1.4 cm². On standard endoscopy, all 12 patients had a pale, flat lesion without any evidence of mucosal abnormality such as ulceration, elevation, or depression. On magnification endoscopy with NBI, all of the patients had irregularities in the glands and microvasculature consistent with early gastric cancer. In addition, all 12 patients exhibited the “stretch sign”, an elongation or expansion of the architectural structure. Histologic examination of the resected specimens demonstrated an expanded and edematous mucosal layer infiltrated with tumor cells.CONCLUSION: The “stretch sign” appears to be specific for signet ring cell carcinoma and may aid in the early diagnosis and treatment of this aggressive pathology.     

Immunohistochemical expression of cell-cycle proteins in gastric precancerous lesions

Background: The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27^kip1 play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions. Methods: A total of 1 45 endoscopic gastric biopsy specimens of AG, IM, and gastric dysplasia were studied. These molecular markers were localized by immunohistochemistry. Results: P53 was expressed in 15% of cases with gastric dysplasia and not in the pre‐dysplastic stages of the gastric mucosa. All cases were concerning high‐grade dysplasia. Cyclin D1 protein was almost undetectable in the precancerous lesions of gastric cancer. Cyclin D3 protein overexpression was seen in 10% of biopsies with IM, and 50% of biopsies with gastric dysplasia. High expression of p27^kip1 protein was demonstrated in all cases of chronic gastritis. As atrophy, IM, and dysplasia develop, expression of p27^kip1 protein is suppressed. In total, 15% of dysplastic cases showed no expression of p27^kip1 protein. Conclusions: (i) P53 mutation must be a late event during the development of gastric cancer. (ii) Cyclin D1 protein overexpression may not play a role in the progression from normal to neoplastic gastric mucosa, while overexpression of cyclin D3 is an earlier event during gastric carcinogenesis, and its role must be further evaluated. (iii) Reduced expression of p27^kip1 is a rather early event in gastric tumorigenesis, before dysplastic changes occur.     

Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis via retinoblastoma pathway

AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb)tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to explain the observed striking epidemiological differences.METHODS: Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour.RESULTS: In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional)decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections)to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections.CONCLUSION: Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis.Tt may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.     

Differences in proximal （cardia） versus distal （antral） gastric carcinogenesis via retinoblastoma pathway

AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb) tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to explain the observed striking epidemiological differences. METHODS: Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour. RESULTS: In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional) decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections) to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections. CONCLUSION: Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis. It may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.     

胃癌及癌前病变中p53蛋白的检测及意义

探讨p53蛋白表达与胃癌及癌病变的相互关系,方法：用免疫组化染色示检测33例肠化,26例异型增生和26例胃癌组织中p53蛋白的表达。结果：p53蛋白在胃癌组织中表达率最高（61．5％）,在异型增生和肠化组织中的表达率分别为34．6％和12．1％,组间有显著差异,各期胃癌组织中p53蛋白的表达无显著差异,结论：p53蛋白在胃癌前病变中已有阳性表达,在肠化、异型增生及胃癌组织中,其表达率依次增高,p53蛋白积累主要发生在癌前病变晚期及胃癌早期,其表达与胃癌发生密切相关。