Overexpression of cyclins D1 and E is frequent in bronchial preneoplasia and precedes squamous cell carcinoma development.

Increased protein expression of the G1 cyclins D1 and E is reported in invasive non-small cell lung carcinoma. However, during transformation of the bronchial epithelium, overexpression of these species occurs, and their relationship to aberrant expression of p53 and retinoblastoma (Rb) has not been described previously. To determine the expression of these cell cycle regulators during the development of invasive squamous cell carcinoma (SCC) of the lung, the immunohistochemical expression patterns in normal bronchial epithelium (n = 36), squamous metaplasia (SM; n = 28), and epithelial atypia (n = 34) were compared with that in low-grade dysplasia (LGD; n = 17), high-grade bronchial dysplasia (HGD; n = 30), and SCC (n = 36). Monoclonal anti-p53 Pab1801, polyclonal anti-cyclin D1 DCS6, monoclonal anti-cyclin E HE12, and monoclonal anti-Rb OP-66 antibodies were used. Cyclin D1 was not expressed in normal bronchial epithelium but was detected in 7% of SMs, 15% of atypias; 18% of LGDs, 47% of HGDs, and 42% of SCCs. Cyclin E was not detected in normal epithelium (n = 24), SM (n = 16), or LGD (n = 12), but it was found in 9% of atypias (2 of 22), 33% of HGDs (7 of 21), and 54% of SCCs (13 of 24). p53 was not expressed in normal epithelium, SM, and LGD, but it was overexpressed in 6% of atypias, 53% of HGDs, and 61% of SCCs. Abnormal Rb expression was found only in 2 of 36 cases of SCC. A total of 91% of HGDs and 92% of SCCs exhibited overexpression of at least one of the p53, cyclin D1, or cyclin E species. However, no link was observed between overexpression of p53 and the overexpressed G1 cyclins in preneoplastic lesions. Overexpression of cyclin D1, cyclin E, and p53 occurs frequently and independently in pulmonary SCC and is detected in lesions before the development of invasive carcinoma. In contrast, altered Rb expression is a late and infrequent event in squamous cell carcinogenesis.     

Significance of COX-2 expression in human esophageal squamous cell carcinoma

Cyclooxygenase-2 (COX-2) is well established to play an important role in the tumorigenesis of a variety of human cancers; however, the function of COX-2 in the development of esophageal squamous cell carcinoma (ESCC) remains less clear. Here, we determined, first, the pattern of COX-2 expression in normal esophageal mucosa, dysplasia, carcinoma in situ (CIS) and invasive SCC. Immunohistochemical analysis showed that, while COX-2 was weakly expressed, if at all, in normal squamous epithelium, strong COX-2 expression was detected as early as the stage of dysplasia and frequently in 20 of 26 (77%) CIS and 86 of 111 (77%) invasive SCC. Upregulation of COX-2 in ESCC was found to be significantly associated with tumor progression (R = 0.493, P < 0.01). Further, treatment of human ESCC cell lines (KYSE450 and KYSE510) with NS-398, a COX-2 specific chemical inhibitor, suppressed the production of prostaglandin E2 (PGE2) and induced cell growth inhibition, cell cycle arrest at the G1-S checkpoint, and the expression of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1. Finally, knockdown expression of COX-2 in KYSE450 cells by a specific COX-2 siRNA dramatically inhibited PGE2 production, cell growth and, more importantly, colony formation and tumorigenesis in nude mice. Together, this study suggested that COX-2 may be involved in an early stage of squamous cell carcinogenesis of the esophagus and has a non-redundant role in the regulation of cellular proliferation and tumorigenesis of esophageal epithelial cells.     

Immunohistochemical analysis of cyclooxygenase-2 expression in premalignant and malignant esophageal glandular and squamous lesions in Cixian,China

Increased cyclooxygenase-2 (COX-2) expression has been observed in both squamous cell carcinoma (SCC) and adenocarcinoma (AC) in Western countries, and COX-2 inhibitors have been considered as potential chemopreventive agents for esophageal cancers. Since chemoprevention often targets the premalignant lesions in high-risk population, it is worthwhile to study COX-2 expression in a spectrum of premalignant and malignant lesions obtained from the high-risk populations. In this study, biopsy samples were taken from 240 subjects identified by screening of the high-risk population in Cixian, China, including 27 normal, 29 with squamous hyperplasia, 84 with dysplasia (31 low grade and 53 high grade), 30 with carcinoma in situ, and 70 with invasive carcinoma (60 SCC and 10 AC). For comparison, tissue samples were also collected from He Lon Jiang Province, a low-risk population in China, including 10 patients with invasive SCC, 20 patients with AC, and 17 patients with Barrett's esophagus. The COX-2 protein expression was examined by immunohistochemistry. Using 10% staining as a threshold, 9 of 10 (90%) invasive SCC from low-risk population were COX-2 positive. However, no positive COX-2 staining was seen on normal, hyperplastic, dysplastic, and in situ squamous lesions from the high-risk population, and only 4 of 60 (6%) invasive SCC exhibited positive COX-2 staining. For glandular lesions, 6 of 10 (60%) AC from high-risk area and 15 of 20 (75%) from low-risk area showed positive COX-2 staining, and 12 of 17 (70%) premalignant Barrett's esophagus were also positive. Our findings show that COX-2 expression various in squamous lesions from high- and low-risk areas, but not in glandular lesions. Additional studies are needed to fully explore the mechanisms that are associated with the different COX-2 immunohistochemical staining patterns in esophageal squamous lesions from low- and high-risk populations.     

Expression of cyclin E in dysplasia, carcinoma, and nonmalignant lesions of Barrett esophagus

BACKGROUND: Barrett esophagus (BE) is a condition in which the normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. BE is a premalignant lesion because it is the initiating factor in a metaplasia-dysplasia-carcinoma sequence. METHODS: Expression of the proliferation-associated molecule cyclin E was immunohistochemically determined in metaplastic specialized epithelium (SE; n = 24), low grade dysplasia (LGD; n = 21), high grade dysplasia (HGD; n = 17), and invasive adenocarcinoma (CA; n = 35) from 36 esophagectomy specimens. In addition, endoscopically obtained samples of SE with minimal inflammatory changes (n = 11) and SE adjacent to erosions or ulcerations were tested for cyclin E expression. RESULTS: In the surgical specimens, expression of cyclin E was found in 0 of 24 SE (0%), 2 of 21 LGD (9.5%), 3 of 17 HGD (17.6%), and 5 of 35 CA (14. 3%). In the biopsy specimens, expression of cyclin E was found in all samples adjacent to erosions or ulcerations, whereas SE with minimal inflammatory changes was invariably negative for cyclin E. CONCLUSIONS: Accumulation of cyclin E can be found by means of immunohistochemistry in premalignant and malignant lesions in BE as well as in regenerative metaplastic epithelium. The determination of cyclin E expression is therefore not useful in the identification of BE patients with an increased risk for the development of carcinoma.     

Expression of cyclin B1 in the metaplasia-dysplasia-carcinoma sequence of Barrett esophagus

BACKGROUND: It is known that proliferation is deregulated progressively during carcinogenesis in Barrett esophagus (BE). Cyclin B1 is a key protein for the regulation of G2-M-phase transition during the cell cycle and is essential for initiation of mitosis. METHODS: Using immunohistochemistry, samples of Barrett metaplastic specialized epithelium (SE; n = 36 samples), low-grade dysplasia (LGD; n = 25 samples), high-grade dysplasia (HGD; n = 25 samples), and invasive adenocarcinoma (CA; n = 46 samples) derived from 50 esophagectomy specimens were investigated for the expression of cyclin B1. The number of cyclin B1 positive cells was determined semiquantitatively. In addition, in SE, LGD, and HGD samples, the pattern of cyclin B1 expression was assessed by determination of the presence of positive cells in four mucosal compartments: the deep glandular zone, the lower crypt zone, the upper crypt zone, and the luminal surface. RESULTS: Cyclin B1 expression was found in all lesions under investigation. Regarding the percentage of positive cells, a marked increase of cyclin B1 positive cells was observed in SE samples compared with LGD samples and in HGD samples compared with CA samples (chi-square test; P < 0.0001), nevertheless showing a broad overlap between the different lesions. Concerning staining patterns, in the majority of SE samples (72.2%), cyclin B1 positive cells were restricted to the glandular zone and the lower crypt zone. In contrast, an expansion of cyclin B1 positive cells to superficially located zones of the mucosa (the upper crypt zone and/or the luminal surface) was observed in the majority of LGD samples (96.0%) and HGD samples (100%; P < 0.0001). CONCLUSIONS: Overexpression of cyclin B1 is a frequent and early finding in the metaplasia-dysplasia-carcinoma sequence in BE. It may contribute to the loss of growth control and, subsequently, to the development of tumors in this location.     

p53 Protein accumulation, cancer multiplicity, and aldehyde dehydrogenase-2 genotype in Japanese alcoholic men with early esophageal squamous cell carcinoma

Synchronous multiple intra-esophageal squamous cell carcinomas (SCCs) or oropharyngolaryngeal SCCs are common in alcoholics with esophageal SCC, and more frequently found in those with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2). p53 alterations have been suspected as key molecular events in such multifocal esophageal carcinogenesis. We studied 95 Japanese alcoholic men with Tis and mucosal invasive esophageal SCC and found very high levels of p53 protein accumulation occurring in early esophageal SCC. Synchronous cancer multiplicity in the upper aerodigestive tract was found in 40 patients. p53 expression was not correlated with either cancer multiplicity or ALDH2 genotype. The risk for cancer multiplicity was associated with inactive heterozygous ALDH2 alone (OR=4.22) among the risk factors investigated, which also included smoking, less-active alcohol dehydrogenase-1B, and macrocytosis, enhancing the validity of the link between acetaldehyde exposure and cancer multiplicity.     

Telomere shortening is correlated with the DNA damage response and telomeric protein down-regulation in colorectal preneoplastic lesions

BackgroundA relation between telomere attrition in early carcinogenesis and activation of DNA damage response (DDR) has been proposed. We explored telomere length and its link with DDR in colorectal multistep carcinogenesis.Patients and methodsWe studied normal mucosa, low-grade dysplasia (LGD) and high-grade dysplasia (HGD) and invasive carcinoma (IC) in matched human colon specimens by evaluating p-ataxia telangiectasia mutated (ATM), p-checkpoint kinase 2 (Chk2), c-H2AX, TRF1 and TRF2 expressions by immunohistochemistry. FISH was used to assess telomere length.ResultsTelomeres shortened significantly from normal (N) to LGD and HGD (P < 0.0001; P = 0.012), then increased in length in IC (P = 0.006). TRF1 and TRF2 expressions were diminished from N to LGD and HGD (P = 0.004, P < 0.0001, ns) and were reexpressed at the invasive stage (P = 0.053 and P = 0.046). Phosphorylated ATM, Chk2 and H2AX appeared already in LGD (respectively, P = 0.001, P = 0.002 and P = 0.02). Their expression decreased from HGD to IC (respectively, P = 0.03, P = 0.02 and P = 0.37). These activating phosphorylations were inversely correlated with telomere length and TRF1/2 expression.ConclusionIn a model of colon multistep carcinogenesis, our data indicate that telomeric length and protein expression levels are inversely correlated with the activation of the DDR pathway.     

Topological analysis of p21WAF1/CIP1 expression in esophageal squamous dysplasia.

In the normal stratified squamous epithelium of the esophagus, only the third to the fifth layers of cells express the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21). Using immunohistochemical staining, we examined the topological distribution of cells expressing p21, p53, Ki67, and cytokeratin 10 (CK10), a differentiation marker of esophageal squamous cell carcinoma (SCC), in 25 superficial SCCs and 72 dysplastic lesions of the esophagus. Image analysis of p21, p53, and Ki67 expression was also performed in 48 dysplastic lesions. In superficial SCCs, although Ki67- and p53-expressing cells were mainly distributed in the deep layers of tumors despite tumor differentiation, the distribution of p21 correlated with tumor differentiation. In dysplastic lesions, p53- and Ki67-coexpressing cells tended to locate in the same layers and expand in the lower layers of epithelium with the progression of dysplasia. p21-expressing cells shifted to the upper layers of the epithelium with the progression of dysplasia. However, this change was heterogeneous; in some lesions, p21-expressing cells were confined to the superficial layers of atypical cells (confined type), whereas in others, p21-overexpressing cells were scattered among atypical cells (scattered type). CK10 expression was observed in 25% of dysplastic lesions, and the frequency of CK10 expression was significantly higher in the scattered than in the confined type. Our results suggest that esophageal squamous dysplasia represents the earliest pathological process in esophageal squamous carcinogenesis. Our results also suggest that differentiation of esophageal SCC is determined at the stage of dysplasia, and that p21 plays a critical role in the differentiation process.     

Topographical analysis of p53 expression and DNA ploidy in early bronchial squamous cell carcinoma and preneoplastic lesions.

The significance of p53 mutations and DNA aneuploidy in carcinoma cells has been investigated on the basis of a multi-step development theory of carcinogenesis. It has, however, not been determined whether these alterations can be used as diagnostic markers for the early detection of bronchial squamous cell carcinoma (BSqCC). To address this problem, we topographically investigated p53 alterations and DNA aneuploidy in 24 X-ray-negative, early BSqCC patients with various preneoplastic lesions and in 25 non-carcinoma patients with preneoplastic lesions. Bronchial lesions (n=88) were morphologically classified as hyperplasia (HP, n=5), squamous metaplasia (SM, n=23), low-grade dysplasia (LGD, n=14), high-grade dysplasia (HGD, n=11), intraepithelial carcinoma including 'carcinoma in situ' (CIS) (IEC, n=15), and microinvasive carcinoma (MIC, n=20). Immunohistochemistry for the p53 protein and image cytometry for DNA ploidy detection were performed in serial sections of each lesion. Overexpression of p53 protein was detected in 36, 73, and 65% of the HGD, IEC, and MIC lesions, respectively. Aneuploid DNA profiles were found only in carcinoma lesions, 33% in IEC and 85% in MIC. The topographical analysis revealed two types of early BSqCCs, one with adjacent preneoplastic lesions (sequential type, n=8) and another without such lesions (de novo type, n=16). The p53 protein was frequently overexpressed in both types (sequential type, 79%; de novo type, 62%). In the sequential type, however, the p53 protein was overexpressed in HGD lesions that were directly adjacent to p53-overexpressing carcinoma lesions without exception. The present topographical study suggests that p53 mutations play an important role in the carcinogenesis of BSqCC and that p53-overexpressing HGD lesions in sequential types should be regarded as 'truly' preneoplastic lesions that actually develop into carcinomas. In addition, our study demonstrated that DNA aneuploidy might occur at times after p53 alteration with increasing frequency, as invasive growth begins. Such combination analysis of p53 immunohistochemistry and nuclear DNA ploidy in routine histology may contribute to estimates of malignant potential in preneoplastic and intraepithelial squamous lesions and provide additional information for early detection of BSqCC.     

Global analysis of altered gene expressions during the process of esophageal squamous cell carcinogenesis in the rat: a study combined with a laser microdissection and a cDNA microarray

The genetic alterations that occur during esophageal tumorigenesis have yet to be determined. We previously established a Wister rat carcinogenesis model of esophageal squamous cell carcinoma. To understand more about the molecular mechanisms during carcinogenesis, we produced esophageal neoplastic lesions by administering N-amyl-N-methylnitrosamine and 12-O-tetradecanoylphorbol-13-acetate to rats. We used laser microdissection to specifically isolate the cells from the normal epithelium, papilloma, dysplasia, and invasive carcinoma. Using a cDNA microarray representing 14,815 clones, we then analyzed the gene expression profiles for each esophageal lesion. The number of differentially expressed genes compared with the normal control dramatically increased in a step-by-step fashion from normal epithelium (1,151 +/- 119 genes) to papilloma (1,899 +/- 543 genes), dysplasia (1,991 +/- 193 genes), and invasive carcinoma (2,756 +/- 87 genes). A hierarchical clustering analysis showed that the three stages of normal epithelium, dysplasia (papilloma), and invasive carcinoma could be clearly classified, whereas the gene expression patterns of papilloma and dysplasia were indistinguishable. Using the Fisher criterion, we also identified 50 genes whose expression level had either significantly increased or decreased in a step-by-step manner from the normal epithelium to dysplasia and then finally to invasive carcinoma. Many of these genes were not previously known to be associated with esophageal carcinogenesis. The present findings in our rat model thus seem to provide us with a better understanding of the molecular alterations that occur during esophageal carcinogenesis and hopefully will also help lead to the development of novel diagnostic and therapeutic targets.     

Significance of cyclin B1 expression as an independent prognostic indicator of patients with squamous cell carcinoma of the esophagus.

PURPOSE: Cyclin B1 plays an important role as a mitotic cyclin in the G(2)-M phase transition during the cell cycle. The aim of the present study was to elucidate the biological significance of cyclin B1 expression in squamous cell carcinoma (SCC) of the esophagus. EXPERIMENTAL DESIGN: We analyzed immunohistochemically the expression of cyclin B1 in the tumor specimens from 120 patients with SCC of the esophagus that had been treated with surgical treatment without any preoperative therapies. RESULTS: The positivity rate of cyclin B1 expression was 56.7% (68 of 120). One-, 3-, and 5-year survival rates in esophageal SCCs with cyclin B1 expression were 82.8, 61.6, and 50.7%, respectively, and they were significantly lower than those in esophageal SCCs without cyclin B1 expression (97.8, 85.5, and 78.6%, respectively; P = 0.005). Cyclin B1 expression was found to be an independent prognostic indicator in esophageal SCCs in a multivariate analysis. When immunostaining for cyclin B1 was classified as a nuclear dominant pattern and cytoplasmic dominant pattern, 1-, 3-, and 5-year survival rates in esophageal SCCs with nuclear dominant expression of cyclin B1 were 66.7, 47.9, and 28.7%, respectively, and they were significantly lower than those in esophageal SCCs with cytoplasmic dominant expression (92.5, 70.0, and 66.3%, respectively; P = 0.005). A multivariate analysis demonstrated that the nuclear dominant cyclin B1 expression was an independent prognosticator in patients with esophageal SCCs expressing cyclin B1. CONCLUSIONS: Our results demonstrate that cyclin B1 expression, especially nuclear dominant expression, can be significant as a prognostic indicator in esophageal SCCs.     

Expression of cyclooxygenase-2 is associated with carcinogenesis of the lower part of thoracic esophageal squamous cell carcinoma and p53 expression.

Cyclooxygenase (COX) is a key enzyme in arachidonic acid metabolism. Two isoforms of this enzyme have been identified: constitutive COX-1 and inducible COX-2. Recently, expression of COX-2 has been found in several human carcinomas. COX-2 expression may contribute to the synthesis of prostanoids, which relate to carcinogenesis and tumor progression. We investigated the expression of COX-2 in 175 human esophageal squamous cell carcinoma tissues using immunohistochemistry and evaluated the relationship with clinicopathological findings. In addition, due to the known relevance of p53 to carcinogenesis, we evaluated the expression of COX-2 and p53. Interestingly, cancer tissues with high COX-2 expression were found significantly more often in the middle and lower esophagus than in the cervical and upper esophagus (p = 0.0014). No significant differences were observed in other clinicopathological data such as age, sex, histopathological grading, lymphatic invasion, venous invasion, TNM clinical classification and patient prognosis. p53 expression was associated with the expression of COX-2 (p = 0.0122). Our findings suggest that COX-2 may play a role in the development of squamous cell carcinoma in the lower part of the thoracic esophagus.     

食管鳞癌及癌前病变活检组织的微卫星改变

目的 探讨食管鳞状细胞癌（ESCC）早期病变与遗传学改变之间的关系，筛选和评价可能作为食管癌早期诊断预警指标的微卫星标志物。方法 选用曾被证实在浸润性食管鳞癌表现高频率杂合性缺失（LOH）的16个同位素标记微卫星标志物，应用激光捕获显微切割技术（LCM）分析37例食管镜活检组织不同程度病变存在的遗传学改变，包括15例不典型增生，22例ES-CC。结果 16个微卫星标志物LOH频率和微卫星不稳定性（MSI）发生率分别为：轻度不典型增生（LGD）为2%和22%，重度不典型增生（HGD）为15%和33%，ESCC为35%和64%，LGD与HGD比较有非常显著性差异（P=0.02,P=0.001,P=0.007)；HGD与ESCC比较无显著性差异。其中的10个标志物（D3S4545，D5S2501，D8S1106，D9S1118，D9S910，D13S1493，D13S894，D13S796，D15S655，D17S1303）分别在1例以上的癌前病变中出现等位缺失。结论 LDH和MSI的发生频率均随病变的组织学严重程度而增高，且等位缺失在食管癌前病变检出率较高，食管癌的发生和进展与基因不稳定性密切相关，这种分子改变能够通过食管镜活检组织检测。微卫星标志物可能成为食管癌早期诊断的有用标志物。     

Endoscopic therapy of esophageal premalignancy and early malignancy

Esophageal adenocarcinoma (EAC) is an often deadly cancer with a rising incidence in Western countries. Chronic gastroesophageal reflux disease is associated with the metaplastic transformation of normal squamous epithelium to premalignant specialized intestinal metaplasia within the esophagus (Barrett's esophagus). Barrett's esophagus may progress to low-grade dysplasia (LGD), high-grade dysplasia (HGD), or even EAC. Although nondysplastic Barrett's esophagus progresses to EAC at a rate of 0.5% per year, rates of progression for true LGD and HGD are significantly higher. Treatment is mandatory for HGD and may be appropriate in select patients with nondysplastic Barrett's esophagus and many with LGD. Thus, accurate pathologic assessment is necessary before considering endoscopic therapy. Previously, only esophagectomy was offered to patients with HGD or EAC. However, esophagectomy has significant morbidity and mortality, and therefore endoscopic therapies have been advocated for early Barrett's neoplasia. These methods include endoscopic mucosal resection (EMR) and ablative techniques. Ablation techniques include argon plasma coagulation, multipolar electrocoagulation, laser therapy, photodynamic therapy, radiofrequency ablation, and cryotherapy. Of these, radiofrequency ablation has experienced the greatest adoption for the treatment of dysplastic Barrett's esophagus because of excellent published outcomes. The use of EMR to resect suspicious areas or raised lesions is mandatory to provide histology. In contrast, ablation techniques such as radiofrequency ablation have been shown to effectively eradicate large areas of dysplastic tissue with relative ease but do not allow for histologic assessment of the treated area. Combination EMR with radiofrequency ablation is thus advocated to resect visible lesions via EMR (providing histology) and ablate the remainder of the Barrett's esophagus. As always, the appropriate treatment is best determined after careful discussion with patients in a multidisciplinary environment. However, endoscopic therapy offers an attractive alternative to esophagectomy for early Barrett's neoplasia.     

Smoking-related increase of O(6)-methylguanine-DNA methyltransferase expression in squamous cell carcinoma of the esophagus

DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) has a defensive role against alkylating agents associated with increased incidence of malignant tumors. The aim of the current study was to elucidate the significance of immunohistochemical expression of MGMT in squamous cell carcinoma (SCC) of the esophagus, with a special reference to the correlation of smoking. Immunohistostaining of MGMT was performed in the specimens collected from 100 patients with SCC of the esophagus. The relationship between the personal history of smoking and MGMT expression was examined and the value of Brinkman index was compared between patients with and without MGMT expression. Fifty-five SCCs (55.0%) had a positive response to MGMT inununostaining. The proportion of patients who had tumors with MGMT expression among patients with smoking habits was 62.0% (49 out of 79), which was significantly higher than that among patients without smoking habits (28.6%, 6 out of 21; P=0.005). The mean value of Brinkman index in patients who had tumors with MGMT expression (1189+/-604) was significantly higher than that in patients who had tumors without MGMT expression (871+/-656; P=0.020). Our results suggested that MGMT expression in esophageal SCC might be correlated with smoking habits of the patients.     

Expression of GST-π gene in human esophageal carcinogenesis

Objective: To investigate the possible role of GST-π in esophageal carcinogenesis. Methods: GST-π expression at mRNA level was studied by in situ hybridization (ISH) and at protein level by immunohistochemistry (IHC). GST-π expression in normal epithelial cells (NC) of the esophagus, hyperplastic cells (HC), dysplastic cells (DC) from grade I to III, carcinoma in situ (CIS) and all the cells in squamous cell carcinomas (SCC) were examined in the same esophageal cancer specimens (n=48) which provided a model reflecting the process of esophageal carcinogenesis. Results: The positive rate of IHC staining was 87.5% for NC, 95.3% for HC, 55.9% for DC (grade I: 73.9%, grade II: 47.4%, grade III: 41.2%), 36.4% for CIS and 45.8% for SCC. The positive rate of GST-π mRNA expression was 81.2% for NC, 94.4% for HC, 61.9% for DC (grade I: 76.5%, grade II: 61.5%, grade III: 41.7%), 44.4% for CIS and 83.3% for grade I SCC, 30.0% for grade II SCC and 0% for grade III SCC. There was no statistically significant difference in GST-π expression at the mRNA and the protein level. Conclusion: There is a decreasing tendency of GST-π expression from dysplasia to CIS and SCC. The decrease in GST-π expression is an early event in esophageal carcinogenesis. This work was supported by a grant from the Key Project of Henan Province Science Foundation (No. 961001)