Changes in p53 and Waf1p21 expression and cell proliferation in esophageal carcinogenesis

AIM: To study the correlation between changes in p53 and Waf1p21 expression and cell proliferation, determined by proliferating cell nuclear antigen (PCNA), at different stages of human esophageal carcinogenesis.METHODS: Biopsied and resected esophageal tissues from a high risk population of esophageal cancer in northern China were used in this study. All specimens were fixed in 85% alcohol and processed for routine histology. The avidin biotin peroxidase complex (ABC) method was used to detect p53, Waf1p21 and PCNA.RESULTS: Strong nuclear staining of p53, Waf1p21 and PCNA was observed in normal esophageal epithelium and epithelia with different lesion severities. As the lesions progressed to dysplasia (DYS) and to esophageal squamous cell carcinoma (SCC), the Waf1p21 immunoreactivity percentage decreased. The number of Waf1p21-positive cells slightly increased from normal to basal cell hyperplasia (BCH), but did not further increase in DYS and SCC. The total number of Waf1p21-positive cells was lower than the number of p53-positive cells in normal and BCH esophageal epithelia and much lower in DYS and SCC. Waf1p21-positive cells were located in the third and fourth cell layers in half of the samples examined, which was 2-4 cell layers higher than the cells expressing PCNA and p53 in the same histological categories of normal, BCH and DYS.CONCLUSION: Low Waf1p21 levels at the DYS stage may be related to a functional loss of p53. Other mechanisms may also be responsible for the decreased Waf1p21 expression in DYS and SCC.     

Endoscopic screening and determination of p53 and proliferating cell nuclear antigen in esophageal multistage carcinogenesis: a comparative study between high- and low-risk populations in Henan, northern China

The objective of this study was to characterize the histologic changes from endoscopic screening for early esophageal cancer (EC) on subjects at high-incidence area (HIA) and low-incidence area (LIA) in Henan, China, and to further compare the changes in p53 and proliferating cell nuclear antigen (PCNA) in the multistage of human esophageal carcinogenesis from these two populations. The detection rate of basal cell hyperplasia (BCH) and dysplasia (DYS) was higher in the subjects from HIA than in those from LIA. Out of the 1568 symptom-free subjects examined at HIA, 10 (0.6%) cases with early squamous cell carcinoma (SCC) were identified. Immunoreactivity of p53 and PCNA was observed in cell nuclei of esophageal biopsies and surgically resected esophageal cancer specimens both in HIA and LIA. With the lesions progressed from normal epithelium to BCH to DYS to SCC, the positive-immunostaining cells expanded from basal layer to superficial layer, and the number of positive cells/mm2 for p53 and PCNA increased, and was significantly higher in HIA than in LIA among the similar morphological lesions (P < 0.01). The number of p53 positive cells/mm2 in SCC from HIA was almost fivefold higher than SCC from LIA (P < 0.01). The remarkable difference was also observed between HIA and LIA in DYS and BCH. The present results indicate that p53 protein accumulation is an important early biomarker for identifying high-risk subjects for EC.     

Alterations of p53 and PCNA in cancer and adjacent tissues from concurrent carcinomas of the esophagus and gastric cardia in the same patient in Linzhou,a high incidence area for esophageal cancer in northern China

AIM:To characterize the alteration and significance of p53 and PCNA in cancer and adjacent tissues of concurrent cancers from the esophagus and gastric cardia in the same patient.METHODS: P53 and PCNA protein accumulation in 25 patients with concurrent cancers from the esophagus and gastric cardia (CC, concurrent carcinomas of esophagealsquamous cell carcinoma and gastric cardia adenocarcinoma)were detected by immunohistochemical method (ABC).RESULTS: In CC patients, both esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA)tissues showed different positive immunostaining extent ofp53 and PCNA protein (P&gt;0.05). The positive immunostainingrates for p53 and PCNA were 60 % (15/25) and 92 % (23/25), respectively in SCC; and 40 % (10/25) and 88 % (22/25), respectively in GCA. “Diffuse“ immunostaining patternwas frequently observed in both p53 and PCNA. High coincidence rates for p53 and PCNA positive staining were observed in SCC and GCA from the same patients, andaccounted for 56 % and 96 %. In SCC patients, with thelesions progressed from normal esophageal epithelium (NOR)to basal cell hyperplasia (BCH) to dysplasia (DYS) tocarcinoma in situ (CIS) to SCC. the oositive rates for p53were 27 %, 50 %, 50 %, 29 % and 72 %, and 55 %, 70 %,75 %, 71% and 93 % for PCNA, respectively. In GCA, with the lesions progressed from normal gastric cardia epithelium to DYS to CIS to GCA, the positive rates of p53 expression were 44 %, 27 %, 22 % and 36 % respectively, the difference was not significant; the positive rates of PCNA protein expression were 67 %, 64 %, 67 % and 86 %, respectively.The χ^2 test, Fisher‘s Exact Test, Mantel-Haenszel χ^2 Test and Kappa Test were used for the statistics.CONCLUSION: The high coincident alterations for P53 and PCNA in SCC 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 SCC and GCA.Chen H, Wang LD, Guo M, Gao Alterations of p53 and PCNA inSG, Guo HQ, Fan ZM, Li JL.cancer and adjacent tissuesfrom concurrent carcinomas of the esophagus and gastric cardiain the same patient in Linzhou, a high incidence area foresophaqeal cancer in northern China. World J Gastroenterol     

Expressions of PCNA, p53, p21WAF-1 and cell proliferation in fetal esophageal epithelia: Comparative study with adult esophagea lesions from subjects at high-incidence area for esophageal cancer in Henan, North China

AIM: To characterize the expression of p53, p21WAF-1 and proliferation-cell-nuclear-antigen (PCNA) in fetal esophageal epithelia and to determine the role of these genes in proliferation of fetal and adult esophageal epithelial cells.METHODS: Immunohistochemical avdin-biotin peroxidase complex (ABC) method was applied to 31 cases of fetal esophageal specimens and 194 cases of adult esophageal specimens to detect the expression of p53, p21WAF-1 and PCNA in fetal and adult esophageal epithelia.RESULTS: Both the PCNA positive immunostaining cell number and PCNA positive immunostaining rate in fetal esophageal epithelia (506±239) were significantly higher than those in adults,including normal epithelia (200±113) and epithelia with basal cell hyperplasia (BCH) (286±150) (P＜0.05, ttest). However,the number of PCNA positive immunostaining cells in adult esophageal dysplasia (719±389) and squamous cell carcinoma (SCC) (1261±545) was apparently higher than that in fetal esophageal epithelia (506±239) (P＜0.05, ttest). The positive immunostaining rate of P53 was 10 % (3/3L) in fetal esophageal epithelia, which was significantly lower than that in adult normal esophageal epithelia (50 %), adult epithelia with basal cell hyperplasia (62 %), dysplasia (73 %) and squamous cell carcinoma (86 %) (P＜0.05, Fisher′s exact test). No p21WAF-1positive immunostaining cells were observed in fetal esophageal epithelia. However, p21WAF-1 positive immunostaining cells were observed in adult esophagus with 39 % (11/28) in normal, 38% (14/37) in BCH, 27 % (3/11) in DYS and 14 % (1/7) in SCC.CONCLUSION: PCNA could act as an indicator accurately reflecting the high proliferation status of fetal esophageal epithelium. p53 may play an important role in growth and differentiation of fetal esophageal epithelium. p21WAF-1 may have no physiological function in development of fetal esophageal epithelium.     

Expressions of PCNA, p53, p21WAF-1and cell proliferation in fetal esophageal epithelia： Comparative study with adult esophageal lesions from subjects at high-incidence area for esophageal cancer in Henan, North China

AIM: To characterize the expression of p53, p21WAF-1 and proliferation-cell-nuclear-antigen (PCNA) in fetal esophageal epithelia and to determine the role of these genes in proliferation of fetal and adult esophageal epithelial cells. METHODS: Immunohistochemical avdin-biotin peroxidase complex (ABC) method was applied to 31 cases of fetal esophageal specimens and 194 cases of adult esophageal specimens to detect the expression of p53, p21WAF-1 and PCNA in fetal and adult esophageal epithelia. RESISTS: Both the PCNA positive immunostaining cell number and PCNA positive immunostaining rate in fetal esophageal epithelia (5064-239) were significantly higher than those in adults, induding normal epithelia (2004-113) and epithelia with basal cell hyperplasia (BCH) (2864-150) (P&lt;0.05, ttest). However, the number of PCNA positive immunostaining cells in adult esophageal dysplasia (7194-389) and squamous cell cardnoma (SCC) (12614-545) was apparently higher than that in fetal esophageal epithelia (5064-239) (P&lt;0.05, tbest). The positive immunostaining rabe of P53 was 10 % (3/31) in fetal esophageal epithelia, which was significantly lower than that in adult normal esophageal epithelia (50 %), adult epithelia with basal cell hyperplasia (62 %), dysplasia (73 %) and squamous cell carcinoma (86 %) (P&lt;0.05, Fisher‘‘s exact test). No p21WAF-l positive immunostaining cells were observed in fetal esophageal epithelia. However, p21w~l positive immunost~ining cells wereobserved in adult esophagus with 39 % (11/28) in normal, 38% (14/37) in BCH, 27 % (3/11) in DYS and 14 % (1/7) in SCC. CONCLUSION: PCNA could act as an indicator accurately reflecting the high proliferation status of fetal esophageal epithelium, p53 may play an important role in growth and differentiation of fetal esophageal epithelium, p21WAF-1 may have no physiological function in development of fetal esophageal epithelium.     

食管黏膜凋亡增殖和p53表达的增龄变化与食管鳞癌的关系

目的探讨食管黏膜增殖凋亡和p53表达的增龄变化以及这些变化与食管鳞癌的关系。方法按年龄分层选择连续胃镜检查对象818例,男414例,女404例。分为青中年组（258例）、老年前期组（296例）和老年组（264例）,进行食管活组织检查,应用TUNEL法检测凋亡指数（AI）,免疫组化法检测增殖指数（PI）和p53表达。结果食管正常上皮→单纯增生→轻中重度异型增生→鳞癌的发展过程中,AI等级逐渐下降,PI等级和p53表达逐渐增高。在食管正常上皮中,AI等级青中年组〉老年前期组〉老年组;PI等级比较,老年前期组分别高于青中年组和老年组（P〈0.01）;p53表达在老年前期组和老年组均高于青中年组（P〈0.01）。非条件logistic回归分析,食管鳞癌独立危险因素为增龄、PI等级和p53表达。当食管黏膜PI等级明显增高伴p53阳性时,鳞癌检出率明显增高,轻中重度异型增生有增高趋势,老年人尤为突出。结论食管黏膜正常上皮随增龄出现增殖凋亡和p53表达变化,与食管黏膜癌变过程变化相似,老年人食管黏膜PI明显增高伴p53阳性可作为食管鳞癌和癌前病变进一步随访和筛查的线索。     

Cell proliferation,bcl-2, c-myc,p53 and apoptosis as indicators of different aggressiveness in small lymphocytic lymphoma (SLL)

Abstract: Cell proliferation activity, by MIB1 mAb, expression of bcl-2, c-myc and p53 gene proteins and apoptotic index (AI) were assessed in. 54 cases of SLL and compared to the morphological subtypes of this disorder, defined by Lennert on the basis of amount and distribution of small and larger activated lymphocytes as diffuse, tumor-forming and pseudofollicular subtypes (DS, TFS, PFS). MIB1 scores showed significant differences between DS, PFS and TFS (5.5%, 16.61% and 24.14%, respectively; p<0.0001). Worth noting, the MIB1 score did not differ significantly when comparing DS with the diffuse areas of PFS, or TFS with the pseudofollicles of PFS. The mean bcl-2 gene protein score was displayed to a high extent in all subtypes, but less extensively by larger activated lymphocytes that, conversely, expressed c-myc. MIB1 score correlated negatively with bcl-2 and positively with c-myc protein scores. These findings suggest that lymphocytes protected from apoptosis by bcl-2 would be exponed to cell activation and growth acceleration provided by c-myc. This condition would account for a different aggressiveness of morphologically activated subtypes, such as TFS and PFS with larger pseudofollicles. The survival analysis, performed in 23 cases, showed a trend of association of cell proliferation and c-myc expression with a more aggressive progression of the disease. Overexpression of p53 and apoptosis were found only in a minority of cases, unrelated to the subtypes. In conclusion, cell growth fraction, bcl-2 and c-myc assessement may be of help in predicting the aggressiveness of different subtypes of SLL. This approach should be most conveniently applied to PFS, which represents a continuum between DS and TFS, in order to distinguish, in this heterogeneous subtype, more indolent from more aggressive disorders.     

Hp感染与胃癌和癌前病变中p53、ras、c-myc基因表达的关系

目的研究幽门螺杆菌（Hp）感染与胃癌（GC）和癌前病变中p53、ras、c-myc基因表达的关系,以探讨其致病机制。方法用美兰和W-S特殊染色方法确定Hp感染,免疫组化SP法检测p53、ras、c-myc基因的表达。结果慢性萎缩性胃炎（CAG）、肠化生（IM）、异型增生（DYS）、GC的Hp感染率均高于慢性浅表性胃炎（CSG）（P均〈0.05）;p53、ras、c-myc基因在GC、DYS中的表达均高于CAG（P均〈0.05）,p53、ras基因在IM中的表达均高于CAG（P〈0.05）;IM中Hp阳性者的p53阳性表达率高于Hp阴性者（P〈0.05）,DYS、GC中Hp阳性者p53、ras、c-myc的表达率高于Hp阴性者（P均〈0.05）。结论Hp感染可能通过调节p53、ras、c-myc基因的表达而促进GC的发生。     

A preliminary study on ras protein expression in human esophageal cancer and precancerous lesions

INTRODUCTION The esophageal carcinoma is a common malignant tumor in Linzhou City (Linxian) of Henan Province in northern China. Although the etiology and natural history of esophageal carcinoma are not clear, a substantial amount of evidence has been provided to suggest that the development of human esophageal squamous cell carcinomas (SCC) is a multistage progressive process[1-4] An early indicator of abnormality in persons predisposed to esophageal SCC is an increased proliferation of esophageal epithelial cells,morphologically manifested as basal cell hyperplasia (BCH), and dysplasia (DYS), and carcinoma in situ, which could be considered precancerous lesions of esophageal SCC[1-4].     

低Se低VE诱导肝细胞凋亡及相关基因所起的作用

目的 研究低硒（Ｓｅ）低维生素Ｅ（ＶＥ）能否诱导大鼠肝细胞凋亡及相关基因ｐ５３、ｂｃｌ－２和ｃ－ｍｙｃ所起的作用。方法 以天然的和人工半合成的低Ｓｅ低ＶＥ饲料喂养大鼠１７周,采用末端脱氧核苷酸转移酶介导的缺口末端标记（ＴＵＮＥＬ）检测肝细胞凋亡,采用免疫组化法检测肝细胞ｐ５３、ｂｃｌ－２和ｃ－ｍｙｃ蛋白。结果 与补Ｓｅ和ＶＥ组大鼠相比,低Ｓｅ低ＶＥ组大鼠肝细胞凋亡显著增加;ｐ５３和ｃ－ｍｙｃ蛋白增     

Localisation of apoptosis and expression of apoptosis related proteins in the synovium of patients with rheumatoid arthritis.

OBJECTIVES: To investigate whether apoptosis occurs in the synovium of rheumatoid arthritis (RA), and the intermediate molecules operating in this process. METHODS: DNA fragmentation was detected by in situ nick end labelling (ISNEL) in the synovium of patients with RA (n = 11) and control patients with femoral neck fracture (n = 5). The expression of proteins p53, p21WAFI/CIPI, c-myc, proliferating cell nuclear antigen (PCNA), and Bcl-2 was also examined by immunohistochemistry. RESULTS: ISNEL positive synovial cells with apoptosis specific morphology were detected in extremely limited areas in only two RA synovial tissue specimens. Proteins p53, p21WAFI/CIPI, and c-myc, known inducers of apoptosis or cell cycle arrest or both, were expressed in the sublining cells independent of ISNEL positive cells. PCNA, a marker for cell proliferation, was observed in the synovial lining cells. Bcl-2, an inhibitor of apoptosis, was expressed mainly in infiltrated lymphocytes and in parts of the sublining layer cells of RA; it also did not correspond with ISNEL staining. CONCLUSIONS: Our findings indicate that RA synovial cells undergo apoptosis in addition to cell proliferation, but the frequency of apoptosis was very low. We suspect that the apoptotic process in the RA synovium may be suppressed by over-expression of Bcl-2. Although expressed proteins p53, p21WAFI/CIPI, and c-myc were present in the RA synovium, these protooncogenes are probably not implicated in the apoptotic process.     

The role of XPB in cell apoptosis and viability and its relationship with p53, p21 and c-myc in hepatoma cells

BACKGROUND: Accumulation of DNA damage has been implicated in hepatocarcinogenesis. XPB plays a pivotal part in repairing damaged DNA. However, up to now, the biological effect of XPB on hepatoma cells remains elusive. MATERIALS AND METHODS: Here, we investigated the role of XPB in the apoptosis and the viability of hepatoma cells by using the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labelling and cell viability assay; we also investigated their relationship with p53, p21(waf1/cip1) and c-myc by using the RT-PCR and Western blot. RESULTS: Compared with the control cells HepG2/pcDNA3.1 or HepG2, XPB-transfected HepG2 cells (HepG2/pcDNA3.1-XPB) displayed lower viability, weaker activity and higher apoptosis index. At the same time, an increased expression of p21(waf1/cip1) mRNA, protein and p53 protein in addition to a decreased expression of c-myc mRNA and protein were detected in HepG2/pcDNA3.1-XPB cells. CONCLUSIONS: Our results indicated that XPB could inhibit the proliferation of hepatoma cells and had a positive effect on the expression of p53 and p21(waf1/cip1) but a negative effect on c-myc.     

c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle.

We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. This effect was associated with a loss of the G1 specificity of p53-mediated cell cycle arrest. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. Coexpression of bcl-2 and c-myc can totally overcome p53-induced apoptosis and cell cycle arrest by altering the subcellular trafficking of p53 during the cell cycle: the p53 remains in the cytoplasm of the cotransfected cells during a critical period in G1. This finding suggests a mechanism by which normal hematopoietic progenitors can survive and proliferate despite p53 expression and by which the inappropriate expression of bcl-2 and c-myc can cooperate in transformation.     

p21(Waf1/Cip1) regulates proliferation and apoptosis in airway epithelial cells and alternative forms have altered binding activities

p21(Waf1/Cip1) plays central roles in proliferation, differentiation, and apoptosis. Alterations in the expression and subcellular localisation of p21 occur during several lung diseases but the roles of p21 in the lung epithelium are unknown. The effects of p21 on proliferation and apoptosis in mouse airway epithelial cells (AECs) were examined using p21-null mice. AECs isolated from p21-null mice had increased proliferation and apoptotic rates compared to AECs from wild-type mice. Alterations in the subcellular localization of the cell cycle regulatory proteins p27, PCNA, and p53 were also evident in p21(-/-) cells. The nuclear and cytoplasmic forms of p21 present in AECs were also examined. Full-length p21 (20 kDa) was detected in nuclear fractions but a C-terminal truncated form (17 kDa) of p21 was present in cytoplasmic fractions. The binding activities of truncated p21 were altered compared to full-length p21. Although the latter was complexed with PCNA, Cdk2, Cdk4, Cdk6, cyclin D3, and cyclin E, truncated p21 was bound only to Cdk4 and cyclin D3. In conclusion, p21 regulates proliferation and protects against apoptosis in AECs. In addition, different forms of p21 are present in AECs and the subcellular localization of these forms reflects differences in p21 activity.     

Changes of TGFβ1 and TGFβRII expression in esophageal precancerous and cancerous lesions: a study of a high-risk population in Henan, northern China

The level of transforming growth factor beta1 (TGFbeta1) and transforming growth factor betaII receptor (TGFbetaRII) was determined immunohistochemically in normal tissues and tissues with different severities of lesions (basal cell hyperplasia, BCH; dysplasia, DYS; carcinoma in situ, CIS; and squamous cell carcinoma, SCC) from surgically resected human esophagi and esophageal biopsies of symptom-free subjects. The samples were from an area with high esophageal cancer incidence in northern China (Linzhou, formerly Linxian, and nearby county Huixian in Henan Province). Peroxidase immunostain (ABC) and conventional hematoxylin and eosin stain were used. The tissue sections were incubated with antibodies of TGFbeta1 and TGFbetaRII overnight. The immunoreactivity was observed in cytoplasm of the esophageal specimen. From normal to BCH to DYS to CIS and to SCC, the positive immunostaining rates for TGFbeta1 increased significantly (P < 0.05). A linear correlation between the positive immunostaining rates of TGFbeta1 and the different lesions was observed (P < 0.05). From well- to moderately- and poorly differentiated SCC, the positive immunostaining rates for TGFbeta1 decreased gradually, but the difference was not significant (P > 0.05). In contrast, with the lesions progressing from normal to BCH to DYS to CIS and to SCC, the positive immunostaining rates for TGFbetaRII decreased significantly (P < 0.05). From well- to moderately- and poorly differentiated SCC, the positive immunostaining rates for TGFbetaRII decreased significantly (P < 0.05). There was a linear correlation between the positive rates of TGFbetaRII and different lesions and SCC differentiation (P < 0.05). The present results indicated that the alterations of TGFbeta1 and TGFbetaRII is a frequent event in esophageal multistage carcinogenesis, the absent or lower expression of TGFbetaRII may lead to the loss of cell proliferation control by TGFbeta1 and the overexpression of TGFbeta1 may be a negative feedback response caused by the lower expression of TGFbetaRII protein.     

Bcl-2, p53 and c-myc expression in juvenile dermatomyositis

OBJECTIVE: To investigate p53, bcl-2 and c-myc expression in muscle biopsies from children affected with juvenile dermatomyositis (JDM) and to verify a possible dysregulation of programmed cell death in this autoimmune disease. METHODS: Ten muscle biopsies of children affected with JDM were formalin fixed and paraffin embedded. After haematoxylin and eosin staining, immunohistochemistry was performed employing monoclonal antibodies, anti-p53, anti-bcl-2 and anti-myc. Two normal muscle biopsies were studied as controls. RESULTS: In the biopsies of JDM, two different patterns of myofibers damage were observed: the first, with zones characterised by necrosis; and the second, with zones where an apoptotic process was dominant. Immunoreactivity for bcl-2 was positive in 8 out of 10 biopsies. P53 and c-myc expression were not present in any case. No relationship between the degree of bcl-2 immunostaining and the disease course or outcome was observed. CONCLUSIONS: The over-expression of bcl-2 protein in JDM may suggest a dysregulation of apoptosis in myofibers. Further studies are required in order to better understand the role of our data in the pathogenetic pathways of the disease.     

动脉粥样硬化斑块中细胞凋亡及其相关基因的表达

目的 :研究动脉粥样硬化 (AS)病灶中细胞凋亡的发生情况及其相关基因的表达情况 ,探讨细胞凋亡与bcl 2、p5 3、C myc基因表达的内在联系。方法 :选择因AS住院手术患者 2 0例作为研究对象〔其中男 17例 ,女 3例 ,平均年龄 (6 6 .8± 9.86 )岁 ,主要取患者的股动脉〕 ,及因意外伤害手术患者的 10例〔其中男 8例 ,女 2例 ,平均年龄 (5 1.6± 11.97)岁〕作为正常对照。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记 (TUNEL)技术检测两组动脉标本的细胞凋亡情况 ,采用免疫组化的方法检测bcl 2、p5 3及C myc基因的表达情况 ,应用透射电镜进行两组动脉标本的细胞形态学观察。结果 :AS病灶中 ,细胞凋亡的发生率明显高于正常对照血管 (P <0 .0 1) ,bcl 2蛋白的表达明显降低 ,p5 3蛋白及C myc蛋白的表达明显升高 (P <0 .0 1) ;透射电镜证实AS病灶中有大量的平滑肌细胞发生凋亡。结论 :细胞凋亡是AS病灶中细胞死亡的一种主要形式 ,bcl 2、p5 3及C myc基因的表达可能对细胞凋亡的发生起重要的调控作用。     

Loss of heterozygosity in multistage carcinogenesis of esophageal carcinoma at high-incidence area in Henan Province, China

AIM:Microsatellites are the repeated DNA sequences scattered widely within the genomes and closely linked with many important genes. This study was designed to characterize the changes of microsatellite DNA loss of heterozygosity (LOH) in esophageal carcinogenesis. METHODS: Allelic deletions in 32 cases of matched precancerous,cancerous and normal tissues were examined by syringe microdissection under an anatomic microscope and microsatellite polymorphism analysis using 15 polymorphic markers on chromosomes 3p, 5q, 6p, 9p, 13q, 17p, 17q and 18q. RESULTS: Microsatellite DNA LOH was observed in precancerous and cancerous tissues,except D9S1752. The rate of LOH increased remarkably with the lesions progressed from basal cell hyperplasia (BCH) to squamous cell carcinoma (SCC) (P<0.05).Three markers,D9S171, D13S260 and TP53, showed the highest incidence of LOH (>60%).LOH loci were different in precancerous and cancerous tissues. LOH in D3S1234 and TP53 was the common event in different lesions from the same patients. CONCLUSION: Microsatellite DNA LOH occurs in early stage of human esophageal carcinogenesis, even in BCH. With the lesion progressed, gene instability increases, the accumulation of this change may be one of the important mechanisms driving precancerous lesions to cancer.     

Establishment of a near-triploid human B-cell lymphoma cell line with t(14;18) and a p53 gene point mutation

We report a rare large B-cell non-Hodgkin's lymphoma having a characteristic near-triploid cell population with add(17)(p22) and t(14;18)(q32;q21) translocation. We also established and characterized a new cell line (TK cell) derived from the present lymphoma. A codon 180 mutation (GAG --> GAT) in the p53 gene was detected. t(14;18)(q32;q21) was revealed juxtaposition of the bcl-2 and JH genes. Immunoprecipitation analyses of p53 and bcl-2 revealed that abnormality of the p53 protein and aberrant bcl-2 expression, which may protect cells from apoptosis, may be critical to the development of leukaemogenesis exhibiting near-triploid chromosomes.