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>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     

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.     

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.     

Apoptosis and its relationship with cell proliferation, p53, Waf1p21, bcl-2 and c-myc in esophageal carcinogenesis studied with a high-risk population in northern China

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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.     

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].     

IKKβ和NF-κB p65在食管癌及癌前病变中的表达

目的探讨IKKβ和NF-κBp65在食管癌和癌前病变组织中的表达及意义。方法采用免疫组化PV-9000法检测正常食管上皮、基底细胞增生、间变和鳞状细胞癌中IKKβ和NF—κBp65的表达情况,以及在食管癌不同分化、淋巴结转移、浸润程度中的表达情况。结果IKKβ、NF—κBp65在不同组织中阳性表达率分别为：正常上皮（19．7％／12．8％）、基底细胞增生（46．7％／43．3％）、间变（76．0％／64．0％）和鳞状细胞癌（84．8％／75．8％）,且随着食管病变进展,阳性表达率明显升高,正常上皮与鳞状细胞癌之间有明显差异（P〈0．05）;IKKβ、NF—κBp65的表达与食管癌组织的淋巴结转移和浸润程度呈正相关（P〈0．05）。结论IKKβ、NF—κBp65在食管癌和癌前病变表达激活,可能与食管癌的发生发展及转移浸润密切相关。     

Autoantibody detection to tumor‐associated antigens of P53, IMP1, P16, cyclin B1, P62, C‐myc,Survivn, and Koc for the screening of high‐risk subjects and early detection of esophageal squamous cell carcinoma

The aim of this study was to evaluate the diagnostic values by detecting sera autoantibodies to eight tumor‐associated antigens (TAAs) of P53, IMP1, P16, cyclin B1, P62, C‐myc, Survivn and Koc full‐length recombinant proteins for the screening of high‐risk subjects and early detection of esophageal squamous cell carcinoma (ESCC). Enzyme‐linked immunosorbent assay was used to detect autoantibodies against the eight selected TAAs in 567 sera samples from four groups, including 200 individuals with normal esophageal epithelia (NOR), 214 patients with esophageal basal cell hyperplasia (BCH), 65 patients with esophageal dysplasia (DYS), and 88 patients with ESCC. In addition, the expression of the eight antigens in esophageal tissues was analyzed by immunohistochemistry. Statistically significant distribution differences were identified among the four groups for each of the individual autoantibodies to six TAAs (P53, IMP1, P16, cyclin B1, P62, and C‐myc); the detection rates of antoantibodies were positively correlated with the progression of ESCC. When autoantibody assay successively accumulated to six TAAs (P53, IMP1, P16, cyclin B1, P62, and C‐myc), a stepwise increased detection frequency of autoantibodies was found in the four sera groups (6% in NOR, 18% in BCH, 38% in DYS, and 64% in ESCC, respectively), the risks to BHC, DYS, and ESCC steadily increased about 3‐, 9‐, and 27‐folds. The sensitivity and the specificity for autoantibodies against the six TAAs in diagnosing ESCC reached up to 64% and 94%, respectively. The area under the receiver operating characteristic curve for the six anti‐TAA autoantibodies was 0.78 (95% confidence interval 0.74–0.83). No more increasing in sensitivity was found with the addition of new anti‐TAA autoantibodies. A combination detection of autoantibodies to TAAs might distinguish ESCC patients from normal individuals and the patients with esophageal precancerous lesions.     

Tumor suppressor gene p16 and Rb expression in gastric cardia precancerous lesions from subjects at a high incidence area in northern China

AIM:To further understand the molecular basis for gastric cardia carcinogenesis and to provide etiological clues.METHODS:Endoscopic mucosa biopsy and histopatthological examinations were made on 37 subjects from a high incidence area for both esophageal and gastric cardia carcinomas in northern China .All the biopsy samples were fixed in 850ml^-1,L alcohol and embedded in paraffin.Each block contained one piece of tissue and was serially section at 5 μm,Immunohistochemistyr(ABC)was carried out on these gastric cardia samples to detemine the alteations of p16 and Rb.RESULTS:Based on the histopathlogical examination there were 11 cases of chronic superficial gastritis,12 cases of chronic atrophic gastritis and 14 cases of dysplasia.The immunostaining demonstrated different levels of unclear immunostaining of p16 and Rb in nomal gastric Cardia tissue and the tissues with different severity of lesions .With the lesions progressing.the positive immunostaining rates for p16 protein had a decreasing tendency.In contrast,the positive immunostaining rate for Rb protein had an increasing tendency.There was a significant negative relationship between the two parameters,Changes of p16 was CSG 11(100%),CAG7(58%),DYS4(29%),and changes of Rb was CSG2(18%),CAG8(67%)and DYS12 (86%),(P&lt;0.05). CONCLUSION：The alterations of p16 and Rb protein may play a role in the early stages of gastric cardia carcinogenesis.     

Expression of ornithine decarboxylase in precancerous and cancerous gastric lesions

AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG,n = 32),chronic atrophic gastritis CAG,n = 43; 15 with and 28 without intestinal metaplasia (IM),gastric dysplasia (DYS,n = 11) and gastric cancer (GC,n = 48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. METHODS: The positive rate of ODC expression was 34.4%,42.9%,73.3%,81.8% and 91.7% in cases with CSG,CAG without IM,CAG with IM,DYS and GC,respectively (P < 0.01),The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally,GC. In addition,ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P < 0.05). CONCLUSION: The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.     

An increased transforming growth factor beta receptor type I:type II ratio contributes to elevated collagen protein synthesis that is resistant to inhibition via a kinase-deficient transforming growth factor beta receptor type II in scleroderma

OBJECTIVE: Aberrant transforming growth factor beta (TGFbeta) signaling has been implicated in the pathogenesis of scleroderma (systemic sclerosis [SSc]), but the contribution of specific components in this pathway to SSc fibroblast phenotype remains unclear. This study was undertaken to delineate the role of TGFbeta receptor type I (TGFbetaRI) and TGFbetaRII in collagen overexpression by SSc fibroblasts. METHODS: Primary dermal fibroblasts from SSc patients and healthy adults were studied (n = 10 matched pairs). Adenoviral vectors were generated for TGFbetaRI (AdTGFbetaRI), TGFbetaRII (AdTGFbetaRII), and kinase-deficient TGFbetaRII (AdDeltakRII). TGFbetaRI basal protein levels were analyzed by (35)S-methionine labeling/immunoprecipitation and immunohistochemistry. Type I collagen and TGFbetaRII basal protein levels were analyzed by Western blot and newly secreted collagen by (3)H-proline incorporation assay. RESULTS: Analysis of endogenous TGFbetaRI and TGFbetaRII protein levels revealed that SSc TGFbetaRI levels were increased 1.7-fold (P = 0.008; n = 7) compared with levels in healthy controls, while TGFbetaRII levels were decreased by 30% (P = 0.03; n = 7). This increased TGFbetaRI:TGFbetaRII ratio correlated with SSc collagen overexpression. To determine the consequences of altered TGFbetaRI:TGFbetaRII ratio on collagen expression, healthy fibroblasts were transduced with AdTGFbetaRI or AdTGFbetaRII. Forced expression of TGFbetaRI in the range corresponding to elevated SSc TGFbetaRI levels increased basal collagen expression in a dose-dependent manner, while similar TGFbetaRII overexpression had no effect, although transduction of fibroblasts at higher multiplicities of infection led to a marked reduction of basal collagen levels. Blockade of TGFbeta signaling via AdDeltakRII resulted in approximately 50% inhibition of basal collagen levels in healthy fibroblasts and in 5 of 9 SSc cell lines. A subset of SSc fibroblasts (4 of 9 cell lines) was resistant to this treatment. SSc fibroblasts with the highest levels of TGFbetaRI were the least responsive to collagen inhibition via DeltakRII. CONCLUSION: This study indicates that an increased TGFbetaRI:TGFbetaRII ratio may underlie aberrant TGFbeta signaling in SSc and contribute to elevated basal collagen production, which is insensitive to TGFbeta signaling blockade via DeltakRII.     

CD44 V6和MMP-9在胃癌及癌前病变组织中表达

目的探讨CD44V6和基质金属蛋白酶9（MMP-9）在胃癌及癌前病变组织中表达。方法免疫组化SP法测定正常胃黏膜（NOR）、萎缩性胃炎伴中重度肠化（IM）、萎缩性胃炎伴中重度不典型增生（DYS）和早期胃癌（EGC）各40例，进展期胃癌（AGC）100例中CD44V6和MMP-9的表达。结果NOR、IM、DYS、EGC和AGC组中，分别有0、15．0％、25．0％、45．0％和72．0％CD44V6阳性，0、40．0％、50．0％、40．0％和68．0％MMP-9阳性。从IM、DYS至EGC和AGC组，CD44V6和MMP-9表达渐增（均P〈0．05）。结论CD44V6、MMP-9在胃痛的演变过程中不仅仅参与了浸润转移．其在胃癌早期发生、发展中也起着重要作用。     

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.     

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。     

Epstein-Barr virus association is rare in esophageal squamous cell carcinoma

Background. A critical role of Epstein-Barr virus (EBV) in carcinogenesis of nasopharyngeal squamous cell carcinoma and gastric adenocarcinoma is strongly suspected. We analyzed the possible EBV association for Japanese squamous cell carcinoma (SCC)-dominant esophageal cancer cases. Methods. We retrospectively screened 36 surgically resected esophageal cancer lesions from 36 patients maily with SCC using in situ hybridization (ISH) for EBV-encoded small RNA1 (EBER-1). EBV DNA analysis using real-time quantitative polymerase chain reaction (Q-PCR) was performed for three recent cases. Results. We found no EBER-1-positive cancer cell in any tested esophageal cancer lesion. There were many EBER-1-positive tumor-infiltrating lymphocytes in the basaloid SCC lesion and a small number of positive lymphocytes in the other five advanced SCC lesions (14.7% of SCC). One SCC lesion with a highcopy number of EBV DNA had EBER-1-positive lymphocytes. Conclusions. EBV is rarely associated with esophageal SCC, and may appear through tumor-infiltrating lymphocytes in some advanced lesions.     

Transforming growth factor-beta receptor types I and II in cultured porcine leydig cells: expression and hormonal regulation

The steroidogenic activity of testicular Leydig cells is controlled both by the pituitary hormone (LH) and by growth factors such as transforming growth factor-beta peptides (TGFbeta1, -2, and -3; inhibin/activin; and anti-Mullerian hormone). By using primary cultures of porcine Leydig cells as a model, the aim of the study was to identify and characterize the TGFbeta receptors and to study their regulation by LH/hCG. TGFbeta receptors have been identified and characterized through three different approaches, including cross-linking experiments and Western and Northern blotting analyses. In cross-linking experiments, labeled TGFbeta was shown to bind to three different molecular species of 300, 80, and 53 kDa, which may correspond to the protein betaglycan (also known as TGFbeta type III receptor) and TGFbeta type II and I receptors (TGFbetaRII and TGFbetaRI), respectively. The presence of TGFbetaRI and -RII was further demonstrated by Western blotting analysis using specific polyclonal antibodies. Finally, the expression of betaglycan, TGFbetaRII, and TGFbetaRI messenger RNAs, was confirmed by Northern blotting analysis, as shown by the presence of 6.4-, 4.6-, and 5.8-kb messenger RNAs, respectively. By using a RT-PCR approach, the mediators of the TGFbeta signal, Smads 1-7, were also detected in cultured Leydig cells. TGFbetaRI and TGFbetaRII protein levels were enhanced by hCG/LH in a dose-dependent (maximal effect with 0.3 ng/ml hCG) and time-dependent (maximal effect observed after 48 h of hCG treatment) manner. Furthermore, to determine whether the stimulatory effect of LH/hCG was mediated by testosterone, use was made of aminogluthetimide, an inhibitor of cytochrome P450scc. The inhibition oftestosterone formation did not affect the stimulatory effect of LH/hCG on TGFbetaRI and -RII levels, suggesting that the gonadotropin action is not mediated by the steroid hormone. Together, the present findings demonstrate that the TGFbeta receptors are expressed and are under hormonal (gonadotropin) control in cultured porcine Leydig cells.     

Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program

AIM To determine the association of p53, carcinoembryonic antigen(CEA) and CA19-9 protein expression with esophageal carcinogenesis.METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia(BCH), 247 with low-grade dysplasia(LGD), 51 with high-grade dysplasia(HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROCcurve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions.RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH.CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.