食管癌发生发展过程中COX-2蛋白表达的研究

目的研究环氧合酶-2(COX-2)蛋白在食管癌及癌前病变组织中的表达,探讨其在食管癌发生、发展过程中的作用。方法应用免疫组织化学方法检测43例鳞状细胞癌及22例增生性病变(单纯增生8例,轻、中、重度不典型增生分别6、4、4例)和6例正常食管黏膜鳞状上皮的食管组织中COX-2蛋白的表达情况。结果正常食管黏膜上皮、单纯性增生和轻/中度不典型增生未发现COX-2蛋白表达;25%(1/4)重度不典型增生、74%(32/43)食管鳞状细胞癌中COX-2蛋白表达阳性。COX-2蛋白表达I-II期强阳性率为40%(4/10),III-IV期为73%(10/22);COX-2蛋白的表达与淋巴转移、浸润深度、肿物大小无关。结论 COX-2蛋白的表达与食管癌的发生发展关系密切,是食管癌发生发展中的一个重要指标。     

卢戈液染色与p53蛋白检测诊断早期食管癌的可行性研究

目的　验证内镜下卢戈液染色和活组织p5 3检测 ,诊断食管早期癌和表浅癌的可行性。方法　将 97例食管癌手术标本先用卢戈液染色 ,然后对粘膜不着色区行p5 3蛋白免疫组化染色。结果　共有 6 3处直径大于 2mm的粘膜不着色区 ,其中正常粘膜 2处 ,单纯增生 7处 ,不典型增生 42处 ,原位癌 1处 ,鳞状细胞癌 11处 ;p5 3蛋白的阳性表达主要发生在重度不典型 (42 3% )和鳞状细胞癌 (45 5 % )的细胞核内 ,而在正常粘膜、单纯增生和轻至中度不典型增生组织中几乎无表达 (P <0 0 5 )。结论　内镜下卢戈液染色和活组织p5 3检测诊断食管早期癌和表浅癌的设想具有可行性。     

乳腺不典型增生和乳腺癌中p53、ER表达的意义

目的探讨p53基因产物和雌激素受体(ER)在乳腺不典型增生和乳腺癌中表达及意义。方法用ABC免疫组化法检测乳腺不典型增生和乳腺癌细胞p53基因产物和ER表达。结果乳腺上皮不典型增生Ⅰ级者上皮细胞ER染色结果与正常乳腺上皮细胞相似，不典型增生Ⅱ级ER表达明显增强，22／24例阳性，不典型增生Ⅲ级20／22例见ER染色阳性。在乳腺上皮不典型增生Ⅰ级无p53蛋白表达，不典型增生Ⅱ级、Ⅲ级中分别有3／24和7／22例p53蛋白表达。乳腺癌59例，ER阳性率为36／59(61．02％)。乳腺癌p53蛋白表达阳性22／59(37．29％)。结论p53可促进正常细胞以不典型增生向癌的转化，ER对不典型增生癌变起重要的刺激、激活作用。p53-／ER 代表正常组织、良性增生与高分化和好的预后，p53 ／ER-多为不典型增生、低分化癌和差的预后。所以同时检测p53、ER对判断不典型增生向癌的转化及乳腺癌患者的预后有重要意义。     

P53蛋白与增殖细胞核抗原在食管、贲门癌中的表达及临床意义

目的 为了探讨P53蛋白和增殖细胞核抗原在食管、贲门癌中的表达及其临床意义.方法 应用SP免疫组织化学法,研究了40例食管鳞状细胞癌和28例贲门腺癌P53蛋白的表达及其与细胞增殖活性、淋巴结转移的关系.结果 食管癌与贲门癌P53蛋白阳性率分别是60%和57.1%.53.3%的癌旁组织中有P53蛋白过度表达.食管癌有淋巴结转移者P53蛋白阳性率和细胞增殖活性较无转移者明显增高(P＜0.01),说明p53基因的突变以及导致细胞恶性增殖不仅与食管、贲门癌的发生有关,而且在其淋巴结转移中也起重要作用.结论 检测P53蛋白和细胞增殖核抗原对食管、贲门癌的早期诊断及判断肿瘤的恶性程度,评估预后有较高的参考价值.     

Src家族酪氨酸激酶Fyn在人食管鳞状细胞癌中的表达

目的 探讨食管鳞状细胞癌组织中Fyn的表达水平及其意义.方法 收集13例食管鳞状细胞癌组织(ESCC)和10例食管正常黏膜上皮组织(UNR),采用免疫组织化学法和免疫印迹法分析食管鳞状细胞癌组织及食管正常黏膜组织Fyn蛋白表达水平的变化.结果 免疫组织化学染色显示食管鳞状细胞癌组织中Fyn蛋白表达水平(9.68±2.31)高于食管正常黏膜组织中染色指数(3.21±1.25),差异有统计学意义(P<0.01).免疫印迹结果亦显示食管鳞癌组织中Fyn蛋白表达强于食管正常黏膜组织.结论 Fyn蛋白在食管鳞状细胞癌组织中高表达,提示Fyn基因在食管鳞状细胞癌的发生发展过程中可能起重要作用.     

食管癌早期诊断对手术方式的影响

目的探讨食管癌早期诊断对手术方式的影响。方法对3 000名年龄41⁶9岁的农村健康成年人人群进行早期食管癌筛查。行胃镜检查后,内镜退至食管时进行2%卢氏碘染色,并对浅染色和不染色的黏膜进行活检,送病理检查。结果在3000人被检查对象中,查出食管黏膜轻度不典型增生700例,中度不典型增生6例。筛查出需要治疗的阳性患者共9例,其中食管黏膜中度不典型增生1例,食管黏膜高级别上皮内瘤变3例,食管黏膜鳞状细胞癌5例,其中,有3例黏膜病变<2 cm,2例黏膜病变>2 cm。在9阳性患者中,4例患者已经在上级医院行内镜下手术治疗。结论筛查并诊断出早期食管癌患者,可以选择内镜下手术治疗,减轻患者痛苦及经济负担,提高生存时间。     

内镜黏膜下隧道法切除早期食管癌及癌前病变的应用分析

目的 探讨内镜黏膜下隧道法在切除早期食管癌及癌前病变中的应用价值.方法 17例术前超声内镜检查判断病变局限于黏膜层,经黏膜活检发现食管上皮局灶癌变或重度不典型增生的患者,采用黏膜下隧道法的内镜下早期癌切除.结果 17例中,术后病理确诊鳞状上皮增生伴黏膜慢性炎4例,重度不典型增生5例,高至中分化鳞癌8例,其中T1a期7例,T1b期1例.有2例切除黏膜边缘重度不典型增生,1例黏膜下层切缘见癌细胞,其余病例均病灶完整切除.术后1例患者因迟发性出血转开胸手术治疗,其余患者均恢复良好.结论 黏膜下隧道法切除黏膜内早期食管癌及癌前病变安全、有效,更符合直视、充分暴露的外科原则,明显减少出血、穿孔的并发症风险,但其对病灶切除范围判断有一定困难,需在手术中充分注意.     

水通道蛋白4在食管鳞癌中的表达

目的 观察水通道蛋白4(AQP4)在食管鳞癌组织中的表达并探讨其在食管癌发病中的作用.方法 取食管鳞癌组织、癌旁正常鳞状上皮组织各16例,应用免疫组织化学,逆转录.聚合酶链反应(RT-PCR)技术检测AQP4的表达及分布.结果 免疫组织化学显示,AQP4表达于正常食管黏膜鳞状上皮细胞,在食管鳞癌组中主要表达于肿瘤上皮细胞和癌巢中.RT-PCR法结果 显示,AQP4在癌旁正常组织和食管癌组织中的mRNA表达平均相对A值分别为0.45±0.12、0.70±0.23,差异有统计学意义(P＜0.05).结论 AQP4在正常食管黏膜鳞状上皮细胞以及食管鳞癌组中均有表达,而且在癌组织中表达增加;AQP4可能对人食管癌的发生、发展起促进作用.     

食管鳞状细胞癌组织中酪氨酸激酶受体B和脑源性神经生长因子蛋白及mRNA的表达及意义

目的 探讨酪氨酸激酶受体B( TrkB)和脑源性神经生长因子(BDNF)蛋白及mRNA在食管鳞状细胞癌(ESCC)组织中的表达及其意义.方法 应用免疫组织化学及原位杂交法检测59例ESCC、27例癌旁不典型增生组织及36例正常食管黏膜组织中TrkB和BDNF蛋白及mRNA的表达.结果 ESCC组织中TrkB蛋白及mRNA的阳性表达率分别为71.2％和64.4％,显著高于癌旁不典型增生组织(阳性率分别为48.1％和33.3％)及正常食管黏膜组织(阳性率均为0.0％),组间比较差异有统计学意义(P＜0.05);此外,BDNF蛋白和mRNA在ESCC组织中的阳性表达率分别为76.3％和69.5％,也显著高于癌旁不典型增生组织(阳性率分别为55.6％和40.7％)及正常食管黏膜组织(阳性率均为0.0％),组间比较差异有统计学意义(P＜0.05).TrkB和BDNF蛋白及mRNA的表达均与ESCC的分化程度、浸润深度和淋巴结转移密切相关(P＜0.05).进一步相关分析结果显示,TrkB mRNA和蛋白的表达均与BDNF mRNA和蛋白的表达呈正相关(P＜0.05).结论 TrkB和BDNF蛋白及mRNA表达与ESCC的发生、发展和转移密切相关.     

STAT3在食管鳞状细胞癌中的表达和意义

目的研究STAT3蛋白表达与食管鳞状细胞癌临床病理特征的关系,探讨其在食管癌变中的可能作用。方法应用免疫组织化学S-P法检测60例食管鳞状细胞癌及其癌旁组织中STAT3蛋白的表达,结合临床资料进行分析。结果STAT3蛋白阳性反应主要定位于胞质。食管鳞状细胞癌组织中STAT3蛋白表达阳性率86.7%(平均灰度值为36.05±13.74)明显高于正常组织阳性率17.6%(平均灰度值为16.92±5.43)(P<0.05)。STAT3蛋白在低分化、中分化、高分化鳞癌组的阳性表达率分别是100%、95%、73.08%,平均灰度值分别是51.22±7.09、42.18±7.21、23.16±6.94,3组间差异有统计学意义(P<0.01)。肿瘤分化程度越高STAT3蛋白表达越低。有淋巴细胞转移的食管癌组织中STAT3表达的阳性率100%(平均灰度值45.36±10.36),明显高于无淋巴细胞转移的食管癌组织阳性率78.38%(平均灰度值30.26±12.41)(P<0.05)。结论STAT3蛋白在食管鳞状细胞癌组织中的高表达可能与食管鳞癌的发生有关系。     

Immunohistochemical Expression of P53and Oncogenes in Ulcerative Colitis-associated ColorectalCarcinoma

The role of the tumor suppressor gene p53and proto-oncogenes mdm-2, waf-1,and bcl-2 in sporadic colorectal carcinoma (CRC) hasbeen well investigated. However, little is known about the role ofthese genes in the development of ulcerative colitis-associatedcolorectal carcinoma (CAC). Colectomy specimens from patients with CAC,patients with ulcerative colitis (UC) and dysplasia, patients withlong-standing UC without carcinoma or dysplasia, and patients with CRC were investigated in comparison to normal colon (NC) specimens frompatients with diverticulosis without histologic signs of inflammation.Immunohistochemistry was performed with antibodies against p53, mdm-2,waf-1, and bcl-2; and staining was evaluated semiquantitatively with anexpression of more than 20% of tumor cell nuclei or epithelial cellnuclei in nontumor specimens considered "positive." Statisticalanalysis was performed using Fisher’s exact test. In carcinomas, p53 was positive in 50% of CRC tissues and 60% of CACtissues without statistical difference. Positive expression of p53 was found in most high-grade dysplasia but not inlow-grade dysplasia (p < 0.01). Whereas mdm-2 and bcl-2 were only sporadicallyexpressed, waf-1 was observed in most specimens, with ahigh prevalence in UC without carcinoma or dysplasia (11/15). NCspecimens were always negative for all antibodies. Immunohistochemicalexpression of p53, mdm-2, waf-1, and bcl-2 issimilar for CAC and CRC. The malignant potential of dysplasia in UC ispartially confirmed by a high prevalence of p53 and waf-1 expression, suggesting that CAC may develop alongpathways that are different from CRC. High expression ofwaf-1 in nonmalignant long-standing UC has to be provedover a long-term course in its role as an independent cancer riskfactor in UC patients.     

Expression of p53 protein related to human papillomavirus and DNA ploidy in superficial esophageal carcinoma

We examined the p53 protein and human papilloma virus (HPV) by immunohistochemistry and DNA ploidy by cytofluorometry in paraffin-embedded esophageal carcinoma tissue specimens. Sixty-one patients with superficial esophageal carcinoma were operated on between 1983 and 1991 without any prior treatment. Immunostaining of the anti-p53 protein antibody (CM1) was positive in 32 carcinomas (52%). Patients with p53-positive tumors had a poorer outcome than those with p53-negative tumors (P<0.05). In addition, patients with p53-positive tumors did not have any characteristic site of relapse. Only 5 of the 61 patients (8.2%) had HPV-positive tumors. One of these 5 carcinomas expressed both p53 protein and HPV. Three patients with HPV-positive tumors which had invaded the submucosal layer died of relapse. A determination of DNA ploidy revealed 30 patients with aneuploid tumors, 13 with polyploid tumors and 18 with diploid tumors. The outcome of the patients with aneuploid tumors was worse than that of the patients with diploid tumor (P<0.05). p53 protein expression was not associated with DNA ploidy; however, the 16 patients who had both p53-positive and aneuploid tumors had a worse prognosis than patients with p53-negative and aneuploid tumors (P<0.01). These findings suggest that p53 protein expression in conjunction with DNA ploidy may be a useful indicator in evaluating the prognosis of patients with superficial esophageal carcinoma.     

Reciprocal expression of bcl-2 and p53 oncoproteins in urothelial dysplasia and carcinoma of the urinary bladder

In order to investigate if and when the bcl-2 oncoprotein is activated in bladder tumorigenesis and its relationship with p53 overexpression and patient survival, we studied bcl-2 and p53 expression immunohistochemically in matched normal urothelium, dysplasia and cancer specimens selected by step-sectioning from 54 radically resected bladders for non-metastatic transitional cell carcinoma (TCC). In normal urothelium and mild dysplasia, bcl-2 was restricted to the basal cell compartment, while in moderate and severe dysplasia its expression was detectable also in the upper regions. Excess bcl-2 immunoreactivity was found in 27 (50%) of carcinomas, and a larger proportion of high-grade TCCs showed bcl-2 expression compared with that of low-grade TCCs (P < 0.05). Overexpression of p53 protein showed a increasing trend toward the progression of bladder tumorigenesis (P < 0.01) and a significant reciprocal correlation was found between bcl-2 and p53 expression in either various dysplasias (P < 0.01) or carcinoma (P < 0.05). With the evolution from mild dysplasia to carcinoma in individual cases, loss of bcl-2 expression was more frequently observed in superficial (P < 0.02) or low-grade carcinoma (P < 0.05) than in muscle-invasive or high-grade carcinoma. Furthermore, patients with negative immunostaining for both bcl-2 and p53 in cancer lesions had a significantly more favorable prognosis compared with those with positive immunostaining for the oncoproteins (P < 0.05), although bcl-2 by itself did not predict patient survival. We suggest that aberrant activated bcl-2, which is seen earlier than p53, appears to facilitate bladder tumorigenesis and to enhance tumor aggression in some extent. Received: 22 October 1997 / Accepted: 2 January 1998     

Esophageal squamous cell carcinomas and expression of p53, Bcl-2, and Bcl-X(L)

p53 protein promotes apoptosis, whereas Bcl-2 family proteins have an antiapoptotic function. This study determines the predictive value of selected clinical and histopathological factors in correlation with the expression of p53, Bcl-2, and Bcl-X(L) proteins in esophageal squamous cell carcinomas (SCCs). Paraffin-embedded sections from 19 surgically resected primary esophageal SCCs were examined by immunohistochemistry. p53 expression was related to degree of tumor differentiation (P = 0.044). Bcl-2 expression was associated with regional lymph node metastasis (P = 0.053), whereas Bcl-X(L) expression was correlated with distant metastasis (P = 0.060) and with the expression of Bcl-2 protein (P = 0.068). p53 and Bcl-2 family proteins may help to estimate the properties of esophageal SCCs and provide useful information to the oncologist for the selection of patients for intensive combined therapy modalities with curative intention or for palliative therapy.     

P53 accumulation in precursor lesions and early stages of bladder cancer

Summary Recent investigations have demonstrated alterations of the p53 tumor-suppressor gene in a considerable number of transitional-cell carcinoma (TCC) specimens. Thus far, these investigations have been restricted to either papillary TCC or invasive bladder cancer. To obtain further information on a possible involvement of p53 in bladder cancer development or tumor progression, investigations of precursor lesions and early stages of this disease are required. Immunohistochemical examination of 6 dysplasias and 24 carcinomas in situ (TIS) showed p53 accumulation, which is suggestive of p53 inactivation, in 2 (33%) and 9 (38%) of these specimens, respectively. This ratio was similar in 9 T1 lesions (33%) and in 14 cases of muscle-infiltrative disease (35%). In papillary tumors, p53 accumulation was observed exclusively in 3/10 moderately differentiated or high-grade lesions but not in 1 Ta G1 tumor. The expression of p53 accumulation was a consistent finding. The examination of tumor recurrences yielded either the presence or the absence of p53 overexpression in the primary and recurrent tumors of 7/8 patients. Similarily, in multifocal TCC, p53 accumulation was also either present or absent in 10/11 cases examined. These results suggest the existence of at least two different subgroups of TCC, with p53 accumulation being present in one of these groups. The observation of p53 accumulation in dysplasia and in TIS is a prerequisite for a possible involvement of p53 in bladder cancer carcinogenesis, although it does not prove this assumption.This study was supported by grant Schm 782/2-1 by the Deutsche Forschungsgemeinschaft (DFG)     

Expression of human epidermal growth factor and its receptor in esophageal cancer

The expression of human epidermal growth factor (hEGF) was examined immunohistochemically in 86 esophageal cancer lesions, comprising 67 primary tumors and 19 metastatic lymph nodes. In the normal esophagus, the parabasal and intermediate cell layers showed a weak expression of hEGF, however, hEGF-positive tumor cells were detected in 62 (92.5 per cent) of the 67 primary esophageal carcinomas and in 18 (94.7 per cent) of the 19 metastatic lymph nodes. In this study, the immunoreactivity of hEGF was classified into 4 grades according to the number of stained tumor cells. A significant correlation was observed between the histologic type and the grade of hEGF immunoreactivity (Chi-square test, p less than 0.01). hEGF immunoreactivity in well differentiated squamous cell carcinomas was significantly higher than in other squamous cell carcinomas, although there were no correlations between other pathological findings and hEGF immunoreactivity. Patients with hEGF immunoreactivities of grades II or III had much worse prognoses than those with grades 0 or I (p less than 0.05). In 22 esophageal carcinomas and 10 normal esophageal mucosae, EGF receptor (EGFR) contents were measured by the competitive binding assay. The average EGFR content (101.3 +/- 35.7 fmol/mg protein, mean +/- SE) of the esophageal carcinomas was significantly higher than that (5.3 +/- 1.2) of the normal esophageal mucosae (p less than 0.05). Moreover, in hEGF negative tumors, EGFR contents were lower than in hEGF positive tumors. These results suggest that hEGF and EGFR show increased production in squamous cell carcinomas and could to be useful prognostic factors in patients with esophageal cancer.