大肠腺瘤与腺癌P21,P53,P185蛋白表达及ras,p53基因突变的检测

应用免疫组化及ＰＣＲ－ＲＦＬＰ法检测３０例大肠腺瘤、７４例大肠腺癌及癌旁粘膜Ｐ２１、Ｐ５３、Ｐ１８５蛋白表达及ｒａｓ、ｐ５３基因突变。结果表明，大肠腺瘤Ｐ２１、Ｐ５３蛋白阳性率（５３．３％，２７．６％）高于癌旁粘膜（Ｐ＜０．０１），二者过度表达与腺瘤恶性倾向有关。大肠腺癌Ｐ２１、Ｐ５３及Ｐ１８５蛋白阳性率（７２．９％，３７．８％，４７．２％）皆高于腺瘤Ｉ级不典型增生（Ｐ＜０．０１，Ｐ＜０．０５及Ｐ＜０．０５）。９例腺瘤，４０例腺癌存在两种以上蛋白表达，共同表达与腺瘤恶性倾向及腺癌预后有关。大肠腺瘤及腺癌ｒａｓ基因突变率分别为２６．７％及４１．９％，ｒａｓ基因突变与腺瘤恶性倾向有关。大肠腺瘤及腺癌ｐ５３基因２４８位点突变率分别为３．３％及１４．９％。６例腺癌存在两种基因突变，两种基因协同突变与大肠癌预后有关。提示ｒａｓ、ｐ５３及ｃ－ｅｒｂＢ－２基因改变均参与了大肠癌的发生、发展过程。     

大肠肿瘤中抑凋亡基因bcl－2和p53蛋白产物的表达和意义

用免疫组化方法观察４５例大肠腺瘤和６１例大肠腺癌中ｂｃ１－２和ｐ５３蛋白的表达。结果显示：正常大肠粘膜中ｂｃ１－２和ｐ５３均未见表达，而大肠腺瘤及大肠腺癌阳性率均较正常组织明显增加（Ｐ＜０．０１）．大肠腺瘤中ｂｃ１－２表达位于不典型增生较重区域。大肠腺瘤ｐ５３表达随腺瘤直径增加而增加，其中≥２０ｍｍ组阳性率显著高于＜１０ｍｍ组（ｐ＜０．０５）。ｐ５３蛋白阳性率也随不典型增生程度增加而增高。ｐ５３表达与大肠腺癌分化程度及Ｄｕｋｅｓ分期有关。大肠腺瘤中ｂｃ１－２和ｐ５３蛋白的表达呈负相关。结果表明，ｂｃ１－２蛋白表达对大肠腺瘤的增殖有一定意义，ｐ５３在大肠腺瘤癌变和大肠腺癌进展中起重要作用。     

膀胱移行细胞癌P21,P185,p53蛋白表达及ras,p53基因突变的检测

为探讨基因的改变在膀胱移行细胞癌发生过程中的意义，应用免疫组织化学及聚合酶链反应－限制性片段长度多肽性法，检测１５０例膀胱移行细胞癌Ｐ２１、Ｐ１８５、ｐ５３蛋白表达以及５０例ｒａｓ、ｐ５３基因突变。结果表明：膀胱移行细胞癌Ｐ２１、Ｐ１８５、ｐ５３蛋白表达阳性率分别为５９．３％（８９例）、５５．３％（８３例）、２９．３％（４４例）。Ｐ２１、ｐ１８５蛋白表达阳性率与膀胱移行细胞癌分级呈负相关（Ｐ＜０．０５），ｐ５３蛋白表达与膀胱移行细胞癌分级呈正相关（Ｐ＜０．０１）。Ｐ２１、ｐ５３蛋白表达阳性率与预后呈显著相关，Ｐ２１与预后呈负相关。７３例膀胱移行细胞癌存在两种以上蛋白共同表达。膀胱移行细胞癌Ｈａ－ｒａｓ癌基因第１２位密码子突变１６例（３２％），ｐ５３基因突变９例（１８％），均为２４８位点突变。Ｈａ－ｒａｓ第１２位点突变随病理分级增高而增高，与膀胱移行细胞癌分级显著相关（Ｐ＜０．０５）。ｒａｓ基因、ｐ５３基因突变与预后显著相关（Ｐ＜０．０５）。ｒａｓ基因、ｐ５３基因突变患者死亡率高于无突变患者。４例膀胱移行细胞癌存在ｒａｓ基因及ｐ５３基因共同突变。     

大肠肿瘤p53基因表达及其临床病理意义

应用免疫组织化学Ｓ－Ｐ法检测了１０６例良，恶性大肠组织中抑癌基因ｐ５３基因表达民政部结果发现；正常大肠粘膜及非肿瘤性息肉均阴性；腺癌中１８．１８％ｐ５３阳性，但均为弱阳性，局灶型，而腺癌组织中４２．１１ｐ５３阳性，其中７５％为强阳性或阳性；癌组织中ｐ５３阳性表达与大肠癌的分化、组织学类型、侵范围是淋巴结转移等因素有关，低分化腺癌及粘液癌阳性率较高，ｐ５３阳性及强阳性者更易于侵出肌层及发生淋巴结转移     

大肠癌和腺瘤中的细胞凋亡及其调控基因表达

目的通过观察结、直肠腺癌和腺瘤中的细胞凋亡及其调控基因ｐ５３、ｂｃｌ－２的表达状态，探讨细胞凋亡及其调控基因在大肠上皮恶性转化进程的不同阶段中的作用。方法利用ＤＮＡ缺口末端标记技术和ｐ５３、ｂｃｌ－２蛋白免疫组化染色，原位观察３２例大肠绒毛状腺瘤和３３例大肠乳头状腺癌中的凋亡细胞和ｐ５３、ｂｃｌ－２蛋白阳性表达细胞的密度与分布，以１５例非肿瘤大肠粘膜做为对照。结果腺瘤和腺癌中的凋亡细胞密度均显著高于非肿瘤粘膜（Ｐ＜０．０１）；腺瘤高于腺癌（Ｐ＜０．０１）。ｐ５３和ｂｃｌ－２蛋白的表达率和表达强度，腺癌和腺瘤高于非肿瘤粘膜（Ｐ＜０．０１），腺癌的表达强度也高于腺瘤（Ｐ＜０．０５）。腺瘤中ｂｃｌ－２蛋白表达阳性组的凋亡细胞密度显著低于ｂｃｌ－２阴性组（Ｐ＜０．０１）。结论细胞凋亡调控异常在大肠癌发病中可能起重要作用。ｂｃｌ－２蛋白在腺瘤和腺癌中均可抑制细胞凋亡，而突变型ｐ５３蛋白可能仅在腺癌中起抑制细胞凋亡的作用。     

p53蛋白表达与上颌窦鳞状细胞癌发生的关系

用免疫组化技术对８例上颌窦正常粘膜、１６例乳头状瘤及癌变、５０例鳞状细胞癌及１４例癌旁粘膜（包括癌旁正常粘膜、单纯增生及不典型增生）ｐ５３蛋白的表达进行了检测。结果显示，上颌窦癌ｐ５３阳性率为６２％（３１／５０）。ｐ５３表达与患者性别、年龄及肿瘤分化程度无关。上颌窦正常粘膜、单纯增生及乳头状瘤ｐ５３表达阴性。不典型增生ｐ５３表达为４／６，其表达与相应鳞癌存在一致性，不典型增生ｐ５３阳性者，相应癌组织亦为阳性，反之亦然。４例乳头状瘤癌变中，３例ｐ５３阳性。研究结果表明，ｐ５３表达是人上颌窦癌发生的早期事件，而与其恶性程度无关，ｐ５３表达发生于不典型增生或乳头状瘤癌变阶段，显示ｐ５３基因突变与上颌窦癌的发生密切相关。研究结果还表明，检测ｐ５３蛋白有助于上颌窦良，恶性病变的鉴别及早期发现上颌窦癌。     

胃癌组织P~（53）蛋白产物的表达与病人预后的关系

采用免疫组化方法对Ｐ￣（５３）蛋白的表达进行观察。结果表明：胃癌组织Ｐ￣（５３）蛋白染色阳性率为３６．５％，肿瘤大于５ｃｍ组、有淋巴结转移和浆膜侵犯及Ⅲ、Ⅳ期胃癌组织Ｐ￣（５３）蛋白染色阳性率分别显著高干肿瘤小于５ｃｍ、无淋巴结转移和浆膜侵犯及Ⅰ、Ⅱ期胃癌组（Ｐ＜０．０１）。Ｐ￣（５３）染色阳性者５年存活率为２１．１％，染色阴性者为５０．０％，两组５年存活率差非常显著（Ｐ＜０．０１）。以上结果提示检测胃癌组织Ｐ￣（５３）蛋白有助于判断胃癌患者预后。     

大肠肿瘤中p53和bcl-2蛋白的表达

目的：研究Ｐ５３和ｂｃｌ－２在大肠肿瘤发生中的作用。方法：应用免疫组化Ｓ－Ｐ法分别检测大肠正常、腺瘤及腺癌中Ｐ５３和ｂｃｌ－２表达。结果：大肠腺癌Ｐ５３表达率高于腺瘤组;Ｐ５３表达与大肠癌的临床病理因素无关,ｂｃｌ－２在正常粘膜基底部上皮细胞表达,在腺瘤（７７．５％）和腺（５５％）ｂｃｌ－２表达差异显著,高分化腺癌ｂｃｌ－２表达率（７３．７％）高于差分化癌（４１．２％）,在腺瘤和腺癌中ｂｃｌ－２和     

宫颈癌组织中HPV16,18E6蛋白表达的观察

目的观察ＨＰＶ１６、１８早期蛋白Ｅ６在人宫颈鳞状细胞癌中的表达并评价Ｅ６单抗的应用价值。方法采用ＳＰ免疫组化染色法,检测４０例宫颈鳞状细胞癌,３０例慢性宫颈炎及３０例正常宫颈组织中ＨＰＶ１６、１８Ｅ６蛋白的表达。结果癌组中Ｅ６的阳性率为６７．５％（２７／４０）,慢性宫颈炎中为３．３％（１／３０）,正常宫颈组织中均为阴性,良、恶组ＨＰＶ１６、１８Ｅ６的阳性率差异有显著意义（Ｐ＜０．０１）。结论ＨＰＶ１６、１８感染与本地区宫颈癌病因学密切相关,Ｅ６单抗可作为预测ＨＰＶ１６、１８感染及宫颈癌早期诊断的标记之一。     

肺癌中MTS1/p16和p53基因产物的表达与细胞增殖的关系

目的：研究肺癌中ＭＴＳ１／ｐ１６和ｐ５３基因产物的表达与细胞增殖的关系。方法：应用Ｓ－Ｐ免疫组织化学方法研究６２例肺癌组织中ｐ１６蛋白和ｐ５３蛋白的表达情况，并进行增殖细胞核抗原（ＰＣＮＡ）检测，计算细胞增殖指数（ｐｒｏｌｉｆｅｒａｔｉｏｎｉｎｄｅｘ，ＰＩ）。结果：６２例肺癌组织中ｐ１６蛋白和ｐ５３蛋白阳性率分别为５８．１％和５９．７％。腺癌ｐ１６蛋白的阳性率明显高于小细胞癌（Ｐ＜０．０５）；淋巴结转移阳性组ｐ１６蛋白的表达显著低于阴性组（Ｐ＜０．０５）；ＰＩ分级为Ⅱ级的ｐ１６蛋白表达显著高于Ⅳ级（Ｐ＜０．０５）。不同组织类型肺癌中ｐ５３蛋白的表达未见明显差异，淋巴结转移阳性组ｐ５３蛋白的表达高于阴性组（Ｐ＜０．０１）；不同ＰＩ分级中ｐ５３蛋白的表达，Ⅳ级明显高于Ⅰ级（Ｐ＜０．０５）和Ⅱ级（Ｐ＜０．０５），Ⅲ级明显高于Ⅰ级（Ｐ＜０．０５）和Ⅱ级（Ｐ＜０．０１）。ｐ１６蛋白低表达和ｐ５３蛋白过表达之间未见明显相关。结论：ｐ１６蛋白低表达和ｐ５３蛋白过表达均有促进肺癌细胞增殖的作用，ｐ１６蛋白的表达与肺癌的细胞分化有关，ｐ５３蛋白过表达对肺癌细胞的转移起重要作用。抑癌基因ｐ５３对ＭＴＳ１／ｐ１６基因无明显调控作     

p53 expression in colorectal adenomas.

To assess the expression of p53 in premalignant lesions, we examined by immunohistochemistry benign colorectal adenomas (n = 72, measuring more than 6 mm and less than 95 mm in diameter) from patients without (group I, n = 23) or with (group II, n = 49) concurrent sporadic colorectal carcinomas. Using a panel of three monoclonal antibodies (PAb 240, PAb 421, PAb 1801) and two polyclonal antibodies (CM1, C19) immunohistological staining was demonstrated in 26% of the cases (19 of 72 adenomas, 7 of 23 from group I and 12 of 49 from group II). In the majority of the cases, p53 positive foci in the adenomas occurred in the most dysplastic areas, although focal positivity was detected in glands that were histologically normal. Expression of p53 protein was also detected in 21 of 30 (70%) colorectal carcinomas of group II. In two cases focal positive staining was observed in the polyps but not in the concurrent carcinomas. Non-neoplastic colonic mucosa and stromal lymphoid cells were negative in all cases examined. Over-expression of p53 in neoplastic tissues detected by immunocytochemistry is generally believed to correlate with the presence of mutation in the gene. This may not be an absolute rule, because in some hemopoietic malignancies, there is evidence that p53 protein may be detectable in the absence of an underlying mutation. These findings therefore represent the highest incidence in colorectal adenomas of abnormalities in the p53 protein expression, probably largely due to underlying mutations. This study also suggests that immunocytochemical demonstration of p53 protein may be a suitable method for the routine detection of subpopulations of cells which, by clonal expansion, could acquire a growth advantage within an adenoma during the neoplastic process.     

Overexpression of p53 protein correlates with a high risk of malignant transformation of adenomas in patients with multiple colorectal adenomas

To assess the correlation of p53 oncoprotein expression with the high risk of developing carcinomas in patients with multiple colorectal adenomas, 25 cases with histologic carcinoma in adenoma (CIA) were examined by immunohistochemistry using a monoclonal antibody specific to human p53 protein (wild and mutant). The 25 cases were classlfied into multiple and single groups. The former contained 13 cases with synchronous multiple colorectal adenomas (one to six adenomas) and adenocarcinoma. The latter included 12 cases with single CIA only. This study revealed an overall incidence of 57.14% of p53 overexpression in carcinomatous lesions and 31.9% in adenomatous lesions, which was statistically significant ( P <0.05). The carcinomatous lesions showed a diffuse staining pattern, whereas the adenomatous lesions showed a focal pattern. A significant finding was that the incidence of p53 overexpression was slgnificantly higher in multiple groups (81.25%) than in single groups (31.43%) in the carcinomatous ( P <0.01) rather than in the adenomatous ( P >0.05) lesions. There were no correlations between p53 overexpression and proliferation activity or carcinoembryonic antigen expression. The results indicate that p53 abnormality may be an important genetic factor responsible for the high risk of developing carcinomas in patients with multiple adenomas.     

An immunohistochemical study of the expression of p53 protein in colon cancer.

A total of 471 cases of colonic adenocarcinomas and 28 cases of colonic adenomas were examined immunohistochemically to evaluate the expression of p53 protein in the light of their relationship with various prognostic factors. A monoclonal antibody, p53 DO-7, was used in the study. Two hundred and fourteen adenocarcinomas (45.5%) showed positive staining for p53, however only three of the adenomas (10.3%) were positive (P < 0.05). p53 was stained to neoplastic nuclei. Adjacent normal mucosal cells were negative. There were no significant correlations between p53 expression and prognostic parameters such as age, sex, gross configuration, modified Astler-Coller stages, microscopic tumor growth patterns, tumor depth, tumor size and lymph node involvements. However, left sided adenocarcinomas (49.3%) expressed p53 more often than right sided adenocarcinomas (35.6%) (P = 0.01). The positive rates were different according to the histologic differentiation; 45.2% in well differentiated, 51.3% in moderately well differentiated, 23.8% in poorly differentiated, and 26.5% in mucinous carcinomas (P = 0.011). The mean survival periods of the p53 positive and negative groups were 29 months and 32 months, respectively (P = 0.385). However, overall survival for patients with grade one and two positive p53 was better than those of grade three and four positive cases (P = 0.028). In conclusion, the result of this multivariate analysis suggests that immunohistochemically strong p53 protein expression (more than 30% of tumor cells) has value in estimating a prognosis for patients with colorectal adenocarcinomas.     

Expression of mdm2 and p53 in epithelial neoplasms of the colorectum.

AIMS: To evaluate the respective roles of mdm2 (murine double minute 2) and p53 in the development of colorectal carcinoma. METHODS: Formalin fixed, paraffin wax embedded tissues from 72 sporadic adenomas and 55 carcinomas were investigated by means of immunohistochemistry for mdm2 and p53. RESULTS: mdm2 was expressed weakly in 17 of 72 (23.6%) adenomas and in 14 of 55 (25.4%) carcinomas. p53 was expressed in 19 of 72 (26.4%) adenomas and in 23 of 55 (41.8%) carcinomas. Four adenomas and five carcinomas showed positive staining for both proteins. Overexpression of p53 in adenomas was associated with moderate and severe dysplasia but not with tumour size. No associations were found between the expression of mdm2 and either the degree of dysplasia or tumour size. In carcinomas, neither the expression of p53 nor mdm2 correlated with Dukes's stage, metastasis, or differentiation. No associations were found between the expression of p53 and mdm2 in either adenomas or carcinomas. CONCLUSIONS: Although mdm2 has been reported to be an oncogene, it does not appear to play a major role in the development of colorectal carcinoma.     

p53 expression patterns in colorectal adenomas and early carcinomas: A special reference to depressed adenoma and non-polypoid carcinoma

The purpose of the present study was to investigate the role of p53 in tumor progression of colorectal adenomas and early carcinomas, while especially focusing on flat tumors (depressed adenomas and non-polypoid carcinomas). Paraffin sections of 61 pure adenomas (33 polypoid, 28 depressed), 26 carcinomas in polypoid adenoma (CIA) and 63 pure carcinomas (36 polypoid, 27 non-polypoid) were examined for immunostaining using p53 monoclonal antibody (PAb 1801). All of the carcinomas were restricted to the mucosa. The number and distribution of the p53 positive tumor cells was evaluated, and then compared with tumor growth patterns and histologlcal features. The incidence of p53 expression in carcinomas (58% in CIA and 51% in pure carcinomas) was significantly higher than that in polypoid adenoma (27% in CIA and 21% in pure adenomas). However, the same incidence In depressed adenomas (51%) was significantly higher than In polypoid adenomas. No correlation in carcinomas was observed between p53 expression and cllnlco-pathologic data except for age. The distribution of p53 positive cells was different between adenomas and carcinomas. There tended to be fewer p53 positive cells in adenomas, even in depressed ones, than in carcinomas and they also tended to be confined to the superficial areas in adenomas, while they were diffusely distributed in carcinomas. Interestingly, the p53 positive cells were more frequently present in the deep mucosal areas than in the superficial areas of some non-polypoid carcinomas. In conclusion, the following hypotheses are suggested: (i) the increase of p53 expression from adenoma to carcinoma supports the hypothesis of an adenoma-carcinoma sequence in a polypoid tumor; (ii) the unique p53 expression in non-polypoid carcinoma suggests the existence of another type of carcinogenesis; and (iii) depressed adenomas are thus considered to have a high potential risk of carcinoma.     

Relation between stage, grade, proliferation, and expression of p53 and CD44 in adenomas and carcinomas of the colorectum.

AIMS--To investigate the changes in and relations among p53, CD44 and MIB-1 expression in adenocarcinomas of the colorectum and to determine whether these changes are progressive across the adenoma-carcinoma sequence. METHODS--Expression of p53 protein, CD44 adhesion molecule and MIB-1 proliferation antigen was detected using immunohistochemistry in 68 colorectal carcinomas and 32 colorectal adenoma. The staining characteristics were compared with degree of dysplasia in adenomas, and differentiation and Dukes' stage in carcinomas. Results were analysed and assessed using Spearman's rank correlation and independent t tests. RESULTS--p53 staining was present in som adenomas and correlated with the degree of dysplasia. There was significantly more staining in carcinomas than adenomas and significant correlation between staining and Dukes' stage. CD44 staining was maximal in adenomas, diminished in carcinomas and was minimal in metastasising carcinomas. There was inverse correlation between p53 and CD44 expression across the adenoma-carcinoma-metastasising carcinoma sequence. MIB-1 expression was highest in carcinomas but did not correlate with either p53 or CD44 expression. CONCLUSIONS--There are progressive changes in p53, CD44 and MIB-1 expression in adenomas and carcinomas. A combination of these tests may prove useful in assessing which patients with adenomas are at greatest risk of progressing to carcinoma.     

p53 protein expression in colorectal adenomas: an immunohistochemical study using an antigen retrieval system

The immunohistochemical expression of the p53 gene product was examined in 91 colorectal adenomas from patients without (group 1,50 cases) or with (group 2,41 cases) concurrent sporadic colorectal carcinoma, and in 15 additional cases of randomly selected carcinomas from group 2 patients. Immunohistochemical reactions were performed with the DO-7 monoclonal and the CM1 polyclonal antibodies, following microwave irradiation of the tissues in an antigen retrieval solution, and the proportion of the immunoreactive cells was semiquantitatively assessed. p53 protein immunoreactivity was present in 46.1% (42, of 91, i.e., 20 out of 50 of group 1 and 22 out of 41 of group 2) and 33% (30 of 91, i.e. 14 out of 50 of group 1 and 16 out of 41 of group 2) of the adenomas using DO-7 and CM1 antibody, respectively. High p53 expression (i.e. immunolabelling of more than 30% of the tumour cell nuclei) was found in 13.2% of the adenomas (12 of 91, i.e. three out of 50 of group 1 and nine out of 41 of group 2; P= 0.025 using the X² test) using the DO-7 antibody, and in 6.6% of the cases (six of 91, i.e. two out of 50 of group 1 and four out of 41 of group 2) using the CM1 antibody. In carcinomas, 80% of the cases (i.e. 12 of 15) were found to express p53 protein with both antibodies. p53 immunoreactivity in colorectal adenomas increased with the degree of dysplasia: only five (17.8%) of the 28 adenomas with mild dysplasia were found to be DO-7 positive, while all of them remained CM1 negative. From the 50 adenomas exhibiting moderate dysplasia, 28 (56%) were DO-7 positive, and 22 (44%) were CM1 positive. Finally, from the 13 adenomas with severe dysplasia, nine (69.2%) and eight (61.5%) were found to be positive with the DO-7 and the CM1 antibody, respectively. Our results indicate that an increased number of group 2 adenomas express p53 protein, when compared with group 1 adenomas, and suggest that a strong correlation exists between p53 protein expression and the degree of dysplasia in colorectal neoplasms.     

p53、ras、c－erbB－2癌基因产物在大肠癌和大肠息肉中的表达

用ｐ５３、ｐ２１、ｐ１８５，通过免疫金银染色方法，对７８例大肠癌、１４例大肠息肉进行了检测。结果显示：大肠癌ｐ５３、ｐ２１、ｐ１８５的阳性率分别为５３．９％、４６．２％、５１．３％；大肠息肉仅有１４．３％｛２／１４）显示ｐ１８５弱阳性。二者之间有显著性差异。大肠癌旁正常粘膜上皮阳性卒ｐ５３为０、ｐ２１２．６％、ｐ１８５５．１％，与其肿瘤区比较Ｐ＜０．０１；７８例大肠癌中，有３３例（４２．３％）ｐ５３与ｐ２１同为阳性，ｐ５３在大肠低分化及粘液腺癌中的阳性表达明显高于高、中分化腺癌（ｐ＜０．０１）。     

Clinical importance of p53 protein in gall bladder carcinoma and its precursor lesions.

AIMS--To study the expression and importance (if any) of p53 protein in gall bladder carcinoma and its precursor lesions. METHODS--Immunohistochemical staining was performed on formalin fixed, paraffin wax embedded histological sections with an anti-human p53 monoclonal antibody (DO-7; Dako Corporation M7001) (24 carcinomas, one adenocarcinoma in situ, six dysplasias, three adenomas and four cases of chronic cholecystitis). Invasive, in situ, and dysplastic areas as well as normal-looking epithelium were sought. Nuclear staining was assessed according to intensity and extent of positive cells. Both variables were graded on a scale of 1-3 and aggregate p53 scores were obtained (range: 0, 2-6). Only p53 scores of > or = 3 were regarded as significant. RESULTS--Clinically important amounts of p53 were expressed in 92% of invasive carcinomas, 86% of carcinoma in situ, and 28% of dysplastic areas. None of the adenomas contained clinically important amounts of p53. Normal epithelium, present in all the cases, did not express p53 except in one case of moderately differentiated adenocarcinoma (p53 score 3). In general, there was no difference in the prevalence of p53 protein expression between dysplasias associated with, and those unassociated with invasive disease. There was a tendency for higher grade carcinomas to express more p53 protein. CONCLUSIONS--The distribution of p53 protein in invasive carcinomas and the adjacent dysplastic and preinvasive lesions suggests that it is more commonly expressed than previously thought. The fact that p53 protein is also expressed in cases of dysplasia and carcinoma in situ unassociated with invasive malignancy lends further support to the contention that p53 gene mutations may have a role in the pathogenesis of gall bladder cancer. Expression of p53 protein may possibly be an indication of likely disease progression from dysplasia, to carcinoma in situ, to invasive disease.