Immunohistochemical analysis of c-erbB-2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas

Expression of the product of the c-erbB-2 gene, a proto-oncogene related to, but distinct from c-erbB-1 encoding the epidermal growth factor receptor (EGF-R), was investigated in human urinary bladder carcinomas. In addition, levels of EGF-R and transferrin receptor were also analyzed using an immunohistochemical approach, and the results compared with histological pattern and grading, and tumor staging. Increased expression of c-erb B-2 product was found in 32% of cases (7/22), a positive reaction being observed in 60% of transitional cell carcinoma (TCC) Grade 3 lesions (3/5), 20% of Grade 2 TCCs (2/10) and 100% of adenocarcinomas (AC) (2/2), but in none of the cases of squamous cell carcinoma (SCC). Although no statistical correlation with staging was evident, TCCs or SCCs of high grade and stage often showed EGF-R-positive staining, whereas other well differentiated lesions and normal bladder epithelium were generally negative. Most cases of urinary bladder carcinoma were positive for the transferrin receptor, which was not detected in normal bladder. The results thus suggested that a positive reaction for c-erbB-2 product is correlated with TCC histological grading or AC morphology. A high intensity of EGF-R staining in human bladder carcinomas may be associated with poor differentiation and invasion, whereas transferrin receptor expression might reflect tumor growth.     

c-myc, c-erbB-1 and c-erbB-2 expressions in urothelial carcinoma

The expression of c -myc , c- erb B-1 and c- erb B-2 In 24 cases of urothelial carcinoma by Southern and northern blot analysis, and immunohistochemistry was examined. The results were compared with the pathological grade and stage. We found elevated mRNA expressions of c- myc and c- erb B-1 In 19 and 11 of 21 cases, respectively, but there was no apparent amplification or rearrangement of these oncogenes in any of the cases examined. By immunohistochemistry using anti-epidermal growth factor receptor antibody, most of the cases showed positbe immunoreactivity on the cancer cell membranes, and cancers of higher pathological grade and stage showed more intense staining. By contrast, amplification of c- erb B-2 was detected in four of 24 cases, all of which were assigned to a high pathological grade (G3). Elevated c- erb B-2 mRNA levels appeared to correlate with the pathological grade of the cancers. Positive immunohistochemical reactions to c- erb B-2 were found in the cancer cell membranes in three of 24 cases, which were accompanied by amplification and eievated mRNA levels of c -erb B -2 . In conclusion, expressions of c- myc , c- erb B-1 and c- erb B-2 were all elevated in the majority of urothellal carcinomas, but the amplification was not universal.     

Cytoplasmic c-erbB-2 protein expression correlates with survival in Dukes' B colorectal carcinoma

The prognostic significance of c- erb B-2 expression was studied in paraffin wax embedded colorectal cancer tissue using a monoclonal antibody. One hundred and sixty-four patients with Dukes' B disease were studied. Membranous staining was not detected in any case. Cytoplasmic c- erb B-2 staining was seen in 55 cancers (33.5%). Cytoplasmic taining was unrelated to patient age ( P = 0.31), sex ( P = 0.69), tumour site ( P = 0.69), size ( P = 0.57), histological grade ( P = 0.42) or ploidy status ( P = 0.21) but was found more frequently in obstructing cancers ( P = 0.03). Mean follow up of the patient population was 6.3 years. Five-year-survival estimated by the Kaplan-Meier life-table method was 47% for those with cytoplasmic c- erb B-2 staining and 77% for those without (log rank analysis; P ⋜ 0.0001). Stepwise regression analysis identified c- erb B-2 staining (relative risk, 2.51; P = 0.0005) and bowel obstruction (relative risk, 1.99; P = 0.015) as independent predictors of survival. It is suggested that cytoplasmic c- erb B-2 expression may provide a useful marker of tumour behaviour in Dukes' B colorectal cancer.     

c-erbB-3 protein expression in human breast cancer: comparison with other tumour variables and survival

c- erb B-3 protein expression was investigated immunohistochemically in a series of 97 malignant breast tumours using the monoclonal antibody RTJ1. Twenty-eight cases (28.8%) showed c- erb B-3 overexpression, 31 cases (32%) showed normal levels of c- erb B-3 and 38 cases (39.2%) were c- erb B-3 negative. c- erb B-3 overexpression was positively but not significantly related to negative lymph node status and survival over a 10-year follow-up period.     

Neural variant of fetal rhabdomyoma and naevoid basal cell carcinoma syndrome

A series of 19 cases of carcinoma ex-pleomorphic adenoma was studied for the immuno-expression of c- erb B-2 oncoprotein. Twelve tumours showed a malignant component with only one histological type; in the remaining seven there was co-existence of areas of various carcinoma types, adenocarcinoma NOS being the most frequent. Membranous c- erb B-2 reactivity was found in 21.1% of the cases, all corresponding to high-grade adenocarcinomatous areas. The low-grade carcinoma types that formed the malignant mixed tumours components were negative. Benign pleomorphic adenoma areas, either adjacent or intermingled with carcinomatous areas, were also consistently negative, proving that c- erb B-2 accumulation is associated with the acquisition of the malignant phenotype. The finding of a preferential association between c- erb B-2 overexpression and high-grade malignant mixed tumour may indicate prognostic implications for the oncogene protein and may also be indicative of its specific relationship with the putative pathway of malignant transformation in pleomorphic adenomas.     

Transitional cell carcinomas of the ovary and bladder are immunophenotypically different

AIMS: Transitional cell carcinoma (TCC) of the ovary is a subtype of ovarian cancer whose main characteristic is its histological resemblance to TCC of the bladder. Thrombomodulin (TM), a surface glycoprotein commonly expressed in normal and neoplastic urothelium, has been proven to be a good marker for TCC of the bladder. To better define the phenotype of TCC of the ovary, we investigated TM, cytokeratin 20 and carcinoembryonic antigen (CEA) expression in 15 TCCs of the ovary and compared their phenotype with that of 20 TCCs of the bladder, and 20 serous and 10 endometrioid carcinomas of the ovary. METHODS AND RESULTS: Immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections using the avidin-biotin-peroxidase complex method. All 20 TCCs of the bladder stained for TM and cytokeratin 20, and 13 stained for CEA. None of the TCCs of the ovary reacted for TM or cytokeratin 20, and only two expressed CEA. All of the serous and endometrioid carcinomas were negative for TM and cytokeratin 20. CEA positivity was observed in two of the serous carcinomas, but in none of the endometrioid carcinomas. CONCLUSION: The immunophenotype of TCC of the ovary is similar to that of other surface carcinomas of the ovary, but differs from that of TCC of the bladder. Since immunohistochemical procedures are often used in the diagnosis and classification of both primary and metastatic tumours, it is important to be aware of these differences in immunophenotype.     

Expression and prognostic value of c-erbB-2 oncogene product in human phaeochromocytomas

Aims : Amplification of c- erb B-2 proto-oncogene has been reported in endocrine tumours, but the results were unclear and no predictive prognostic value has been established in the case of phaeochromocytoma. We investigated the immunohistochemical expression of c- erb B-2 oncogene in 34 cases of human phaeochromocytoma (27 sporadic, seven familial type MEN (multiple endocrine neoplasm)) in order to find out if it could be used to differentiate sporadic and familial forms and whether c- erb B-2 expression is related to tumour biological behaviour. Methods and results : All the cases showed diffuse, generally heterogeneous, intracytoplasmic granular c- erb B-2 staining. The percentage of tumour cells expressing c- erb B-2 was used as the comparative variable. The percentage of c- erb B-2 positive cells had a statistically significant ( P  < 0.001) relationship with tumour aggressiveness, as manifested by the presence of distant metastasis or association with other malignant neoplasms. We also found significantly higher levels ( P  = 0.007) of c- erb B-2 overexpression in MEN phaeochromocytoma than in sporadic cases. Conclusions : These results clarify the important role of c- erb B-2 proto-oncogene in the pathogenesis of human phaeochromocytoma and confirm the unfavourable prognostic significance of c- erb B-2 expression.     

膀胱移行细胞癌中fhit基因和survivin基因的表达和意义

目的探讨fhit基因和survivin基因在膀胱移行细胞癌中的表达和意义。方法用免疫组化S-P法检测62例膀胱移行细胞癌组织及10例正常膀胱粘膜组织中fhit蛋白和survivin蛋白的表达。结果10例正常膀胱粘膜组织中fhit蛋白表达均为阳性，survivin蛋白表达均为阴性；fhit蛋白在膀胱移行细胞癌中阳性表达率为46．77％（29／62），肿瘤不同分级中随恶性程度的增长表达减少，Ⅰ级与Ⅲ级比较，差异有统计学意义（P〈0．05），不同临床分期中随分期的增长表达减少，Tis～T1与T2～T4比较，差异无统计学意义（P〉0．05）；survivin蛋白在膀胱移行细胞癌中阳性表达率为56．5％（35／62），肿瘤不同分级中随恶性程度的增高表达增高（P〈0．05），不同临床分期中随分期的增长表达增高，差异有统计学意义（P〈0．05）；fhit蛋白和survivin蛋白表达相关（P〈0．05）。结论Fhit基因和survivin基因在膀胱移行细胞癌的发生、发展过程中起着重要的作用。Fhit基因可能通过肿瘤凋亡抑制途径发挥作用的。     

Brenner Tumor of the Ovary: A Comparative Immunohistochemical and Ultrastructural Study With Transitional Cell Carcinoma of the Bladder

Because of a fancied light microscopic resemblance to transitional epithelium (urothelium), Brenner tumor (BT) of the ovary is commonly described as a transitional cell neoplasm. An inability to detect a great deal of similarity between the two at the ultrastructural level prompted this electron microscopic study comparing 3 benign Brenner tumors with normal urothelium and 6 transitional cell carcinomas (TCC) of varying histologic grade from the urinary bladder. To complement the ultrastructural observations, the immunophenotype of 8 benign BTs was evaluated together with that of 12 TCCs of the bladder using antibodies to thrombomodulin (TM), cytokeratin 20, cytokeratin 7, and carcinoembryonic antigen (CEA), all of which havebeen shown to react with TCCs of urothelial origin. At the ultrastructural level, there was only limited evidence of a morphologic likeness between the epithelial cells of BTs and those of the benign or neoplastic urothelium. The immunophenotype of the two tumors also differed significantly in that there was no reactivity for TM or cytokeratin 20 in the BTs, while these markers were expressed in the TCCs. Both BTs and TCCs were positive for cytokeratin 7 and may express CEA.     

Expression of cyclooxygenase-2 in human transitional cell carcinoma of the urinary bladder

Recent studies suggest that expression of cyclooxygenase-2 (Cox-2) is elevated in transitional cell carcinoma (TCC) of the urinary bladder and that inhibition of Cox-2 activity suppresses bladder cancer in experimental animal models. We have investigated the expression of Cox-2 protein in human TCCs (n = 85), in in situ carcinomas (Tis) of the urinary bladder (n = 17), and in nonneoplastic urinary bladder samples (n = 16) using immunohistochemistry. Cox-2 immunoreactivity was detected in 66% (67 of 102) of the carcinomas, whereas only 25% (4 of 16) of the nonneoplastic samples were positive (P: < 0.005). Cox-2 immunoreactivity localized to neoplastic cells in the carcinoma samples. The rate of positivity was the same in invasive (T1-3; 70%, n = 40) and in noninvasive (Tis and Ta; 65%, n = 62) carcinomas, but noninvasive tumors had a higher frequency (32%) of homogenous pattern of staining (>90% of the tumor cells positive) than the invasive carcinomas (10%) (P: < 0.05). However, several invasive TCCs exhibited the strongest intensity of Cox-2 staining in the invading cells, whereas other parts of the tumor were virtually negative. Finally, strong Cox-2 positivity was also found in nonneoplastic ulcerations (2 of 2) and in inflammatory pseudotumors (2 of 2), in which the immunoreactivity localized to the nonepithelial cells. Taken together, our data suggest that Cox-2 is highly expressed in noninvasive bladder carcinomas, whereas the highest expression of invasive tumors associated with the invading cells, and that Cox-2 may also have a pathophysiological role in nonneoplastic conditions of the urinary bladder, such as ulcerations and inflammatory pseudotumors.     

Immunohistochemical studies on oncogene products (EGF-R,c-erbB-2) and growth factors (EGF,TGF-α) in human breast cancer: their relationship to oestrogen receptor status,histological grade,mitotic index and nodal status

Summary In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF- and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-; positive EGF-R and TGF-; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF- correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF- are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immuno-histochemical demonstration of expression of EGF-R and TGF- may provide useful information for selecting the appropriate treatment.     

Expression of MUC5AC apomucin in transitional cell carcinomas of the urinary bladder and its possible role in the development of mucus-secreting adenocarcinomas

The histogenesis of primary nonurachal mucus-producing adenocarcinomas of the urinary bladder including signet ring cell carcinomas remains to be elucidated, since the normal bladder contains neither columnar nor mucus-secreting glandular epithelium. Based upon the assumption that adenocarcinomas may develop secondarily from pre-existent transitional cell carcinomas (TCC) by a metaplastic process, it was the purpose of the current immunohistochemical study to analyze whether urothelial carcinomas are capable of secreting MUC5AC apomucin, using the monoclonal antibody 45MI. This antibody has been initially demonstrated to strongly react with the mucus-producing columnar cells of the surface gastric epithelium, recognizing a specific epitope located on the peptide core of glycoproteins as major components of mucins. Nine of 64 uniformly differentiated papillary (14.1%) and 5 of 66 nonpapillary (solid) TCC with a uniform urothelial differentiation (7.6%) expressed the MUC5AC antigen, yielding an overall incidence of 10.8%. Transitional cell carcinomas with a focally altered cellular and structural differentiation (squamous cell, pseudoglandular, true glandular and mixed differentiation) stained positively in a substantially higher percentage of 43.8% (21 of 48 cases). A positive immunoreactivity was also observed in 3 of 19 mixed transitional cell and nonurothelial carcinomas. The tumor-associated resurgence of normally cryptic MUC5AC antigenic determinants in transitional cell carcinomas is considered as a re-expression of oncofetal antigenicity, probably as a result of the embryologic origin of the urinary bladder from the pluripotent tissues of the cloacal endoderm and the mesodermal wolffian ducts. Our findings may help to better understand the histogenetic development of mucus-secreting vesical adenocarcinomas from pre-existent urothelial carcinomas.     

Value of thrombomodulin immunostaining in the diagnosis of transitional cell carcinoma: a comparative study with carcinoembryonic antigen

Aims: Thrombomodulin (TM) is a surface glycoprotein involved in the regulation of intravascular coagulation that has been reported to be expressed in a variety of tumours. We investigated TM expression in transitional cell carcinoma (TCC) and compared the value of TM immunostaining with that of carcinoembryonic antigen (CEA) for differentiating TCC from other tumours with which it may be confused.  

Methods and results:

Immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections using the avidin–biotin–peroxidase complex method. TM immunoreactivity was observed in 80 of 91 primary (51/58 urinary bladder, 10/12 renal pelvis, 3/3 ureter, 15/15 prostate, 1/3 ovary), and 18 of 20 metastatic TCCs expressed this marker. Only 37 of the 91 primary (23/58 urinary bladder, 4/12 renal pelvis, 1/3 ureter, 9/15 prostate, 0/3 ovary) and six of the 20 metastatic TCCs reacted for CEA. In order to evaluate the practical utility of TM immunostaining in surgical pathology, 30 adenocarcinomas of the prostate, 18 of the bladder, 12 of the colon, and 22 renal cell carcinomas were also stained for these markers. CEA reactivity was obtained in 12 of 30 adenocarcinomas of the prostate, 12 of 18 of the bladder, and 12 of 12 of the colon, but in none of the 22 renal cell carcinomas. Only three of the 18 adenocarcinomas of the bladder showed focal TM reactivity, but no staining for this marker was observed in any of the other types of tumours.  

Conclusions:

TM is a more sensitive marker than CEA for TCC and, because it has a more restricted reactivity with other tumours, TM has more practical value in separating TCCs from adenocarcinomas of the prostate, colon and bladder, and renal cell carcinomas than CEA.     

Human urinary bladder transitional cell carcinomas acquire the functional Fas ligand during tumor progression

The interaction between FasL on tumor cells and Fas on lymphocytes may represent a tumor immune escape mechanism. We explored FasL expression and function in human urinary bladder transitional cell carcinomas (TCCs). FasL expression was observed in situ in 45% of TCCs (n = 45) and was absent in normal urothelium (n = 20). A correlation existed between FasL expression and high tumor grade (0% in G1, 14% in G2, and 75% in G3; P < 0.0001) and stage (13% in superficial Ta-T1 versus 81% in invasive T2-T4; P < 0.0001). FasL function was shown by the ability of two FasL-positive primary culture TCC cell lines (established from two FasL-positive invasive TCCs) to induce Fas-mediated killing not only of conventional Fas-sensitive targets (such as Jurkat cells or phytohemagglutinin-lymphoblasts), but also of autologous T lymphocytes generated in a mixed lymphocyte tumor-cell culture. In addition, an association between FasL expression by TCC cells and activated caspase-8, -9, and -3 expression by interferon-gamma-producing CD8-positive tumor-infiltrating lymphocytes was observed in situ. Our results show a functional expression of TCC-expressed FasL that correlates with tumor progression. These results suggest that TCC-expressed FasL may induce apoptosis of anti-tumor T lymphocytes in vivo, providing new insights on the mechanisms involved in bladder TCC progression.     

OVEREXPRESSION OF DIFFERENT MEMBERS OF THE TYPE 1 GROWTH FACTOR RECEPTOR FAMILY AND THEIR ASSOCIATION WITH CELL PROLIFERATION IN PERIAMPULLARY CARCINOMA

The expression of epidermal growth factor receptor (EGFR), c- erb B-2, and c- erb B-3 was examined immunohistochemically in 57 cases of periampullary carcinoma. The percentage of Ki-67-positive cells was also examined in the same tissue, to determine the relationship between the expression of the members of the type 1 growth factor receptor family and cell proliferation. In carcinoma of the head of pancreas, the percentage of cases with overexpression of c- erb B-3 was significantly higher than with overexpression of c- erb B-2 and EGFR. In contrast, in lower bile duct carcinoma and carcinoma of the ampulla of Vater, the percentages of cases with overexpression of c- erb B-2 was greater than with overexpression of other growth factor receptors. A higher percentage of cases with overexpression of c- erb B-3 in pancreatic head carcinoma and overexpression of c- erb B-2 in carcinoma of the ampulla of Vater was found in Ki-67 antigen-positive cases. Moreover, the overexpression of c- erb -3 in pancreatic head carcinoma, c- erb -2 in ampulla of Vater carcinoma, and Ki-67 in both carcinomas was found to be associated with poor patient outcome. These results demonstrate that different members of the type 1 growth factor receptor family are overexpressed in different carcinomas of the periampullary region.     

Transitional cell carcinomas and nonurothelial carcinomas of the urinary bladder differ in the promoter methylation status of the caveolin-1, hDAB2IP and p53 genes, but not in the global methylation of Alu elements

Tumor suppressor genes play a prominent role in the modification and progression of urinary bladder carcinogenesis as a result of classic genetic alterations. Little is known about the potential significance of epigenetic events, mediated by DNA hypermethylation. This prompted our investigation to explore the global Alu methylation and the promoter methylation of the novel putative tumor suppressor genes caveolin-1 and hDAB2IP, and of p53 in transitional cell carcinomas (TCC), squamous cell carcinomas and undifferentiated small cell carcinomas of the urinary bladder. Quantitative GeneScan analysis revealed that the various histopathological tumor entities showed considerable interindividual variations in the global methylation, but the overall rate did not significantly differ between the various cancer subtypes. With methylation-specific PCR, a high frequency of methylation of the promoter region of the caveolin-1 gene was detected in undifferentiated small cell carcinomas (50%) and in squamous cell carcinomas (25.9%), while TCC were found not to be methylated. By immunohistochemistry, all squamous cell carcinomas showed a strong diffuse overexpression of caveolin-1, whereas undifferentiated small cell cancers lacked any expression. High-grade, high-stage TCC disclosed a higher incidence (60%) and a substantially stronger expression than low-grade, low-stage TCC (42.9%). Our findings suggest that hypermethylation of the caveolin-1 gene and an abnormal protein expression play a crucial role in cell differentiation, and in the phenotypical conversion of TCC into nonurothelial carcinomas. Promoter methylation of the hDAB2IP gene occurred more frequently in advanced muscle invasive (72.7%) than in superficial noninvasive (50%) TCC. DNA hypermethylation of p53 was detected in a quarter of the low-grade, low-stage TCC and undifferentiated small cell carcinomas, but only sporadically in squamous cell carcinomas, and was absent in high-grade, high-stage TCC. In conclusion, aberrant methylation and abnormal protein expression of the caveolin-1-gene is involved in the formation of nonurothelial carcinomas of the urinary bladder and promoter methylation of the hDAB2IP gene in the progression of TCC from a low to a high malignant potential.     

Brenner tumor of the ovary: a comparative immunohistochemical and ultrastructural study with transitional cell carcinoma of the bladder

Because of a fancied light microscopic resemblance to transitional epithelium (urothelium), Brenner tumor (BT) of the ovary is commonly described as a transitional cell neoplasm. An inability to detect a great deal of similarity between the two at the ultrastructural level prompted this electron microscopic study comparing 3 benign Brenner tumors with normal urothelium and 6 transitional cell carcinomas (TCC) of varying histologic grade from the urinary bladder. To complement the ultrastructural observations, the immunophenotype of 8 benign BTs was evaluated together with that of 12 TCCs of the bladder using antibodies to thrombomodulin (TM), cytokeratin 20, cytokeratin 7, and carcinoembryonic antigen (CEA), all of which havebeen shown to react with TCCs of urothelial origin. At the ultrastructural level, there was only limited evidence of a morphologic likeness between the epithelial cells of BTs and those of the benign or neoplastic urothelium. The immunophenotype of the two tumors also differed significantly in that there was no reactivity for TM or cytokeratin 20 in the BTs, while these markers were expressed in the TCCs. Both BTs and TCCs were positive for cytokeratin 7 and may express CEA.     

FEZ1/LZTS1 is down-regulated in high-grade bladder cancer, and its restoration suppresses tumorigenicity in transitional cell carcinoma cells

FEZ1/LZTS1 is a tumor suppressor gene that maps to chromosome 8p22, a chromosomal region frequently deleted in many human malignancies, including transitional cell carcinoma (TCC) of the urinary bladder. FEZ1/LZTS1 alterations have been reported in esophageal, breast, prostate, and gastric carcinomas. Fez1 expression was studied in five TCC-derived cancer cell lines by Western blot analysis and in 60 primary TCCs of the urinary bladder by immunohistochemistry. Fez1 protein was absent or reduced in four of five cell lines and in 37 of 60 primary TCC examined. We also restored Fez1 protein expression in human SW780 TCC-derived cells lacking endogenous Fez1 protein to study the effects of Fez1 expression on cell proliferation, cell kinetics, and tumorigenicity in BALB/c nude mice. In vitro transduction of SW780 Fez1-negative cell, with Ad-FEZ1, inhibited cell growth, altered cell cycle progression, and suppressed subcutaneous tumor growth in nude mice. These results suggest that FEZ1/LZTS1 gene plays a role in the development of TCC of the urinary bladder by acting as a bona fide tumor suppressor gene both in vitro and in vivo.     

Immunohistochemical analysis of bcl-2 expression in transitional cell carcinoma of the bladder.

AIMS: To evaluate the expression of bcl-2 in transitional cell carcinoma (TCC) of the bladder; to compare bcl-2 expression with clinicopathological findings, p53 immunoreactivity, proliferating cell nuclear antigen (PCNA) expression, 2c deviation index (2cDI), 5c exceeding rate (5cER), and the mean nuclear area (MNA). METHODS: Cystectomy specimens from 77 patients with untreated, non-metastatic TCC of the bladder were studied. Expression of bcl-2, p53 and PCNA was detected immunohistochemically using the following monoclonal antibodies: bcl-2/124, DO-7 and PC10, respectively. Nuclear DNA content was analysed using static cytometry. RESULTS: Bcl-2 was expressed in 19 (24.7%) of 77 TCCs and in 74 (96.1%) of 77 normal samples of transitional epithelium (taken from normal tissue adjacent to the tumour in each case). In all cases, bcl-2 immunoreactivity was more intense in normal transitional epithelium than in TCC. In normal transitional epitehlium and superficial TCC bcl-2 immunoreactivity was observed at the basal layer, and not at the invasive front. Bcl-2 immunoreactivity was invesely correlated with histological grade and p53 immunoreactivity, and was not correlated with the pT category, disease progression, PCNA expression, 2cDI, 5cER, and the MNA. No significant correlation was found between bcl-2 expression and overall survival. CONCLUSIONS: Bcl-2 expression in TCC of the bladder seems to be associated with a less aggressive phenotype and does not play an important role in tumour progression.     

p53、c-erbB-2、PCNA和EGFR在膀胱癌中过表达及其意义

目的：研究癌基因和抑癌基因蛋白产物在膀胱移行细胞癌中异常表达与病理分级、临床分期、复发和预后的关系。方法：应用免疫组化Ｓ－Ｐ法检查１１７例膀胱移行细胞癌组织中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ的表达水平。结果：１１７例膀胱移行细胞癌中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ阳性表达率分别为４７．０％、２９．９％、５３．８％和４８．７％。ｐ５３和ＰＣＮＡ阳性表达产物定位于肿瘤细胞核内，ｃ－ｅｒｂＢ－２阳性表达产物定位于细胞膜上，ＥＧＦＲ阳性表达产物定位于细胞膜或细胞浆内。结果表明ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ异常表达与膀胱癌的分级、分期、复发及术后生存率等之间有统计学意义。结论：ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ异常表达有助于评估膀胱癌预后，多基因异常表达作为预后评价指标更有意义。