Immunohistochemistry of pS2 in normal human breast and in various histological forms of breast tumours

Expression of pS2 was studied by immunocytochemistry in normal breast tissue ( n = 20), benign tumours ( n = 9) and 145 breast cancers representative of the different histological types. pS2 immunostaining was scored as negative (D1 = 0-5% stained cells), positive (D2 = 5-75% stained cells) or highly positive (D3 > 75% stained cells). pS2 protein was evident in all normal breast samples examined. Six of nine benign lesions showed pS2 staining. In both cases, immunostaining was weaker than in breast cancers. Of breast cancers, 77/145 (53.1%) were pS2 positive, including 33.1% with intense staining. The presence of pS2 was not correlated with the age of patients, the size of the primary tumour, or lymph node status, but was correlated with histological grading and nuclear grading. pS2 expression was also correlated with menopausal status and oestrogen receptor status (59% of receptor-positive tumours were pS2 positive), but not to progesterone receptor status. pS2 expression in breast carcinomas is not a characteristic of specific histological types. Although this protein is predominantly expressed in oestrogen receptor-positive and differentiated tumours, it shows oestrogen-independent expression in about 30% of cases.     

Expression of the apoptosis suppressing bcl-2 protein in transitional cell bladder tumours

The expression of bcl-2 protein was studied by immunohistochemistry using a monoclonal antibody in 158 cases of transitional cell bladder tumours. The bcl-2 protein was expressed in basal cells in normal transitional epithelium and 68% of the transitional cell tumours showed bcl-2 positivity in the basal cells. The expression of bcl-2 in basal cells was positively correlated to over-expression of epidermal growth factor receptor in tumour cells. The expression of bcl-2 in non-basal cells was weak in 20% and strong in an additional 13% of tumours. The expression of bcl-2 in non-basal cells was positively correlated to T-category, M-category, grade, papillary status, DNA ploidy, S phase fraction, mitotic index, nuclear area and over-expression of epidermal growth factor receptor. Recurrence-free interval of Ta-T1 tumours was related to bcl-2 positivity in non-basal cells. Tumours with bcl-2 positive non-basal cells had an unfavourable prognosis but, in multivariate analysis, expression of bcl-2 had no independent prognostic value.     

pS2 protein in gastric carcinoma and normal gastric mucosa: Association with clinicopathological parameters and patient survival

The presence of pS2 protein (pS2) was studied in a total of 120 consecutive patients with gastric carcinomas. This immunohistochemical study found pS2 expression in 48 per cent (n=58) of carcinomas. pS2 expression was also detected in normal gastric mucosa in 95 per cent (n=102) of specimens in upper antral mucopeptic glands and deep foveolar cells of the gastric pits but not in intestinal metaplasia. There was a significant statistical correlation between pS2 expression and extent of tumour growth (pT state) and expression of pepsinogen II by the tumours. There was no statistical correlation with clinical features such as patient age or sex or other pathological parameters (tumour stage, size, grade, and localization or growth pattern according to histological classification). There were no statistically significant differences in survival times between patients with pS2-positive and pS2-negative tumours. In contrast to findings concerning breast cancer, pS2 expression in gastric carcinomas has no influence on the patient's prognosis. On the other hand, strong expression of pS2 by surface epithelium of normal gastric mucosa may indicate that pS2 might play a role in physiological cell renewal of normal gastric mucosa.     

Expression of the pS2 peptide in primary breast carcinomas: Comparison of membrane and cytoplasmic staining patterns

The pS2 protein is oestrogen-regulated in breast cancer cell lines. Previous studies have shown a relationship to oestrogen receptor in primary breast carcinomas. This study examined 178 breast carcinomas for pS2 using immunohistochemistry. A high frequency (77 per cent) of positive tumours was found, using a 10 per cent cut-off point to define a positive tumour. There was no relationship with menopausal status or node status, a significant association with differentiation, a weak association with oestrogen receptor, and no association with progesterone receptor or overall survival. Two patterns of cellular localization were observed: cytoplasmic and membrane. The former showed a stronger relationship with oestrogen receptor status, although there were oestrogen receptornegative tumours with marked pS2 staining. Membrane staining showed a stronger relationship with differentiation, with a staining pattern similar to that observed for milk fat globule membrane. The staining patterns observed may support a role for pS2 in a secretory mechanism. However, the expression and function of pS2 in breast carcinomas emain complex, and are not simply related to oestrogen regulation.     

Role of galectin-3 in the pathogenesis of bladder transitional cell carcinoma

Galectins constitute an evolutionary conserved family that binds to β-galactosides. There is growing evidence that galectins are implicated in essential biological processes such as cellular communication, inflammation, differentiation and apoptosis. Galectin-3 is one of the best-known galectins, which is found in vertebrates. Galectin-3 has been shown to be expressed in some cell lines and plays important roles in several physiological and pathological processes, including cell adhesion, cell activation and chemoattraction, cell cycle, apoptosis, cell growth, and differentiation. Moreover, this galectin is of interest due to its involvement in regulation of cancer. Changes in galectin-3 expression are commonly seen in cancerous and pre-cancerous conditions and galectin-3 may be involved in the regulation of cancer cell activities that contribute to tumourigenesis, cancer progression and metastasis. Finally, galectin-3 seems to be involved in cell events in tumor microenvironment, and therefore it could be considered as a target in transitional cell carcinoma therapies. This review aims to describe recent progress in understanding the role of galectin-3 in cancer biology, with emphasis on bladder tumor progression and metastasis.     

膀胱移行细胞癌中MK表达与其临床病理特征及预后的关系

目的： 研究中期因子（MK）蛋白在膀胱移行细胞癌组织中的表达，探讨其与膀胱癌临床病理特征及术后患者预后的关系。方法: 采用SP免疫组化染色法检测50例手术切除膀胱移行细胞癌组织和10例正常膀胱黏膜中MK表达，分析MK在膀胱癌组织中的表达与其临床对应的各项病理参数的关系，对其中40例有随访资料者的MK表达与预后的关系进行统计学分析。结果: MK在膀胱癌组织中表达率为90％(45/50)，在人正常膀胱组织中无表达或弱表达；在膀胱癌中随肿瘤侵润深度和分级的增加，MK表达逐步增强（P<0.05,P<0.01）。MK表达与性别、年龄、肿瘤大小、数目、初复治无相关（P＞0.05）。生存分析表明，MK低表达组1、3、5年生存率分别为81.8%、81.8%、72.7%，MK高表达组1、3、5年生存率分别为63.6%、36.4%、18.2%，MK高表达组生存率显著低于MK低表达组，组间生存率差异显著（P＜0.05）。结论: MK在膀胱移行细胞癌组织中高表达，在正常膀胱黏膜上皮无或弱表达。MK随肿瘤分期和分级的增加表达逐步增强，而与患者性别、年龄、肿瘤大小、数目、初复治无相关。MK表达与膀胱癌术后患者的预后相关，MK呈高表达者的生存时间比低表达者短。     

膀胱移行细胞癌nm23蛋白表达及临床意义

目的 :探讨膀胱移行细胞癌nm2 3蛋白的表达及其与预后的关系。方法 :应用S P法免疫组化技术 ,检测 5 5例膀胱移行细胞癌nm2 3蛋白的表达。结果 :5 5例膀胱移行细胞癌中 ,nm2 3蛋白表达阳性率 6 3 6 % ,在膀胱移行细胞癌Ⅰ、Ⅱ、Ⅲ级中分别为 87 5 %、6 5 %、42 1%。nm2 3蛋白表达阳性率随病理分级增高而降低 ,Ⅰ级与Ⅲ级、Ⅰ级 +Ⅱ级与Ⅲ级比较差异有显著性 (P <0 0 5 ) ,与肿瘤大小、转移及预后相关 (P <0 0 1,P <0 0 5 )。结论 :nm2 3蛋白检测有助于判断膀胱移行细胞癌恶性程度及预后     

Prostatic involvement by transitional cell carcinoma in patients with bladder cancer and its prognostic significance

To study the importance of prostatic involvement by transitional cell carcinoma (TCC) in patients with bladder cancer, we examined the entire prostates by whole-mount sections from 214 radical cystoprostatectomy specimens for detailed patterns of involvement by TCC and correlated the results with lymph node metastasis and patients' survival. Prostatic involvement by TCC was detected in 69 (32%) of 214 cases. Among them, 30 (43%) patients had carcinoma in situ (CIS) and the other 39 (57%) were invasive TCC. Carcinoma in situ occurred in either prostatic urethra (n = 6, 20%) or, more commonly, in prostatic ducts/acini (n = 14, 47%), and in a combination of prostatic urethra and ducts (n = 10, 33%). Ten (26%) of the invasive TCC resulted from direct penetration from the primary tumor in the bladder, and the remaining 29 (72%) cases arose from prostatic urethra/ducts, of which 11, 13, and 5 invaded the lamina propria, prostatic stroma, and periprostatic or seminal vesical tissue, respectively. Both prostatic TCC involvement and nodal metastasis were highly significant prognostic factors for patients' survival and the survival significance of prostatic TCC involvement still existed regardless of lymph node status. Furthermore, the presence of prostatic CIS and degrees of prostatic invasion are associated with nodal metastasis and survival. Patients with prostatic CIS or urethral lamina propria invasion had a similar, but higher incidence of lymph node metastasis and lower long-term and 5-year survival than those patients without prostatic involvement. Similarly, prostatic stromal invasion and periprostatic/seminal vesical invasion had a similar, but much higher nodal metastasis and worse survival than patients with only prostatic CIS or urethral lamina propria invasion. In summary, presence of prostatic TCC involvement and levels of involvement are significant prognostic factors in patients with bladder cancer.     

Analysis of trefoil factor family protein 1 (TFF1, pS2) expression in chronic cholecystitis and gallbladder carcinoma

Trefoil factor family protein 1 (TFF1, pS2) interacts with mucins to protect gastrointestinal epithelium against injury and contributes to mucosal repair by promoting epithelial cell migration and restitution. Moreover, TFF1 has antiproliferative and anti-apoptotic effects and promotes cell scattering and invasion. We investigated TFF1 expression in healthy and inflamed non-neoplastic gallbladder mucosa as well as in gallbladder carcinomas (n=57) and corresponding metastases (n=18), using a tissue microarray technique. TFF1 immunoreactivity was absent in healthy mucosa, focally observed in epithelium with inflammatory changes and present in 35% of primary and 24% of metastatic cancer tissues. Immunoreactivity significantly decreased with increasing tumour stage (P=0.009) and increasing tumour grade (P=0.001). Patients with TFF1 positive tumours showed a more favourable outcome compared to patients with TFF1 negative tumours in univariate analysis (P=0.006). However, multivariate analysis proved resection status and tumour grade as the only independent prognostic factors. In conclusion, TFF1 is expressed in inflamed non-neoplastic gallbladder epithelium and in low stage and low grade gallbladder carcinomas. Thus, TFF1 may be the missing link between gallstones, chronic cholecystitis and gallbladder cancer. Further studies are needed to evaluate whether TFF1 immunostaining can be used as a diagnostic tool to identify patients with a more favourable outcome.     

Immunocytochemical localization of c-erbB-2 protein in transitional cell carcinoma of the urinary bladder

The level of expression and cellular localization of the c-erbB-2 gene product in transitional cell carcinoma of the urinary tract is controversial. Analysis of the c-erbB-2 gene structure and comparison of its expression in the same cells by Southern, Northern and immunoblotting, and by immunocytochemistry minimize the errors of interpretation inherent in one technique. Such a ‘correlative study’ has been performed on tumours from 82 patients, c-erbB-2 gene amplification was detected in 14 per cent of initial tumours and was associated with grade (.P< 0·001). Raised levels of mRNA were seen in those tumours with increased gene copy number and in 13 per cent of the remainder. Immunoblotting detected the expected 185 kD immunoreactive protein and a 155 kD piotein associated with high gene copy number. Immunocytochemistry localized c-erbB-2 immunoreactivity to the cell membrane and cytoplasm, and the latter predominated. Four antibodies to c-erbB-2 (AB-3, 21N, pAb 1, and NCL CB11) were compared on contiguous sections of the same tumour and showed the same pattern of immunoreactivity. Similarly, analyses carried out in three independent laboratories identified the same cellular localization. Membrane and cytoplasmic immunoreactivity was demonstrated in all tumours with gene amplification or increased mRNA levels and in 40 per cent of the remaining tumours. We showed that immunocytochemistry requires careful standardization of techniques and quantitation between different groups. However, despite variations in the intensity of immunoreactivity, the total number of positive cells remained constant. Therefore quantitation must be based on the number of positive cells and, ideally, their immunoreactive content relative to normal and positive tissue controls.     

沉默ABCG2对膀胱癌T24恶性生物学行为的影响

目的利用siRNA转染干扰沉默ATP结合盒式G型亚家族成员2（ABcG2）基因,并观察沉默前后T24恶性生物学行为的变化。方法siRNA沉默ABCG2后,观察T24增殖、克隆形成、迁移、侵袭、对放化疗抵抗、成干细胞球能力的影响。结果siRNA能够使ABCG2mRNA和蛋白质的表达下降80％左右,ABCG2被下调后,T24的增殖能力、克隆形成能力、迁移和侵袭能力、对放化疗的抵抗能力、成干细胞球的能力均下降（P〈0．05）。结论沉默ABCG2能够降低膀胱癌T24的恶性及干性,可以作为一个潜在的治疗靶点。     

转移相关蛋白1和埃兹蛋白在膀胱尿路上皮癌中的表达

目的 检测转移相关蛋白1(MTA-1)、埃兹蛋白(Ezrin)在膀胱尿路上皮癌(BUC)组织及正常膀胱黏膜组织中的表达,探讨两者与患者临床病理及预后之间的关系.方法 采用免疫组化法检测65例手术切除的BUC组织和30例正常膀胱黏膜组织中MTA-1和Ezrin蛋白表达,分析MTA-1和Ezrin在BUC中的表达与患者临床病理参数的关系,分析MTA-1和Ezrin表达之间的相关性和对患者预后的影响.结果 65例BUC组织中MTA-1和Ezrin阳性表达率分别为72.3%(47/65)和89.2%(58/65),30例正常膀胱黏膜组织MTA-1和Ezrin阳性表达率均为0,差异有统计学意义(均P＜0.01).BUC组织中,MTA-1表达与临床分期、肿瘤病理分级、有无转移、是否复发有关(均P＜0.01),Ezrin表达与临床分期、肿瘤有无转移、是否复发有关(均P＜0.01),MTA-1与Ezrin的表达呈正相关(r=0.742,P＜0.01).MTA-1和Ezrin联合表达组的无病生存率明显低于联合阴性表达组(P＜0.01).结论 MTA-1和Ezrin蛋白高表达与BUC发生发展、侵袭和转移有关.     

多发性浅表膀胱移行细胞癌中VEGF的表达及意义

目的:探讨单发性和多发性浅表膀胱移行细胞癌组织中血管内皮生长因子(VEGF)的表达及意义。方法:采用免疫组化方法对60例浅表膀胱移行细胞癌组织及10例正常膀胱组织进行血管内皮生长因子(VEGF)的检测,观察单发性和多发性浅表膀胱移行细胞癌组织中VEGF表达的关系。结果:多发性浅表膀胱移行细胞癌VEGF的高表达明显高于单发者的高表达;VEGF高表达的浅表膀胱移行细胞癌的患者的复发率明显高于低表达者的复发率。结论:VEGF表达的高低与浅表膀胱移行细胞癌的生物学行为有关。     

Expression of bcl-2 oncoprotein in renal cell tumours

Expression of bcl-2 is associated with inhibition of apoptosis and extension of cell survival. The importance of apoptosis in relation to the development and progression of renal cell neoplasia remains undefined so far. In order to determine the expression of bcl-2 oncoprotein in normal and neoplastic renal cells, 37 renal tumours were investigated by immunolabelling, including 13 clear cell carcinomas, ten tubulopapillary carcinomas, four chromophobic renal cell carcinomas, and ten oncocytomas. Twenty-six samples of adjacent normal renal tissue served as controls. bcl-2 expression was correlated with cell proliferation activity as estimated by Ki67 antigen expression, and p53 protein expression in the tumour samples. The results demonstrate that in the normal kidney, positive bcl-2 immunostaining was present in glomerular parietal epithelial cells, in distal tubular cells, and in sparse proximal tubule cells. Renal cell tumours showed heterogeneous bcl-2 expression according to the tumour cell type. While the majority of carcinomas of clear cell type were usually negative or contained sparsely distributed positive cells, all tubulopapillary carcinomas were consistently positive for bcl-2. In oncocytomas and chromophobic carcinomas, there was a low percentage of bcl-2 immunoreactive tumour cells; some nuclear bcl-2 positivity was detected in one chromophobic tumour. These findings indicate variable bcl-2 oncoprotein expression in different types of renal cell tumours, with the highest level of expression in tubulopapillary carcinomas. No clear relationship was found between nuclear grade, cell proliferation activity, and level of bcl-2 expression. p53 protein was detected in only one tubulopapillary carcinoma.     

Distribution of S-100 protein-positive dendritic cells and expression of HLA-DR antigen in transitional cell carcinoma of the urinary bladder in relation to tumour progression and prognosis

The distribution of S-100 protein positive dendritic cells (S100-DCs) in cancer nests and the expression of HLA-DR antigen on cancer cells in 90 patients with transitional cell carcinoma of the urinary bladder were studied immunohistochemically. A dense infiltrate of S100-DCs (more than 10 S100-DCs/high power field) was detected in 47 out of 90 cases, while in the remaining tumours the infiltrate was sparse. HLA-DR positive cancer cells (DR-CCs) were detected in 24 cases, including 16 with dense DR-CCs (more than 100 DR-CCs/high power field); no expression was observed in the remaining tumours. In terms of the numbers of S100-DCs infiltrating the following statistically significant differences were observed: tumour grading G1>G3, depth of penetration pT0>pT3; (p<0.05), G2>G3, lymphatic invasion->+ and venous invasion ->+; (p<0.01). A multivariate analysis demonstrated that the most important factor affecting prognosis was distant organ and/or lymph node metastasis (p<0.01) the number of S100DCs, with a hazard ratio (HR) of 0.26 (p<0.01), and the number of DR-CCs with HR of 0.18 (p<0.05); these were statistically significant. S100-DCs and DR-CCs may be regarded as independent prognostic factors of tumour growth and progression.     

pS2 (TFF1) expression in prostate carcinoma: correlation with steroid receptor status

pS2 or TFF1 is a member of the trefoil factor family, which is distributed throughout the gastrointestinal tract in both normal and diseased tissues. It is also considered to be one of the major estrogen‐regulated proteins and an indicator of estrogen receptor (ER) functionality. pS2 has previously been investigated in benign and malignant prostate lesions with little information about its relationship to steroid receptor status. Our purpose was to correlate pS2 expression with steroid receptor status (ER alpha and progesterone receptor (PR)) and other pathologic variables in prostate carcinoma. 15 benign prostate hyperplasia (BPH) and 47 prostate carcinoma cases were investigated by means of immunohistochemistry for pS2, ER and PR expression. 80% of BPH showed pS2 cytoplasmic immunoreactivity in hyperplastic acini and about half of these cases also exhibited nuclear staining decorating basal or both basal and luminal nuclei. pS2 was highly expressed in prostate carcinoma (91.4%) with both cytoplasmic and nuclear patterns of staining. The latter pattern was significantly associated with carcinoma having a low Gleason score (p=0.02). pS2 lacked any significant correlation with steroid receptor status, stage or grade. Univariate survival analysis revealed a significant impact of stage (p=0.03) and nodal status (p<0.0001) on patient outcome. The diagnostic value of pS2 expression in prostate carcinoma validated 74.19% accuracy, 91.48% sensitivity and 78.18% positive predictive value. The high sensitivity of pS2 expression in prostate carcinoma could make it a suitable marker for diagnosis of prostate carcinoma, especially in metastatic cases of unknown origin. The absence of correlation and dissimilarity in immunolocalization between pS2 and ER alpha leads to the assumption that ER alpha could not be the regulatory protein for pS2 and may raise questions about the functionality of ER alpha in prostate. The nuclear pattern of pS2 immunoreactivity either in benign or malignant prostatic lesions is similar to the published data on ER beta distribution and could also identify a subset of carcinoma patients with a favorable prognosis.     

膀胱移行细胞癌中p16基因的改变

目的 明确ｐ１６基因在膀胱移行细胞癌中的改变。方法 采用Ｓｏｕｔｈｅｒｎ杂交、聚合酶链反应－单链构象多态性分析（ＰＣＲ－ＳＳＣＰ）及ＤＮＡ甲蜞化分析技术分别检测５２例膀胱移行细胞癌中ｐ１６基因的缺失、突变及５′ＣｐＧ岛甲基化。结果 ５２例膀胱移行细胞癌中１１例（２１．５％）存在ｐ１６基因的缺失;仅１例肿瘤于ｐ１６基因外显子２出现点突变;１９例（３６．５％）肿瘤发现ｐ１６基因５′ＣｐＧ岛甲基化。结     

Expression of HLA class I-encoded cell surface antigens in transitional cell carcinoma of the urinary bladder

Abstract: I. Levin, B. Klein, S. Segal, A. Eyal, J. Gopas, J. Kaneti, M. Saadon, O. Kuperman. Expression of HLA class I-encoded cell surface antigens in transitional cell carcinoma of the urinary bladder.     

Expression of c-myc protein is related to cell proliferation and expression of growth factor receptors in transitional cell bladder cancer

Archival biopsy specimens from transitional cell bladder tumours (n=185) were analysed immunohistochemically for expression of c-myc protein. The results were compared with compared with histopathological and clinical parameters and survival. Forty-three per cent of the tumours were negative for c-myc protein and weak, moderate, or strong cytoplasmic expression was found in 34, 14, and 9 per cent of cases, respectively. Nuclear positivity for c-myc protein was detected in 35 per cent of tumours and nuclear opositivity was related to overexpression of c-erb B-2 (P=0.01) and a high proportion of nuclei were also positive for p53 oncoprotein (p<0.05). Cytoplasmic expression of c-myc protein was related to histological grade (P=0.005), papillary status (P=0.007), the S-phase fraction (P=0.008), the mitotic index (P=0.021), overexpression of epidermal growth factor receptor (P=0.045), and c-erb B-2 (P=0.17). Expression of c-myc protein was not significantly related to the progression of tumours and it had no prognostic value in survival analysis. Independent predictors were the T-category (P<0.001), papillary status. (P=0.001), and S-phase fraction (P=0.061). The results show that while c-myc gene product participates in growth regulation of human bladder cancer cells, it has no independent prognostic significance.     

Can cytomorphometry replace histomorphometry for grading of bladder tumours?

Summary Cytomorphometry, using various cytopreparatory techniques on bladder washings and histomorphometry on the resected bladder tumours, was used in an attempt to answer the question: Can cytomorphometry replace histomorphometry for grading of bladder tumours? For the analysis of quantitative data, a probit model was used. Three out of the four cytomorphometric methods provided data supportive to the histomorphometry Using one of the four cytomorphometric methods was sufficient to enhance grading accuracy and all were equally good. Two cases of high grade carcinoma in situ were properly identified by cytomorphometry (as judged on the follow-up data) but the concurrent resected papillary tumours were low grade. These findings indicate that cytomorphometry is a useful method in bladder tumour grading. In some cases it is preferable to histomorphometry.