Abnormal Expression Of E-cadherin Research Articles

Expression of E-Cadherin and α-, β-, γ-Catenin Proteins in Endometrial Carcinoma

Loss of the cell adhesion molecule E-cadherin is suggested to promote tumor invasion and distant metastasis in tumor development. Recently, it has been proposed that E-cadherin function requires its linkage to the cytoskeleton through catenins. We evaluated the expression of E-cadherin and alpha-, beta-, gamma-catenins in tissues of human endometrial carcinoma, analyzed the patterns of cell adhesion molecules' expression in endometrial carcinoma and investigated the relationship between the statuses of cell adhesion molecules and various clinicopathological factors. This study investigated the immunohistochemical expression of E-cadherin and alpha-, beta-, gamma-catenins in 33 paraffin embedded formalin fixed tissues of endometrial carcinomas. Aberrant E-cadherin, and alpha-, beta-, gamma-catenin expression was observed in 33.3 (11 of 33), 27.3 (9 of 33), 18.2 (6 of 33), and 51.5 (17 of 33) % of the specimens, respectively. Statistically significant correlation was found between aberrant expression of E-cadherin and lymph node metastasis and cell types other than endometrioid adenocarcinoma. Aberrant pattern of gamma-catenin expression was also correlated with deep myometrial invasion. However, alpha-, and beta-catenin expression was not correlated with any clinicopathological parameters. Using the Kaplan-Meier method and log-rank comparison test, abnormal expression of E-cadherin was correlated closely with poor survival (p < 0.05), but cases with loss of both E-cadherin and catenin expression predicted even poorer survival than cases with only one or no aberrant expression in E-cadherin and catenins. We revealed aberrant expression of these cell adhesion molecules among patients with endometrial carcinoma. Aberrant expression of E-cadherin was correlated with lymph node metastasis and cell types other than endometrioid adenocarcinoma, while aberrant expression of gamma-catenin was related with deep myometrial invasion. The expression of E-cadherin might be a possible prognostic factor for endometrial cancer while the expression of catenins may help predict patient's survival.

Abnormal immunoreactivity of the E-cadherin/catenin (alpha-, beta-, and gamma-) complex in premalignant and malignant non-melanocytic skin tumours.

E-cadherin/catenin (alpha-, beta-, and gamma-) complex plays a critical role in the control of epithelial differentiation. The aim of this study was to examine the immunoreactivity of E-cadherin and alpha-, beta-, and gamma-catenins in premalignant and malignant non-melanocytic skin tumours (NMST) and to correlate their expression with the grade of tumour differentiation, as assessed by the established histopathological criteria and by the Ki-67 index. Benign NMSTs were also studied. To investigate any possible influence of immunosuppression in the expression of E-cadherin and catenins, the study compared tumours obtained from renal transplant recipients (RTRs) and immunocompetent patients. Immunoperoxidase staining of E-cadherin and alpha-, beta-, and gamma-catenins was performed in 42 squamous cell carcinomas (SCCs) (26 from RTRs and 16 from non-RTRs), 30 lesions of Bowen's disease (11 from RTRs and 19 from non-RTRs), 11 atypical squamoproliferative lesions from RTRs, 19 actinic keratoses (9 from RTRs and 10 from non-RTRs), and 20 viral warts from RTRs. The findings of this study were as follows. Firstly, the probability of abnormal expression of E-cadherin and alpha-, beta-, and gamma-catenins increased from benign to premalignant and malignant NMSTs (p<0.001 for all). Secondly, there was agreement in abnormal expression between most of the molecules measured in malignant and premalignant NMSTs (p<0.05). Thirdly, in SCC, abnormal expression of E-cadherin and catenins was more frequent in lesions with a high (>40%) Ki-67 index than in those with a low Ki-67 index (<40%) (p=0.003). However, only the abnormal expression of gamma-catenin increased with the grade of SCC differentiation (p=0.008). Fourthly, abnormal expression of gamma-catenin predicted a high proliferation index (Ki-67 index 40%) in NMSTs (p<0.01, OR=6.19). Finally, there was no difference in the abnormal expression of E-cadherin and catenins between NMSTs from immunosuppressed and immunocompetent patients. Thus, abnormal expression of the E-cadherin/catenin complex was quite common in SCC and Bowen's disease and also in a proportion of intraepithelial dysplastic lesions, such as atypical squamoproliferative lesions and actinic keratosis, suggesting that these changes may be early indicators of the neoplastic process. Abnormal expression of gamma-catenin was the sole predictor of high proliferation in NMST and was also correlated with the tumour grade, suggesting a possible important role for gamma-catenin in tumourigenesis.

Abnormal E-cadherin expression and prostate cell blood dissemination as markers of biological recurrence in cancer

Until now, no molecular parameter has been available for predicting the metastatic potential of prostate tumours, which leaves their outcome uncertain despite an apparent benign histology or early stage. Abnormal expression of adhesion molecules, such as E-cadherin, can be contributing factors for increased invasiveness and metastatic potential. Histological analysis for E-cadherin expression was carried out on paraffin-embedded tumour tissues. Tumour metastatic potential was indirectly evaluated by detecting circulating prostate cells (CPC), using reverse transciptase-polymerase chain reaction (RT-PCR) and prostate-specific membrane antigen (PSMA) as a target. Patients were followed-up for a median of 14 months (range 10–19 months) after surgery with serum prostate-specific antigen (PSA) level measurement. Interestingly, 23 of 44 localised tumours exhibited aberrant E-cadherin expression. Prior to primary surgery, PSMA RT-PCR detected the spread of prostate cells to the blood in 24 patients. Statistical analysis showed that abnormal E-cadherin expression in the tumours was the only variable that was independently correlated with prostate cell dissemination in the blood ( P<0.0001). In logistic regression analysis, abnormal E-cadherin expression was a significant independent predictor for a later biological relapse. This impaired adhesion status was clearly correlated with a haematogenous spread of the primary tumour cells. It could therefore be an objective way to restrict the indications for radical surgery to patients not presenting with this feature.

Immunohistochemical Evaluation of Cadherin and Catenin Expression in Early Gastric Carcinomas: Correlation with Clinicopathologic Characteristics and Helicobacter pylori Infection

Dysfunction of E-cadherin and catenin has been linked to invasiveness and differentiation of tumors. This study aimed to characterize the expression of cadherins and catenins in early gastric carcinoma and their relationship to clinicopathologic characteristics and Helicobacter pylori infection. E-cadherin and α-, β- and γ-catenins were strongly expressed in normal epithelium but abnormal immunoreactivity of at least one of these four proteins was noted in 48 (90.6%) of 53 early gastric carcinomas. Only 5 cases with intestinal-type tumors had intact expression of E-cadherin and α-, β-, and γ-catenins. Abnormal immunoreactivity in the tumor tissue was observed in 18 patients (34.0%) for E-cadherin, in 35 (66.0%) for α-catenin, in 20 (37.7%) for β-catenin, and in 37 (69.8%) for γ-catenin. In diffuse-type tumors, abnormal expression of E-cadherin (60.9 vs. 13.3%, p < 0.0005), α-catenin (82.6 vs. 53.3%, p < 0.05) and γ-catenin (91.3 vs. 53.3%, p < 0.005) was more frequent than in the intestinal type. Ten tumors with lymph node metastasis showed a relatively higher frequency of abnormal expression of E-cadherin (70 vs. 25.6%, p < 0.05) but a lower frequency of abnormal expression of β-catenin (10 vs. 44.1%, p = 0.07) than those without metastasis. No significant association was found between cadherin/catenin expression and the depth of invasion or the H. pylori status. It was concluded that abnormal expression of E-cadherin and the catenin-mediated cell-cell adhesion system occurs frequently in early gastric carcinogenesis and may play an important role in the genesis of histologic differentiation and in the mode of metastasis of early gastric carcinomas.

E-CADHERIN IMMUNOSTAINING OF BLADDER TRANSITIONAL CELL CARCINOMA, CARCINOMA IN SITU AND LYMPH NODE METASTASES WITH LONG-TERM FOLLOWUP

We analyze the expression of E-cadherin in bladder transitional cell carcinoma, areas of carcinoma in situ and lymph node metastases, and determine the value of E-cadherin immunoreactivity for predicting disease progression and survival of patients with bladder transitional cell carcinoma. The study group consisted of 77 patients who underwent radical cystectomy. Formalin fixed paraffin sections were processed with a hot, citric acid antigen retrieval method, followed by immunostaining with anti-E-cadherin monoclonal antibody and a standard avidin biotin complex technique. E-cadherin expression was also evaluated in carcinoma in situ sections (18) and in regional lymph node metastases (17). Loss of normal membrane E-cadherin immunoreactivity was found in 59 (77%) patients. Abnormal expression of E-cadherin was associated with muscle invasive disease (p = 0.010) and lymph node metastasis (p = 0.044). Of the 18 carcinoma in situ specimens 15 (83%) and of the 17 metastatic lymph nodes 13 (76%) had abnormal E-cadherin expression. Concordance rates of E-cadherin status in carcinoma in situ areas and metastatic lymph nodes with the primary tumors were 85% and 88%, respectively. At a median followup of 128 months, abnormal E-cadherin expression was significantly associated with disease progression (p = 0.0219) and bladder cancer specific survival (p = 0.037). E-cadherin expression and pathological stage but not grade were independent predictors of disease progression (p = 0.042, 0.047 and 0.158, respectively). In bladder cancer altered E-cadherin expression is associated with the degree of invasiveness, lymph node metastasis and increased risk of death from bladder cancer. Furthermore, E-cadherin status is an independent predictor of disease progression in patients treated with cystectomy for transitional cell carcinoma of the bladder.

E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder

Objectives. The clinical course of carcinoma in situ (CIS) of the bladder is highly variable. Our objective in this study was to describe E-cadherin expression patterns in CIS with and without papillary disease and to determine whether altered E-cadherin expression is associated with disease progression and survival in patients with CIS of the bladder. Methods. Tumor specimens from 53 patients who had CIS in the absence of muscle-invasive carcinoma on bladder biopsy were identified. Formalin-fixed paraffin sections were processed using a hot citric acid antigen retrieval method, followed by immunostaining with anti-E-cadherin monoclonal antibody. Expression patterns were evaluated in a blinded fashion and scored as normal and abnormal, which included absent and various degrees of heterogeneous immunostaining. Outcomes analyzed were recurrence, progression, and survival. Results. Loss of normal membrane E-cadherin immunoreactivity was found in 17 patients (32%). At a median follow-up of 131 months, abnormal E-cadherin expression was significantly associated with disease recurrence ( P = 0.0087), disease progression ( P = 0.0003), and bladder cancer-specific survival ( P = 0.0285). In multivariate analyses, E-cadherin expression was independently associated with disease recurrence ( P = 0.019, 95% confidence interval [CI] 1.342 to 5.940), disease progression ( P = 0.002, 95% CI 2.049 to 17.989), and bladder cancer-specific survival ( P = 0.025, 95% CI 1.179 to 10.432). Conclusions. Loss of E-cadherin expression in patients with CIS with and without papillary disease of the bladder predicts disease recurrence, disease progression, and bladder cancer-specific death. CIS with and without papillary disease associated with abnormal E-cadherin expression may represent a biologically more aggressive cancer, requiring early definitive therapy. This hypothesis should be evaluated in larger studies and prospective clinical trials.

Distinction of differentiated type early gastric carcinoma with gastric type mucin expression

BACKGROUND Intestinal and diffuse gastric carcinomas differ in morphology and growth behavior. Differentiated type gastric carcinoma (DGC), which corresponds roughly with the intestinal type of Lauren, can demonstrate phenotypic properties associated with mucin expression and brush border. However, their clinical significance is controversial. A classification based on mucin phenotype and brush border was performed to determine the clinicopathologic diversity of DGCs in their early stage. METHODS A total of 120 specimens from 116 DGC patients with definite submucosal invasion were evaluated both macroscopically and histologically. All sections were examined immunohistochemically with human gastric mucin, Muc-2, and CD10 and with mucin histochemically with paradoxical concanavalin A staining and high iron Diamine-Alcian Blue. They were classified into gastric type (G-type), intestinal type (I-type), mixed gastric and intestinal type (M-type), or null type (N-type) phenotypes. The immunoreactivity of E-cadherin and β-catenin also was investigated to determine the correlation between mucin phenotype and clinicopathologic factors. RESULTS The G-type phenotype was found to be in contrast to I-type: G-type was an independent factor associated with lymph node metastasis. Significant correlations were observed between the G-type phenotype and the complex type carcinoma found that was histologically: lymphatic invasion, lymph node metastasis, and the abnormal expression of E-cadherin. A significant difference in the proportion of mucin phenotypes between papillary type and tubular type carcinoma was observed. G-type was found to be the predominant phenotype in papillary carcinoma in contrast to tubular carcinoma. CONCLUSIONS The G-type mucin phenotype and papillary adenocarcinoma should be distinguished from other types of DGCs because of their increased malignant potential in the incipient phase of invasion and metastasis. The significance of G-type and papillary adenocarcinoma should be reflected in the treatment of patients with early stage DGCs, including endoscopic mucosal resection. Cancer 2000;89:724–32. © 2000 American Cancer Society.

Distinction of differentiated type early gastric carcinoma with gastric type mucin expression

Intestinal and diffuse gastric carcinomas differ in morphology and growth behavior. Differentiated type gastric carcinoma (DGC), which corresponds roughly with the intestinal type of Lauren, can demonstrate phenotypic properties associated with mucin expression and brush border. However, their clinical significance is controversial. A classification based on mucin phenotype and brush border was performed to determine the clinicopathologic diversity of DGCs in their early stage. A total of 120 specimens from 116 DGC patients with definite submucosal invasion were evaluated both macroscopically and histologically. All sections were examined immunohistochemically with human gastric mucin, Muc-2, and CD10 and with mucin histochemically with paradoxical concanavalin A staining and high iron Diamine-Alcian Blue. They were classified into gastric type (G-type), intestinal type (I-type), mixed gastric and intestinal type (M-type), or null type (N-type) phenotypes. The immunoreactivity of E-cadherin and beta-catenin also was investigated to determine the correlation between mucin phenotype and clinicopathologic factors. The G-type phenotype was found to be in contrast to I-type: G-type was an independent factor associated with lymph node metastasis. Significant correlations were observed between the G-type phenotype and the complex type carcinoma found that was histologically: lymphatic invasion, lymph node metastasis, and the abnormal expression of E-cadherin. A significant difference in the proportion of mucin phenotypes between papillary type and tubular type carcinoma was observed. G-type was found to be the predominant phenotype in papillary carcinoma in contrast to tubular carcinoma. The G-type mucin phenotype and papillary adenocarcinoma should be distinguished from other types of DGCs because of their increased malignant potential in the incipient phase of invasion and metastasis. The significance of G-type and papillary adenocarcinoma should be reflected in the treatment of patients with early stage DGCs, including endoscopic mucosal resection.

Prognostic significance of E-cadherin/catenin complex expression in gastric cancer.

Abnormal expression of E-cadherin/catenin complex in cancer has been associated with poor differentiation and acquisition of invasiveness, suggesting a possible role of this protein as an invasion suppressor. In this study, we conducted an immunohistochemical investigation of all components of the E-cadherin/catenin complex in 65 gastric cancer patients. Abnormal expression of E-cadherin and, alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal type of gastric cancer, and correlated with poor differentiation. Abnormal expression of E-cadherin and beta-catenin correlated with poor survival. Abnormal expression of all four components of the complex was associated with poorly differentiated and diffuse-type carcinoma, and poor survival. In the multivariate analysis, abnormal expression of the E-cadherin/catenin complex was not an independent prognostic factor. These results suggest that the E-cadherin/catenin complex may be a useful marker of differentiation and prognosis in gastric cancer. Further studies are warranted to clarify the impact of the E-cadherin/catenin complex on prognostic factor of gastric cancer.

Expression of the E-cadherin/catenin (alpha-, beta-, and gamma-) complex correlates with the macroscopic appearance of early gastric cancer.

E-cadherin and its associated cytoplasmic proteins, alpha-, beta-, and gamma-catenins, play an essential role in the control of epithelial differentiation. We have previously shown that loss or down-regulation of E-cadherin/catenin correlates with poor survival in advanced gastric adenocarcinoma. The aim of this study was to assess the expression of E-cadherin and catenins in early gastric cancers (EGCs). Immunohistochemical staining for E-cadherin and alpha-, beta-, and gamma-catenins was performed on 41 paraffin-embedded gastrectomy specimens of EGC using an indirect immunoperoxidase technique. The pattern of expression and cellular localization of the E-cadherin/catenin complex in tumour cells were correlated with the macroscopic appearance of the tumour according to the Japanese Endoscopic Society classification. The tumours were classified as follows: three type I (protruding) and 38 type II (superficial), of which ten were type IIa (elevated), one was type IIb (flat), and 27 were type IIc (depressed). E-cadherin and alpha-, beta-, and gamma-catenins were expressed at the cell-cell junctions in normal mucosa. Forty out of 41 tumours showed abnormal expression (loss of membranous immunoreactivity and/or nuclear staining) of at least one component of the E-cadherin catenin complex. Loss of E-cadherin immunoreactivity was more frequently seen in type IIb (1/1, 100%) and type IIc (27/27, 100%) than in type I (1/3, 33%) and type IIa (1/10, 10%) (p<0.01). Abnormal expression of E-cadherin and alpha-catenin was more frequently seen in diffuse-type than in intestinal type tumours (p<0.05). Abnormal immunoreactivity of beta- and gamma-catenin, including nuclear localization, was observed in 34% and 7.3% of tumours, respectively, but there was no significant correlation with tumour type or endoscopic appearance. In conclusion, abnormal expression of the E-cadherin/catenin complex occurs in EGC and seems to correlate with macroscopic appearances.

Malignant progression in Barrett's esophagus: pathology and molecular biology.

Due to its increasing incidence, esophageal adenocarcinoma and its precursor lesions have received increasing attention in recent years. The histopathologic steps in the process of malignant progression in Barrett's esophagus are well described and include the following: (a) metaplasia of the normal esophageal squamous epithelium to a specialized intestinal glandular epithelium, (b) development of dysplasia (classified histologically as low and high grade), and (c) development of adenocarcinoma characterized by invasive and metastatic potential. Intestinal metaplasia can be identified by the presence of goblet cells, the detection of which can be aided by finding mucin stained by Alcian blue at low pH. Despite this well-characterized sequence, the timing of the development of dysplasia and the subsequent transition to carcinoma and the risk of development of carcinoma in low- and high-grade dysplasia are not precisely known. In addition, there are problems in the identification of dysplasia, including sampling error and interobserver discrepancies among pathologists. A better understanding of the mechanisms of these events would allow early identification and elimination of high-risk lesions before adenocarcinoma with its attendant poor prognosis were able to develop. In order to better understand this process and to potentially identify early markers of malignant transformation, a variety of molecular studies have been carried out in recent years on adenocarcinoma and its precursor lesions in Barrett's esophagus. On the phenotypic level, increased expression and changes in pattern of expression of proliferation marker (Mib-1) Ki-67 antigen, overexpression of p53 protein, overexpression of growth factors such as epidermal growth factor (EGF), c-erbB2, and transforming growth factor (TGF)-a, decreased and abnormal expression of the cell adhesion molecule E-cadherin, and, in carcinomas, increased expression of serine proteases have all been described. A new area of interest is the family of rab proteins, which play an important role in maintaining cell polarity in the gastrointestinal tract. Increased expression of one of these proteins, rab11, has been described in low-grade, but not high-grade dysplasia. In cytogenetic studies, an increased S-phase fraction, followed by an increased tetraploid (4N) fraction and then aneuploidy, has been described. So far, the specific genes which have been most thoroughly investigated have been p53, APC, p16, and the sites of probable tumor suppressor genes, including 3p (FHIT), 13q, and 18q. With only a few exceptions (i.e., rab11 expression, and possibly mutations of FHIT), the numerous molecular abnormalities which have been described occur late in malignant progression, which means that the best marker which presently exists to identify high-risk lesions in Barrett's esophagus is the histologic identification of dysplasia in endoscopic biopsies, especially high-grade dysplasia. We are presently beginning studies using laser microdissection and competitive genomic hybridization (CGH), which could help to identify new chromosomal areas that might contain genes that are crucial in the early phases of malignant progression in Barrett's esophagus. In the future, identification of such early molecular events which predispose to carcinoma development will allow more precise and earlier risk assessment for individual patients, therefore, enabling more effective therapy.

Downregulation and abnormal expression of E-cadherin and β-catenin in nasopharyngeal carcinoma: Close association with advanced disease stage and lymph node metastasis

Nasopharyngeal carcinoma (NPC) is predominantly of the undifferentiated histological subtype. Histological differentiation is of limited prognostic significance in NPC. Recent studies have suggested that downregulation of the cadherin-catenin cell adhesion complex may play a crucial role in the initial stage of cancer invasion and metastasis and is associated with poor prognosis in human cancers. Expression of E-cadherin has not been reported previously in NPC, and its prognostic value in NPC is unknown. The purpose of this study was to examine the expression pattern of E-cadherin and its associated partner, β-catenin, in NPC and their possible applications as prognostic markers to predict the clinical outcome of NPC. Expression of the E-cadherin and β-catenin was examined by immunohistochemical methods in 74 cases of primary NPC and 17 of their corresponding lymph node metastases. Normal nasopharyngeal epithelium showed strong and homogeneous immunocytochemical staining of E-cadherin and β-catenin at the cell membranes and intercellular junctions. In contrast, primary NPC showed variable and heterogeneous staining patterns of E-cadherin and β-catenin. Loss of membranous E-cadherin expression was significantly associated with advanced stages of diseases ( P < .001). Eighty percent to ninety percent of NPC in stages IV and V (Ho's staging), respectively, showed a reduced (<35%) membranous staining of E-cadherin compared with normal nasopharyngeal epithelium. Expression of β-catenin also was downregulated in advanced NPC. Ninety percent to one hundred percent of NPC in stages IV and V (Ho's staging) expressed a reduction (<35%) of immunocytochemical staining of β-catenin. The expression pattern of β-catenin staining was strongly associated with the expression of E-cadherin ( P < .001). Unlike E-cadherin, nuclear staining of β-catenin expression was observed in some of the primary NPC and lymph node metastasis. Reduced expression of E-cadherin and β-catenin expression was associated with a shorter survival of NPC patients ( P < .001). In advanced NPC patients (stages IV and V), a significant difference in survival was observed in tumors with higher or lower levels of E-cadherin expression ( P = .0224, log-rank test). These observations suggests that expression of E-cadherin and β-catenin may have prognostic values in NPC patients.

Abnormal Expression of the E-cadherin-catenin Complex in Dysplastic Barrett's Oesophagus

It is now accepted that altered E-cadherin-catenin complex expression in oesophageal cancer correlates with clinical and pathological parameters, while abnormal E-cadherin expression occurs early in Barrett's oesophagus. We evaluated immunohistochemically the expression and cellular localization of alpha-, beta-, and gamma-catenin, and E-cadherin in 5 dysplastic and 26 non-dysplastic cases of Barrett's oesophagus. Usually all three catenins were localized at the cell membrane, as was E-cadherin. A similar staining pattern for E-cadherin and the catenins was observed in all cases of non-dysplastic Barrett's syndrome. However, 60% (3/5) of cases with dysplasia showed loss of membranous beta-catenin staining and diffuse cytoplasmic distribution, with predominantly nuclear localization in two cases. Membranous staining and concomitant cytoplasmic localization of E-cadherin, alpha-catenin and gamma-catenin were seen in one case with abnormal beta-catenin immunoreactivity. Our results indicate that altered subcellular distribution of beta-catenin occurs frequently in dysplastic Barrett's oesophagus and possibly reflects the signalling function of this molecule.

DETECTION OF ABNORMAL E-CADHERIN EXPRESSION BY SIMULATED PROSTATE BIOPSY

Purpose Sampling error is an inherent problem of prostate biopsy. Consequently the determination of whether a given carcinoma is clinically significant based on biopsy results is problematic. We assess the dimensions of sampling error and, thereby, provide insight into the potential value of prognostic markers applied to needle biopsies. Materials and Methods We constructed 3-dimensional computer models of 21 prostatectomy specimens, including outlines of carcinomas, regions of abnormal E-cadherin expression and individual Gleason patterns. The 6 random systematic core biopsy technique and modifications were simulated using a computer algorithm. Results In 6 of 21 cases the area of abnormal E-cadherin expression and/or high grade carcinoma was not sampled on 6 random systematic core biopsy. The areas missed were either small or inconsistently under sampled regions of the prostate. Modifying the placement of biopsy needles improved the detection of these features. In addition, percent tumor in the needle appeared to be well correlated to percent tumor in the prostate (r = 0.891, r ( 2) = 0.642). Conclusions To avoid underestimating the aggressiveness of prostatic carcinoma at least 6 biopsies should be taken from each patient. A more extensive sampling is probably not warranted in all patients but it may prove useful in those in whom extent of disease is unclear or whose general health makes treatment decisions difficult. A reliable estimate of tumor volume in the prostatectomy specimen can be made based on relative amount of tumor in the biopsy specimen on an individual basis.

E-Cadherin Expression Is Correlated with the Isolated Cell/Diffuse Histotype and with Features of Biological Aggressiveness of Gastric Carcinoma

We studied the pattern of immunohistochemical expression of E-cadherin in a series of 50 gastric carcinomas, aiming to analyze its relationship with histotype and features of biological aggressiveness of the tumors and survival of the patients. Abnormal E-cadherin expression was significantly (p=.0007) higher in diffuse/isolated-cell type carcinomas than in intestinal/glandular carcinomas. In mixed carcinomas abnormal E-cadherin expression in the diffuse/isolated-cell-type component (94.4%) was significantly (p=.007) higher than in intestinal/glandular component (55.6%). Significant relationships were observed between abnormal E-cadherin expression and nodal metastases (p=.004) and pTNM stages (p=.05). Survival of patients with tumors displaying abnormal E-cadherin expression was worse than that of patients with tumors presenting normal expression, though not attaining the threshold of statistical significance (p=.l9). We conclude that abnormal E-cadherin expression is correlated with diffuse/isolated-cell histotype and features of biological aggressiveness of gastric carcinoma.

E-Cadherin and Integrin Cell Adhesion Molecule Expression in Invasive andin SituCarcinoma of the Cervix

Integrin and E-cadherin cell adhesion molecules are important in the maintenance of normal epithelial structures, and altered expression of these molecules may be important in epithelial tumors, particularly in the processes of invasion and metastasis. This study examines the immunohistochemical expression of the α2β1, α3β1, α6, and β4 integrins and of E-cadherin in high-grade cervical intraepithelial neoplasia (CIN) and in invasive carcinoma of the cervix. Abnormal expression of E-cadherin and of all of the integrin subunits examined was detected in the dysplastic epithelium in CIN in the majority of cases, but in a minority of cases this expression was lost in the superficial layers of the dysplastic epithelium. Diffuse expression of E-cadherin and of all of the integrins was seen in the majority of cases of invasive cervical carcinoma. Abnormal expression of integrin cell adhesion molecules occurs in the majority of cases of high-grade CIN, and E-cadherin expression is retained in the dysplastic epithelium. Diffuse expression of integrins and of E-cadherin also occurs in invasive carcinoma, but as the expression pattern was similar in all cases of carcinoma, no correlation with outcome is possible and the significance of this expression is unclear.

Loss of membranous E‐cadherin expression in pancreatic cancer: Correlation with lymph node metastasis, high grade, and advanced stage

Epithelial cadherin (E-cadherin) is a Ca(2+)-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumors. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumors (grade I) (4/14, 28 per cent) (P = 0.012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P = 0.043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer.

Molecular prognostic factors in bladder cancer.

In this paper the predictive value of molecular prognostic parameters for bladder cancer is discussed. DNA ploidy has additional prognostic value for grade 2 tumors, irrespective of stage, with aneuploid tumors having a poor prognosis. Overexpression of the epidermal growth factor receptor (EGFR) can be used as a prognostic factor for the group of superficial tumors. Both abnormal E-cadherin and retinoblastoma (RB) expression have additional prognostic value for invasive tumors. The exact predictive value for the superficial tumors needs further study. The results with respect to p53 are conflicting and its exact role especially in the progression of pT1g3 tumors has to be clarified. In view of the discordance concerning its prognostic value, c-erbB-2 overexpression also needs further study. It appears that at this moment only a few molecular markers seem to have potential prognostic value, but their precise clinical relevance has to be studied more extensively. In particular the value of progression markers in the superficial TCC needs more attention.