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.

Ohene-Abuakwa Y ，Noda M ，Perenyi M ，Kobayashi N ，Kashima K ，Hattori T ，Pignatelli M ... -  《JOURNAL OF PATHOLOGY》

An immunohistochemical examination of the expression of E-cadherin, alpha- and beta/gamma-catenins, and alpha2- and beta1-integrins in invasive breast cancer.

This study examines the expression of the cell-cell adhesion molecules E-cadherin and its associated proteins, the catenins and the matrix-cell adhesion molecules beta1- and alpha2-integrins, in primary invasive breast carcinoma. Expression was assessed immunohistochemically on frozen sections by semi-quantitative scoring of the intensity and proportion of immunoreactivity in 55 cases. Associations with each other and with other histological and prognostic features and survival were sought. There was a significant association between loss of E-cadherin expression and loss of alpha- and beta/gamma-catenin immunostaining. In 20 per cent of cases, membranous immunoreactivity with E-cadherin antibody was absent. Absent cytoplasmic expression of alpha- and beta/gamma-catenins was seen in 24 and 22 per cent of breast cancers, respectively. The intensity of reactivity with E-cadherin showed a significant association with histological grade (p=0.002) and tumour type (p<0.001). Lobular carcinomas frequently showed loss of expression of E-cadherin, as reported elsewhere; loss of catenin expression was also found in these tumours. alpha-catenin intensity also showed a relationship with grade (p=0.008) and with oestrogen receptor (ER) status (p=0.006). beta/gamma-catenin expression was not associated with other known prognostic factors. Forty-nine per cent and 42 per cent of cases showed no membrane immunostaining with beta1- and alpha2-integrin, respectively, and co-ordinated loss of beta1- and alpha2-integrin expression was found. Both beta1- and alpha2-integrin expression were associated with histological grade (p=0.003 and p=0.031, respectively) and beta1 immunoreactivity with tumour type (p=0.010). None of the variables examined showed a statistically significant association with tumour size or lymph node stage, or with overall survival, although a trend was seen (p=0.087) towards poorer survival of patients with tumours with absent or weak expression of beta1-integrin. The expression of these markers is of biological interest, but appears to be of little additional use in predicting clinical behaviour.

Gonzalez MA ，Pinder SE ，Wencyk PM ，Bell JA ，Elston CW ，Nicholson RI ，Robertson JF ，Blamey RW ，Ellis IO ... -  《JOURNAL OF PATHOLOGY》

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.

Papadavid E ，Pignatelli M ，Zakynthinos S ，Krausz T ，Chu AC ... -  《JOURNAL OF PATHOLOGY》

Abnormal expression of E-cadherin and beta-catenin may be a molecular marker of submucosal invasion and lymph node metastasis in early gastric cancer.

Tanaka M ，Kitajima Y ，Edakuni G ，Sato S ，Miyazaki K ... -  《BRITISH JOURNAL OF SURGERY》

E-cadherin and alpha-, beta-, and gamma-catenin protein expression is up-regulated in ovarian carcinoma cells in serous effusions.

The aims of this study were firstly, to investigate the expression of E-cadherin complex proteins in ovarian carcinoma cells in serous effusions and in primary and metastatic lesions; and secondly to study the value of these four proteins and calretinin, a mesothelial marker, in the differential diagnosis of ovarian carcinoma cells from reactive mesothelial cells in effusions. Sixty-seven malignant effusions and 97 corresponding primary (n=36) and metastatic (n=61) lesions were immunohistochemically stained for E-cadherin and alpha-, beta-, and gamma-catenin. Staining extent and intensity were scored. Effusion specimens were additionally analysed for calretinin immunoreactivity. Membrane immunoreactivity for E-cadherin and alpha-, beta-, and gamma-catenin was detected on carcinoma cells in the majority of the effusions, but rarely on reactive mesothelial cells (p<0.001 for all markers). Calretinin immunoreactivity was confined to mesothelial cells (p<0.001). An association was seen between E-cadherin and alpha-catenin expression, in both effusions and solid tumours, and for beta-catenin in solid tumours (range p<0. 001 to p=0.014). Up-regulation of all four cadherin complex proteins was seen in carcinoma cells in effusions, when compared with corresponding primary tumours (range p<0.001 to p=0.028). As with effusions, metastatic lesions showed up-regulation of alpha-, beta-, and gamma-catenin when compared with primary carcinomas (p=0.002-0. 015). Carcinoma cells in effusions showed in addition elevated levels of E-cadherin when compared with metastatic lesions (p<0.001). Staining results in effusions showed no association with effusion site, tumour type or histological grade. Immunoblotting on 29 malignant effusions confirmed the presence of all four proteins in the majority of samples and co-precipitation of E-cadherin and beta-catenin was seen in ten specimens examined. E-cadherin complex proteins are widely expressed in ovarian carcinoma cells. Together with calretinin, they form a powerful battery of markers for the cytological diagnosis of carcinoma cells in effusions. The up-regulation of E-cadherin complex proteins in serous effusions and metastatic lesions may mark an early metastatic phenotype and possibly mediates survival of tumour cells at these sites through the inhibition of apoptosis.

Davidson B ，Berner A ，Nesland JM ，Risberg B ，Berner HS ，Tropè CG ，Kristensen GB ，Bryne M ，Ann Florenes V ... -  《JOURNAL OF PATHOLOGY》