Is E-cadherin/catenin axis important in grade III ductal carcinomas?
- George Skliris1
© Biomed Central Ltd 2001
Received: 17 May 2001
Accepted: 20 August 2001
Published: 1 December 2001
Cadherins are glycoproteins, mainly expressed in epithelial cells, that mediate cell-cell adhesion and interact with the interior of the cell via intracellular proteins called catenins. Through interaction with a-actin, a-catenin influences cell motility. ?- and ?-catenins compete with each other for cadherin-binding sites, and the genes encoding them have been proposed as an oncogene and a tumour suppressor gene respectively. Not much is known regarding E-cadherin and catenin expression in breast cancer. Although some studies have linked reduced E-cadherin expression with poor outcome, others have revealed no independent prognostic value. Recent research has found that retained membrane E-cadherin expression was surprisingly associated with shorter survival in a study employing grade I ductal tumours (see Additional information). This study investigated E-cadherin and a-, ?- and ?-catenin protein levels in a cohort of 470 patients diagnosed with grade III ductal carcinomas.
E-cadherin was detected through membrane staining in 294 cases (62%) and in cytoplasmic staining in 169 cases (36%). Membrane expression of a-catenin was present in 419 cases (91%), while 382 cases (83%) showed cytoplamsic staining. Membrane expression of ?- and ?-catenin was found in 362 cases (78%) and in 354 cases (77%) respectively, while cytoplasmic expression was detected in 284 cases (61%) and in 314 cases (68%) respectively. A notable association between membrane expression of E-cadherin and all the catenins was found, while presence of all the catenins shows an association with each other. Strong membrane and cytoplasmic E-cadherin and a-catenin expression was associated with positive oestrogen receptor (ER) status. Interestingly, patients with strong membrane expression of E-cadherin, a- and ?-catenin had significantly shorter relapse-free and overall survival rates.
Membrane expression of E-cadherin and a- and ?-catenin in grade III ductal carcinomas was associated with aggressive disease. Loss of E-cadherin function - believed to contribute to increased proliferation, invasion and metastasis - is well documented in lobular breast cancers. However, loss of heterozygosity within 16q, where the E-cadherin gene lies, is infrequent in grade III ductal carcinomas, so it was quite surprising that membrane staining was absent in 38% of the examined carcinomas. As no dyscohesion was detected, it was suggested that P-cadherin might be responsible for cohesion in some of these tumours. Future studies should investigate the role of E-cadherin and catenin expression in other ductal grades and histological carcinoma types.
Tan DS, Potts HW, Leong AC, Gillett CE, Skilton D, Harris WH, Liebmann RD, Hanby AM: The biological and prognostic significance of cell polarity and E-cadherin in grade I infiltrating ductal carcinoma of the breast. J Pathol 1999, 189:20-27 (PubMed abstract).