Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinomain situ

Abstract

Loss of expression of the intercellular adhesion molecule E‐cadherin frequently occurs in invasive lobular breast carcinomas as a result of mutational inactivation. Expression patterns of E‐cadherin and the molecules comprising the cytoplasmic complex of adherens junctions, α‐, β‐ and γ‐catenin, were studied in a series of 38 lobular breast carcinomas with known E‐cadherin mutation status. The effect of loss of E‐cadherin by mutational inactivation (or other mechanisms) on the expression of catenins was investigated. Complete loss of plasma membrane‐associated E‐cadherin expression was observed in 32 out of 38 invasive lobular carcinomas, for which in 21 cases a mutation was found in the extracellular domain of E‐cadherin. In total, 15 frameshift mutations of small deletions or insertions, ranging from 1 to 41 bp, three non‐sense mutations, and three splice mutations were identified. Mutations were scattered over the whole coding region and no hot spots could be detected. In all cases, simultaneous loss of E‐cadherin and α‐ and β‐catenin expression was found; in 50 per cent of these cases, additional loss of γ‐catenin was observed. In six invasive lobular carcinomas, expression of both E‐cadherin and catenins was retained. In none of these carcinomas was an E‐cadherin mutation detected. Lobular carcinoma in situ adjacent to invasive lobular carcinoma showed simultaneous loss of E‐cadherin and catenins in all the cases studied—remarkably, also, in four cases positive for E‐cadherin and catenin expression in the invasive component. These results indicate that simultaneous loss of E‐cadherin and α‐, β‐ and γ‐catenin may be an important step in the formation of lobular carcinoma in situ, as a precursor of invasive lobular breast cancer. Events additional to E‐cadherin inactivation must be involved in the transition of lobular carcinoma in situ to invasive lobular carcinoma. © 1997 John Wiley & Sons, Ltd.

Invasive lobular carcinoma: to grade or not to grade

“…Other authors have found E-cadherin expression in 0-45% of invasive lobular carcinomas. [59][60][61][62][63][64][65][66][67][68] In these studies no correlation with grade was made. The discrepancy in the literature with regard to the percentage of invasive lobular carcinomas expressing E-cadherin may relate to differences between the populations studied, sensitivity and specificity of the antibodies used and diagnostic variation as applied to lobular carcinomas.…”

High expression levels of p27 correlate with lymph node status in a subset of advanced invasive breast carcinomas

“…For the evaluation of E-cadherin expression, we used previously published criteria. 31,49 The intensity of immunohistochemical staining in tumor cells was estimated semiquantitatively by comparison with normal pre-existing epithelial cells in the same section as an internal control. If the staining intensity of tumor cells was the same as that of normal epithelial cells, E-cadherin was considered as "preserved expression" (ϩϩ).…”

Atypical lobular hyperplasia and classic lobular carcinoma in situ in core biopsy specimens: routine excision is not necessary

“…Since their original description, variants of lobular carcinoma in situ have been recognized, aided by differential E-cadherin immunostaining. [3][4][5] These variants include pleomorphic lobular carcinoma in situ characterized by discohesive pleomorphic cells with abundant cytoplasm. 6 Rosen described 'florid' lobular carcinoma in situ characterized by 'tumor cells that fill and expand the duct lumen' that 'may develop central necrosis and calcifications'.…”