E-Cadherin, catenins and CD44 in breast carcinoma

Germline truncating mutations of E-cadherin predispose to familial breast carcinoma in association with hereditary diffuse gastric carcinoma³.

Reduced expression of E-cadherin is seen in about 50% of ductal carcinomas of the breast and is associated with high histological grade, nodal metastases and poor prognosis. One study shows E-cadherin status to be of particular prognostic significance within the node-positive group of patients². Most lobular carcinomas show complete loss of E-cadherin expression, frequently due to inactivating mutations.

Reference 1		CD44							E-cadherin	b-catenin
		s	v3	v4	v5	v6	v7	v9
normal		-	-	-	-	-	-	-	+++	+++
ductal hyperplasia		+/-	-	-	+	+	+	+/-	+++	+++
papilloma		+/-	-	-	+	+	+	+/-	+++	+++
adenosis		-	-	-	+	+	+	+/-	+++	+++
atypical ductal hyperplasia		+	+/-	+/-	+	+	-	+	+++	+++
ductal carcinoma in situ	not high grade	++	++	+/-	++	+++	-	+	+++	+++
	high grade	+	+	+	+	+	-	+	++	++
invasive ductal carcinoma	grade 1	+	++	-	+++	+++	+/-	++	+++	+++
	grade 2	+	+	+/-	+++	++	+	+	++	++
	grade 3	++	+	++	+++	++	+	++	+	++
lobular carcinoma in situ		+	+/-	+/-	++	+++	-	+	-	-
invasive lobular carcinoma		++	+/-	-	+++	++	+	+	+/-	+
correlates in invasive carcinoma		-	-	grade, tumour size, node status	grade	stage, oestrogen receptor status, disease-free survival	node status, progesterone receptor status	-	tumour size, node status, survival	node status, oestrogen receptor status

key

Another study concentrates on the pattern of staining:

Reference 4		E-cadherin	a-catenin	b-catenin	g-catenin	p120-catenin
Ductal carcinoma	grade 1	normal: 8 abnormal: 2	normal: 6 abnormal: 4	normal: 3 abnormal: 7	normal: 2 abnormal: 8	normal: 3 abnormal: 7
	grade 2	normal: 15 abnormal: 18	normal: 10 abnormal: 23	normal: 10 abnormal: 23	normal: 6 abnormal: 27	normal: 9 abnormal: 24
	grade 3	normal: 5 abnormal: 12 p = 0.01	normal: 2 abnormal: 15 p = 0.03	normal: 4 abnormal: 13	normal: 4 abnormal: 13	normal: 3 abnormal: 14
	total	normal: 28 negative: 8 cytoplasmic: 3 heterogeneous: 21	normal: 18 negative: 17 cytoplasmic: 4 heterogeneous: 21	normal: 16 negative: 3 cytoplasmic: 3 heterogeneous: 38	normal: 13 negative: 13 cytoplasmic: 4 heterogeneous: 40	normal: 15 negative: 7 cytoplasmic: 0 heterogeneous: 38
Lobular carcinoma		normal: 5 negative: 7 cytoplasmic: 6 heterogeneous: 2 p = 0.03	normal: 3 negative: 12 cytoplasmic: 0 heterogeneous: 5 p = 0.06	normal: 4 negative: 8 cytoplasmic: 0 heterogeneous: 8 p = 0.01	normal: 4 negative: 10 cytoplasmic: 2 heterogeneous: 4	normal: 7 negative: 1 cytoplasmic: 4 heterogeneous: 8

The normal pattern for E-cadherin, a-, b-, g- and p120-catenin is strong membranous staining with localisation at the intercellular borders of luminal cells⁴. Abnormal patterns are cytoplasmic, heterogeneous or lack of staining⁴. Abnormal expression of E-cadherin and catenins is more common in lobular than ductal carcinoma⁴, in particular complete absence of staining. Abnormal expression of E-cadherin and a-catenin expression appears not to be involved into the early stages of neoplasia but to correlate with high grade invasive ductal carcinoma. Abnormal expression of E-cadherin and b-catenin expression correlates with lymph node metastases⁴ while abnormal expression of a-catenin correlated with survival.

Diagnostic utility

• The combined e-cadherin and HMW cytokeratin immunoprofile may be useful in differentiating mammary intra-epithelial neoplasia into ductal, lobular and hybrid types.

References

Bankfalvi, A., Terpe, H. J., Breukelmann, D., Bier, B., Rempe, D., Pschadka, G., Krech, R., Lelle, R. J., Boecker, W. Immunophenotypic and prognostic analysis of E-cadherin and beta-catenin expression during breast carcinogenesis and tumour progression: a comparative study with CD44. Histopathology 1999;34:25-34.

²Elzagheid, A., Kuopio, T., Ilmen, M., Collan, Y. Prognostication of invasive ductal breast cancer by quantification of E- cadherin immunostaining: the methodology and clinical relevance. Histopathology 2002;41:127-133.

³Sobrinho-Simoes, M. and Oliveira, C. Different types of epithelial cadherin alterations play different roles in human carcinogenesis. Adv Anat Pathol 2002;9:329-37.

⁴Nakopoulou, L., Gakiopoulou-Givalou, H., Karayiannakis, A.J., Giannopoulou, I., Keramopoulos, A., Davaris, P. and Pignatelli, M. Abnormal alpha-catenin expression in invasive breast cancer correlates with poor patient survival. Histopathology 2002;40:536-46.

This page last revised 3.9.2001.

©SMUHT/PW Bishop