E-cadherin: a differentiation marker in thyroid malignancies.
Loss of E-cadherin (uvomorulin), a Ca(2+)-dependent cell adhesion molecule required for normal epithelial function, has been attributed a pathogenetic role in tumor invasion. The expression of E-cadherin was studied in normal and neoplastic follicular epithelium of the human thyroid by Northern blot analysis and immunofluorescence on frozen tissue sections. In the normal thyroid (n = 10) and in benign thyroid disorders (n = 21; toxic diffuse goitre; multinodular goitre; follicular adenomas), E-cadherin mRNA levels were equally high and the follicles were generally stained, mainly along the lateral surface of the epithelial cells, by the anti-E-cadherin monoclonal antibody. In anaplastic thyroid carcinomas (n = 6) E-cadherin expression was very low or lacking. In papillary carcinomas (n = 23), E-cadherin mRNA levels varied from nearly normal to highly reduced, which roughly correlated with the overall immunofluorescence intensity. However, the immunostaining also revealed a heterogeneous "all-or-nothing" expression of E-cadherin among adjacent cells in the same tumor. In the follicular carcinomas (n = 9), E-cadherin mRNA levels were in general rather high but the immunostaining varied considerably. A few papillary and follicular tumors lacked immunoreactive E-cadherin in spite of high mRNA levels. In oxyphilic (Hürthle) cell tumors, comprising both adenomas (n = 4) and carcinomas (n = 2), E-cadherin immunoreactivity was reduced and distributed intracellularly rather than at the cell surface. The expression of E-cadherin in relapsing thyroid carcinomas and in tumors with metastatic spreading was, irrespective of the histiotype, low or lacking. Sequential Northern analysis revealed a close correlation between the expression levels of E-cadherin and the thyrotropin receptor. Together, the data suggest that in human thyroid malignancies both gene expression and posttranscriptional control of E-cadherin may be impaired.
Brabant
G
G
Department of Clinical Endocrinology, Medizinische Hochschule, Hannover, Germany.
Hoang-Vu
C
C
Cetin
Y
Y
Dralle
H
H
Scheumann
G
G
Mölne
J
J
Hansson
G
G
Jansson
S
S
Ericson
L E
LE
Nilsson
M
M
D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015152:Blotting, Northern; D015820:Cadherins / Q000032:analysis* / Q000096:biosynthesis*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D005455:Fluorescent Antibody Technique; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000096:biosynthesis; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D015820:Cadherins; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin