E-cadherin, CD44 and CD44v6 in squamous intraepithelial lesions and invasive carcinomas of the uterine cervix: an immunohistochemical study.
OBJECTIVE
To evaluate the immunoexpression pattern of E-cadherin, CD44std and the variant isoform v6 in normal squamous epithelium, low and high squamous intraepithelial lesions (SILs) and invasive squamous cell carcinomas (ISCCs) of the uterine cervix. The purpose was to determine whether any distinctive change in antigenic expression could contribute to the recognition of the earliest commitment to neoplasia and/or the onset of the invasive phenotype.


METHODS
Immunohistochemistry using the avidin-biotin indirect immunoperoxidase method was used to study the protein expression of epithelial cadherin (E-cadherin), cluster differentiation 44 (CD44), and the isoform v6 (CD44v6) in 124 human cervical samples (5 normal, 39 low-grade, 54 high-grade and 26 ISCCS) in formalin-fixed, paraffin-embedded tissue blocks.


RESULTS
Membranous expression of E-cadherin, CD44 and CD44v6 was preserved in normal squamous epithelium and in low-grade squamous intraepithelial lesions. A significant association was observed with the histological grade of the SILs and the immunoreactivity (membranous versus cytoplasmic) pattern of E-cadherin (p < 0.001), CD44std (p = 0.027) and CD44v6 (p < 0.001). A loss of membranous staining and a progressive increase in cytoplasmic staining was observed from low to high grade SILs to ISCCs.


CONCLUSIONS
Our study demonstrates that during the development of cervical lesions substantial qualitative (subcellular localization-membrane to cytoplasmic) and quantitative alterations (changes in expression) occur in the protein expression of E-cadherin, CD44, and CD44v6 in cervical cancer. The most striking observation was the decrease in membranous immunoreactivity and the progressive increase in cytoplasmic staining of E-cadherin, CD44 and CD44v6, relating to loss of differentiation as a consequence of neoplastic transformation.
Faleiro-Rodrigues
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Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portuguese Institute of Oncology of Francisco Gentil, Porto, Portugal. cristinafaleiro@mail.com
Lopes
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D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C112697:CD44v6 antigen; D015820:Cadherins; D006023:Glycoproteins; D018960:Hyaluronan Receptors