E-Cadherin, CD44 and CD44v6 in Squamous Intraepithelial Lesions and Invasive Carcinomas of the Uterine Cervix: An Immunohistochemical Study

Abstract

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.

Abnormal Immunoexpression of Cell Adhesion Molecules (CAMs) in Cervical Cancer

“…30,[34][35][36] It is worth insisting that different results from diverse studies may be a result of variations of technical types (different antigenic retrieval methods and specificity of the primary antibodies used) as well as the consideration of different parameters for the interpretation of the immunohistochemical results. 14 In conclusion, our findings confirm that in cervical cancer, the cellular interaction is found to be markedly altered by loss or decrease of the membrane antigenic expression and by predominantly cytoplasmic localization when compared with benign epithelial cervical tissue. These findings reaffirm that the loss of cell cohesiveness occurs in the malignant phenotype.…”

“…3 The loss or alteration in cellular adherence is also characteristic of squamous and glandular cervical cancer as well as their respective precursor lesions. [12][13][14][15][16] During the development of cervical lesions, alterations essential in CAM expression occur, which are either qualitative in character (cytoplasmic or membrane localization) or quantitative (changes in expression). 11,14,17 The abnormal expression of E-cadherin in cervical cancer could be one of the factors responsible for the invasion and metastasis of this neoplasm.…”

Downregulation of BRG-1 repressed expression of CD44s in cervical neuroendocrine carcinoma and adenocarcinoma

“…[39][40][41]43 In our study, the expression rates of CD44s are statistically higher in squamous cell carcinomas, as compared to adenocarcinomas and neuroendocrine carcinomas, but different results exist. 39,41 The CD44s expression rates in our squamous cell carcinoma cases are slightly higher than that of the Faleiro-Rodrigues' series, 41 but our adenocarcinoma cases have CD44s expression rates lower than that of Lu's series. 39 In Saegusa's series, the average immunoreactivity scores for CD44s were significantly higher in squamous cell carcinoma cases than in adenocarcinoma cases, a result which is similar to ours.…”

“…[32][33][34][35][36][37][38] The neuroendocrine carcinoma mentioned here refers to small cell carcinoma and large cell neuroendocrine carcinoma. Although expression of CD44s and its isoforms in cervical lesions has been reported by several sources, [39][40][41] the total case number is limited and no published paper discusses the expression of CD44 isoforms in cervical neuroendocrine tumors or the different expression rates of major cancer types. In contrast, loss of CD44s in nearly all cases of small cell lung cancer has been reported, and different expression rates are noted between small cell lung cancer and non-small cell carcinoma.…”

Chemoradiation-induced expression of fibroblast growth factor-2 and laminin in patients with cervical cancer

“…[7][8][9][10][11][12][13][14][15] We showed previously by microarray analysis that CRT activates signaling from the extracellular matrix (ECM), and revealed many CRT-responsive genes in pre-and mid-radiotherapy cervical cancer biopsies. 16 These genes included basic fibroblast growth factor-2 (FGF2) and heparanase (HPSE).…”