Glycoprotein CD44 Expression in Human Breast Cancer: An Immunohistochemical Study Including Correlation with Cathepsin D, Type IV Collagen, Laminin, Fibronectin, EGFR, c-erbB-2 Oncoprotein, p53, Steroid Receptor Status, and Proliferative Indices

Abstract

CD44, an integral membrane glycoprotein has diverse functions in cell-cell and cell-matrix interactions and may be a determinant of metastatic and invasive behavior in carcinomas. The expression of CD44 in 86 female breast carcinomas was examined by immunohistochemistty using the monoclonal mouse antihuman phagocytic glycoprotein-1, CD44 (clone DF 1485) on formalin-fixed, paraffin-embedded tissue. The CD44 expression was studied in correlation with the expression of basement membrane (BM) antigen (type IV collagen, laminin), fibronectin, cathepsin D, p53, c-erbB-2, proliferative activity Ki-67, PCNA), steroid receptor content, as well as with other conventional clinicopathological parameters in breast cancer. CD44 expression was observed in variable amounts in the epithelial cells of the control group (cases of fibrocystic and benign proliferative-breast disease). CD44 expression showed a heterogeneous pattern, such as small foci amounting t o less than 5% of the total cells in a given section, or larger clusters of tumor cells weakly or strongly stained. A greater proportion of the tumor stained in a patchy pattern. Seventy-two point six percent of tumors showed CD44 expression (>5% of neoplastic cells). In 10.9% of the cancer, more than 90% of the cancer cells stained positively for CD44. High values of CD44 were correlated with lymphnode involvement (p = 0.006) and progesterone receptor content (p = 0.02). There was no significant correlation between CD44 expression and the other clinicopathological parameters, including tumor size, age of patient, histological type, tumor grade and estrogen receptor content as well as with the other prognostic parameters.These findings suggest that the CD44 expression in breast cancer is independent of the expression of extracellular components, the proteolytic enzyme cathepsin D, and the growth fraction of tumor, but may be useful for monitoring human-breast metastasis.D44 is a cell surface receptor for hyaluronate sug-C gesting a role in the regulation of cell and cell-substrate interactions as well as cell migration ( 1 ) . The

Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck

“…In accordance with this finding, nuclear accumulation of p53 that was detected immunohistochemically was associated strongly with up‐regulation of MMP expression and basement membrane degradation in urothelial carcinomas 38. Similarly, a positive correlation was found between p53 and MMP‐3 expression in breast carcinoma 39. Taken together, these results strongly suggest that MMP expression may be up‐regulated in tumor progression as a result of p53 inactivation.…”

Prognostic evaluation of metallothionein expression in human colorectal neoplasms.

“…Thus we assumed that CD44 expression may be involved in the process of invasion and metastasis, probably with the cooperation of cathepsin D, and its expression could be an indicator of poor prognosis in colorectal adenocarcinomas. 31 In addition, the inverse correlation between metallothionein and CD44 expression would support the view that in colorectal cancer the metallothionein expression is associated with a favourable outcome. 22 This would tend to confirm the diVerent biological role of metallothionein expression in colorectal cancer, possibly because in colorectal tissue there is considerable inflammatory infiltrate and this could induce metallothionein synthesis through interferon production by activated T lymphocytes.…”

β‐Catenin and p53 analyses of a breast carcinoma tissue microarray

“…In less well established markers (e.g., EGFR, Met, p53, ␤-catenin, cyclin D1, and MMP7), breakpoints that were most consistent with the literature were used. 22,25,26 Descriptions in the literature of ␤-catenin expression patterns in breast carcinoma especially have been limited and inconsistent. 27,28 Our laboratory and others have seen ␤-catenin nuclear staining in many tumor types.…”