CD44 Expression Is Associated with Increased Survival in Node-Negative Invasive Breast Carcinoma

Abstract

Purpose: CD44 is a multifunctional cell surface receptor with many known splice variants, some of which have been reported to play a role in tumor progression. The purpose of this study was to evaluate the prognostic significance of CD44 isoforms in early-stage, lymph node^negative invasive breast carcinoma. Experimental Design: Immunohistochemical staining for CD44 isoforms was done on archival paraffin tissue sections of invasive breast carcinoma from a cohort of lymph node^negative patients who received no adjuvant tamoxifen or chemotherapy and who had a mean clinical follow-up period of 15 years. Immunohistochemical staining was done with antibodies to CD44s, the standard isoform of CD44, and to isoforms containing variant exon 6 (CD44v6); levels of staining were correlated with clinical outcome data.Results: There was a trend towards increased disease-free survival for patients whose tumors had high anti-CD44s positivity (P = 0.05), and a significant association was observed between anti-CD44s positivity and disease-related survival (P = 0.04). Expression of CD44v6 isoforms did not correlate with clinical outcome. Conclusion: CD44 expression, as assessed by immunohistochemical staining with anti-CD44s, may be a favorable prognostic factor in patients with node-negative invasive breast carcinoma.

A self‐enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells

“…37 However, in melanoma and other cancer types CD44s was involved in tumor suppression. 23,44,45 Although several variant isoforms are blocking an invasive phenotype, [46][47][48] an opposing role of specific CD44v isoforms have been found to support tumor growth and malignancies (reviewed in Ref. 23).…”

The Hyaluronan Receptors CD44 and Rhamm (CD168) Form Complexes with ERK1,2 That Sustain High Basal Motility in Breast Cancer Cells

“…These experimental discrepancies, which reveal the capacity of CD44 to both promote and inhibit motility and invasion, mirror the dual relationship of CD44 expression to clinical outcome of breast cancer patients. In breast cancers, overexpression of the standard or specific variant forms has not consistently been demonstrated to relate to outcome parameters (25,28,29,87). One conclusion from these studies is that it is CD44 variant forms, which are expressed at different stages of breast tumor progression (13,27), that perform distinct functions from CD44std in tumor progression.…”

CD44 is overexpressed in basal-like breast cancers but is not a driver of 11p13 amplification

“…With respect to patient outcome, again a consistent trend has failed to emerge. For example, it has been reported that there is a significant correlation between CD44s expression and increased disease-free survival in nodenegative patients [8] and that expression of CD44v7-8 correlates with decreased overall survival [6]. Similarly it has been reported both that CD44v6 is and is not a poor prognostic marker [6,9].…”

“…The proportion of tumours showing positive staining was scored as follows: 0 (0%), 1 (\1%), 2 (1-10%), 3 (11-33%), 4 (34-66%), 5 (67-100%). Intensity and proportion of staining were added and cases classified as negative (0-2), low expression (3-5) and high expression (6)(7)(8). CD44 immunohistochemical analysis was performed by two observers (CM & JRF) blinded to the results of other immunohistochemical markers, CD44 CISH and patients' outcome.…”

“…Excessive alternative splicing and posttranslational modifications give rise to a family of transmembrane glycoproteins with diverse structural and functional properties. The standard CD44 isoform (CD44s) contains none of the alternatively spliced exons (variant exons [1][2][3][4][5][6][7][8][9][10] and is expressed by nearly all cell types. In contrast, the alternatively spliced, variant isoforms (CD44v) show a highly restricted expression pattern during embryonic development, in pathological backgrounds or in a cell type specific manner, for example, epithelial cells mainly express CD44v8-v10.…”