CD24 is highly useful in differentiating high-grade serous carcinoma from benign and malignant mesothelial cells

Summary

CD24 was previously shown to be overexpressed in high-grade serous carcinoma (HGSC) effusions compared to malignant mesothelioma (MM) in gene expression array analysis. The present study validated this observation in a large series consisting of both effusions and surgical specimens. Effusions (n = 206; 100 HGSC, 16 ovarian carcinomas of other histological types, 54 breast carcinomas, 36 MM) and surgical specimens (n = 182; 117 ovarian carcinomas, 65 MM) were analyzed for CD24 expression using immunohistochemistry. CD24 was expressed in 105/116 (91%) ovarian carcinoma and 16/54 (30%) breast carcinoma effusions, while it was uniformly absent in MM (0/36; 0%; P < .001). Reactive mesothelial cells were CD24-negative in all carcinoma specimens. Comparative analysis of 117 solid primary (n = 43) and metastatic (n = 74) ovarian carcinomas and 65 solid MM specimens showed CD24 expression in 46% (54/117) of the former compared to 3% (2/65) of the latter (P < .001). Comparative analysis of ovarian carcinomas at different anatomic sites showed significantly higher CD24 expression in effusions compared to solid ovarian and metastatic lesions (P < .001), with similar results when analysis was limited to HGSC (P < .001). In conclusion, CD24 is a highly sensitive and specific marker of ovarian carcinoma in the differential diagnosis from MM and reactive mesothelium in effusions. CD24 is similarly a specific marker in surgical specimens, though with lower sensitivity. The overexpression of CD24 in ovarian carcinoma effusions compared to solid lesions may be due to the acquisition of cancer stem cell characteristics.

Introduction

Ovarian cancer, consisting predominantly of ovarian carcinoma (OC), is the most lethal gynecological cancer. Efforts directed at improving the outcome of OC patients have been checked by the absence of a robust test for early detection, as well as by chemoresistance that develops in the majority of patients after repeated cycles of chemotherapy. Targeted therapy has to date shown only modest effect in changing this bleak picture [1], [2].

It is widely recognized that small tumor cell populations escape death by chemotherapy and constitute the cellular niche from which recurrence develops in many cancers. The term cancer stem cells (CSC) has been used by some investigators to describe these cells and different markers, including ALDH1A1, CD44, CD117 (c-Kit), CD133 and EpCAM, have been proposed as putative CSC markers in OC (reviewed by Jaggupili et al, Burgos-Ojeda et al, Garson et al [3], [4], [5]).

While the validity of the above-mentioned proteins as CSC markers has been questioned, the case is still more ambiguous for CD24, a cell surface glycoprotein mediating tumor cell adhesion to P-selectin expressed on endothelial cells and platelets, and thus postulated to promote metastasis [5]. CD24 has been described as both positive and negative CSC marker, partly depending on tumor origin, but also in OC itself [3].

Immunohistochemistry (IHC) is the most widely used ancillary method in both cytopathology and surgical pathology, and panels which aid in the detection and classification of cancers involving the serosal cavities have been constantly expanding and improving in recent years. The differential diagnosis between serous carcinoma of female genital origin and malignant mesothelioma (MM) is nevertheless difficult in some cases owing to the overlapping morphology and immunomarker expression of these tumors. The majority of antibodies are not 100% sensitive or specific, and the use of several markers is therefore mandated [6].

CD24 was previously identified by our group as a specific marker of ovarian/peritoneal serous carcinoma in the differential diagnosis from diffuse malignant peritoneal mesothelioma (DMPM) using gene expression analysis applied to effusion specimens [7]. Results were not validated at the protein level in the original study, nor has this observation been followed by other investigators to the best of the author's knowledge. The present study analyzed the diagnostic role of CD24 in differentiating OC, primarily high-grade serous carcinoma (HGSC), from MM.