CD44 expression in benign and malignant nevomelanocytic lesions.

CD44 is an integral membrane glycoprotein that is a principal receptor for hyaluronan and plays a role in cell-extracellular matrix interactions. Recent studies of melanomas in mouse models have suggested that increased CD44 expression by these tumors may relate to metastatic potential. Immunohistochemical expression of CD44 (standard [s] and variant [v6]) in benign and malignant nevomelanocytic lesions was assessed in formalin-fixed, paraffin-embedded tissue and was correlated with histological parameters and prognostic factors. Cases included benign nevi (three junctional, four compound, five intradermal, five blue, six Spitz, one deep penetrating), architecturally disordered (dysplastic) nevi (three, and primary (22) and metastatic melanomas (eight). All of the benign lesions showed diffuse and essentially uniform membrane staining of CD44s in nevomelanocytic cells, regardless of lesion size, depth, or extent of dermal involvement. In contrast, semiquantitative analysis (0 to 3+) of the primary melanomas showed heterogeneous and decreased staining of CD44s, which inversely correlated with lesion size (-0.569) and depth of invasion (-0.622 and -0.617 for Breslow's depth and Clark's level, respectively). These results were significant at P < .05. CD44s expression in metastases paralleled that of their respective primaries. None of the benign nevomelanocytic lesions showed CD44v6 staining. In contrast, all of the malignant nevomelanocytic lesions showed cytoplasmic staining of the tumor cells. Pretreatment with chondroitinase did not alter CD44s staining. CD44s expression by immunohistochemical determination is uniform in benign nevomelanocytic lesions. Malignant melanomas show decreased, heterogeneous staining that inversely correlates with increasing size, depth, and level of invasion. CD44 expression may be a prognostic indicator in malignant melanomas. Tumor staining with anti-chondroitin sulfate monoclonal antibodies suggests that CD44s may be expressed as a chondroitin sulfate proteoglycan in primary melanomas.

Expression of CD44 isoforms in human prostate tumor cell lines.

We have examined the expression of the transmembrane glycoproteins CD44 in four human prostate tumor cell lines. Expression was examined at the protein level by flow cytometric analysis and Western blot, and at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR). All four cell lines (DU145, LNCaP, PC3, and ND1) expressed the standard CD44 isoform (CD44s) at the mRNA level and all cell lines except LNCaP expressed CD44s at the protein level. All four cell lines contained one or more isoforms containing the v6 region (exon 10) at the mRNA level, which has been associated with metastatic potential. However, a subpopulation of LNCaP and ND1 cells showed protein expression of v6. In addition, soluble CD44 isoforms were identified in cultured supernatants from all cell lines except LNCaP. These results show that CD44 isoforms are expressed on human prostate tumor cell lines, including the expression of variant isoforms containing the v6 region, and provide a rationale for the further study of this cellular adhesion molecule in prostate cancer. In addition, preliminary results indicate altered expression of CD44 in human prostatic adenocarcinomas examined immunohistochemically.

The expression of epidermal growth factor receptor and transforming growth factor alpha in renal cell carcinoma.

Immunohistochemical stains using antibody to epidermal growth factor receptor (EGFR) and transforming growth factor alpha (TGF-alpha) were applied to 67 cases of renal cell carcinoma retrieved from the files of the Division of Surgical Pathology. The 64 patients (33 females, 31 males) ranged in age from 35 to 87 years (mean, 61 years). Two patients had more than one renal carcinoma included in this study. Fifty-seven cases (85%) expressed EGFR, with staining largely confined to the cell membrane. Staining intensity was directly correlated with tumor grade (P = 0.02, T test), size (P = 0.04), and stage (P = 0.01). Those cases with more intense EGFR staining also appear to have shorter patient survival than those showing less intense staining (43 mo versus 63 mo, P = 0.05). Forty-nine cases (73%) expressed TGF-alpha in a distribution similar to that of EGFR. There was no significant correlation between TGF-alpha staining intensity and tumor size, stage, or grade. When the tumor expressed either EGFR or TGF-alpha but not both proteins, average patient survival was 38 months, while the average survival of those patients whose tumors expressed both EGFR and TGF-alpha was 61 months (P = 0.04). Three of eleven cases, all of which expressed EGFR, were felt to show EGFR gene amplification using a modification of the differential polymerase chain reaction on archival, formalin-fixed, paraffin-embedded tissue. EGFR and TGF-alpha likely play a role in the progression of renal cell carcinoma, and their coexpression may have favorable prognostic implications.