Expression of milk fat globule epidermal growth factor-VIII may be an indicator of poor prognosis in malignant melanoma.

Milk fat globule epidermal growth factor-VIII (MFG-E8) is a secreted protein that binds phosphatidylserine and promotes apoptotic cell ingestion by phagocytes, mediating the immune tolerance and maintenance of homeostasis. A recent study has shown that MFG-E8 expression in human melanoma is increased with tumour progression; however, the effect of its expression on patient survival has not yet been clarified. To analyse MFG-E8 expression in melanoma, and to determine whether it can serve as a marker for diagnosis, tumour progression and/or prognosis. MFG-E8 expression was examined by immunohistochemistry in 60 primary melanomas, 22 metastatic lesions and 30 benign naevi. The following clinicopathological variables were evaluated: age, gender, histological type, tumour site, Breslow thickness, Clark's level, the presence or absence of ulceration and tumour-infiltrating lymphocytes, and survival periods. Statistical analyses were performed to assess associations and melanoma-specific survival. MFG-E8 expression was significantly higher in primary and metastatic melanoma than in naevus. Furthermore, it increased according to tumour progression and metastasis. Patients with MFG-E8 expression in primary tumours had significantly shorter survival periods than those without MFG-E8 expression. Univariate and multivariate analyses revealed that MFG-E8 expression was a statistically significant and independent prognostic factor. MFG-E8 expression may serve as a tumour progression marker and can predict an unfavourable prognosis in patients with melanoma.

Oba J ，Moroi Y ，Nakahara T ，Abe T ，Hagihara A ，Furue M ... -  《-》

Expression of CD10 predicts tumor progression and unfavorable prognosis in malignant melanoma.

CD10 expression in malignant melanoma (MM) has been reported to increase according to tumor progression and metastasis; however, its association with patient outcome has not been clarified. We examined the immunohistochemical expression of CD10 in MM to determine whether or not it could serve as a marker for tumor progression and prognosis. A total of 64 formalin-fixed, paraffin-embedded samples of primary MM were immunostained for CD10. Similarly, 40 samples of melanocytic nevus and 20 of metastatic MM were analyzed for comparison. The following clinicopathologic variables were evaluated: age, gender, histologic type, tumor site, Breslow thickness, Clark level, the presence or absence of ulceration and tumor-infiltrating lymphocytes, and survival. Statistical analyses were performed to assess for associations. Several parameters were analyzed for survival using the Kaplan-Meier method and Cox proportional hazards model. Immunohistochemical analysis revealed that 34 of 64 cases (53%) of primary MM expressed CD10, compared with 15 of 20 cases (75%) of metastatic MM and only 4 of 40 cases (10%) of nevus. There was a significant positive relationship between CD10 expression and Breslow thickness, Clark level, and ulceration. Univariate analysis revealed 4 significant factors for shorter survival periods: CD10 expression, high Breslow thickness, high Clark level, and the presence of ulceration (P < .01 each). In multivariate analysis, CD10 expression was revealed to be a statistically significant and independent prognostic factor. The major limitation was the small sample size. CD10 expression may serve as a progression marker and can predict unfavorable prognosis in patients with MM.

Oba J ，Nakahara T ，Hayashida S ，Kido M ，Xie L ，Takahara M ，Uchi H ，Miyazaki S ，Abe T ，Hagihara A ，Moroi Y ，Furue M ... -  《-》

Expression of milk fat globule EGF-factor 8 (MFG-E8) mRNA and protein in the human endometrium and its regulation by prolactin.

Franchi A ，Bocca S ，Anderson S ，Riggs R ，Oehninger S ... -  《-》

Epithelial cell protein milk fat globule-epidermal growth factor 8 and human chorionic gonadotropin regulate stromal cell apoptosis in the human endometrium.

To study the regulation of apoptosis in human endometrial cells. The specific aims were to determine whether milk fat globule-epidermal growth factor 8 (MFG-E8), a novel endometrial epithelial protein, modulates caspase activation and DNA fragmentation; and to examine whether hCG, an early embryonic product, regulates Bax and Bcl-2 equilibrium, as well as MFG-E8 expression. Primary cultures of human endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). Academic center. Ovulatory women aged 21-30 years. Treatment with MFG-E8 and hCG. Apoptotic activity was quantified using a luciferase assay. Deoxyribonucleic acid fragmentation was detected by TUNEL assay. Bax, Bcl-2, and MFG-E8 messenger RNA expression levels were determined by quantitative reverse transcription-polymerase chain reaction. Immunocytochemistry was used to establish cell purity and presence of MFG-E8 and hCG-R (receptor) proteins. Endometrial epithelial cells were cytokeratin(+), vimentin(-), MFG-E8(+), and hCG-R(+), whereas ESC were vimentin(+), cytokeratin(-), MFG-E8(-), and hCG-R(+). Treatment of ESC with MFG-E8 resulted in a 13-fold increase in caspase activity and a 30-fold increase in TUNEL. On the other hand, hCG decreased messenger RNA expression of Bax in ESC. Milk fat globule-epidermal growth factor 8 has proapoptotic activity, suggesting participation in endometrial remodeling via an epithelial-stromal cell paracrine effect. Conversely, pregnancy levels of hCG has opposite effects on stromal cells.

Riggs RM ，Bocca S ，Anderson S ，Franchi A ，Rhavi BS ，Oehninger S ... -  《-》

Dendritic cell-derived exosomes containing milk fat globule epidermal growth factor-factor VIII attenuate proinflammatory responses in sepsis.

Miksa M ，Wu R ，Dong W ，Das P ，Yang D ，Wang P ... -  《SHOCK》