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 ... -  《-》

Clinicopathologic and prognostic significance of SATB1 in cutaneous malignant melanoma.

Special AT-rich sequence-binding protein-1 (SATB1), a new type of gene regulator, has been reported to be expressed in several human cancers and may have malignant potential. However, no data on SATB1 expression and its relationship to tumor progression in cutaneous malignant melanoma (CMM) has yet been reported. We examined the immunohistochemical expression of SATB1 in CMM to determine whether it could serve as a prognostic marker. A total of 97 samples of primary CMM and controls were immunostained for SATB1. The following clinicopathologic variables were evaluated: age, gender, subtype, SATB1 expression, Breslow thickness, Clark level, presence of ulceration, lymph node metastasis, distant metastasis, 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. Forty cases (85.1%) of CMM showed positive staining for SATB1 by immunohistochemistry. The intensity of SATB1 staining was significantly higher in CMM than in nevus NV and normal skin (NS) (P < 0.01). High SATB1 expression was significantly correlated with Breslow thickness, Clark level, mortality, presence of ulceration, and lymph node metastasis (P < 0.01). Moreover, Kaplan-Meier analysis revealed that SATB1 overexpression was significantly associated with worse survival (P < 0.01). Further univariate analysis and multivariate regression analysis indicated that SATB1 expression was an independent prognostic marker for CMM (P = 0.03). The overexpression of SATB1 correlated with metastatic potential of CMM and is a novel independent prognostic marker for predicting outcome.

Chen H ，Takahara M ，Oba J ，Xie L ，Chiba T ，Takeuchi S ，Tu Y ，Nakahara T ，Uchi H ，Moroi Y ，Furue M ... -  《-》

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 ... -  《-》

Regression does not predict nodal metastasis or survival in patients with cutaneous melanoma.

Burton AL ，Gilbert J ，Farmer RW ，Stromberg AJ ，Hagendoorn L ，Ross MI ，Martin RC 2nd ，McMasters KM ，Scoggins CR ，Callender GG ... -  《-》

Identification of higher risk thin melanomas should be based on Breslow depth not Clark level IV.

There is good prognostic correlation for the two microstaging systems, Breslow depth and Clark level, commonly used to stage melanomas. Many investigators have reported that Breslow depth is the superior microstaging method. Although Clark level has been dropped from most of the proposed American Joint Committee on Cancer (AJCC) melanoma staging system, the AJCC system still includes Clark Level IV as a criterion for upstaging thin melanomas. The authors sought to determine whether this is appropriate, based on melanoma patient data in the Duke Comprehensive Cancer Center database. Of the 8833 patients registered between January 1, 1970 and December 31, 1995, complete data on Breslow depth and Clark level was available for 4560 patients who were without nodal or metastatic disease at presentation. Ten-year survival was measured from the date of excision of the primary tumor until death from melanoma and analyzed using Kaplan-Meier and Cox proportional hazard methodologies. When analyzed separately, both increased Breslow thickness and Clark level correlated with shorter survival times. During subgroup analysis, Breslow thickness remained a significant prognostic indicator of survival at Clark Levels III and IV. Conversely, at narrow levels of Breslow thickness (i.e., 0-0.75 mm, > 0.75 -1.0 mm, > 1.0-1.5 mm) survival times were indistinguishable between Clark Levels III and IV. For the broader Breslow thickness interval of 0-1.0 mm, a barely significant difference between Clark Levels III and IV could be obtained. However, for this thickness range, even greater differences in survival could be obtained by merely comparing Breslow subgroups (i.e., < or = 0.8 mm vs. > 0.8-1.0 mm, < or = 0.9 mm vs. > 0.9-1.0 mm). The authors' data suggested that, after controlling for Breslow depth, Clark level was not a good prognostic indicator for survival. If the AJCC's objective is to design a classification system that will reliably predict the higher risk melanomas, then the system should be based on tumor thickness, which is clearly a better prognostic indicator, and should not be modified because of Clark level.

Owen SA ，Sanders LL ，Edwards LJ ，Seigler HF ，Tyler DS ，Grichnik JM ... -  《-》