Prognostic Implication of Lymphovascular Invasion Detected by Double Immunostaining for D2-40 and MITF1 in Primary Cutaneous Melanoma

Abstract

Background: Lymphovascular invasion (LVI) is associated with adverse outcomes in primary cutaneous melanoma (PCM). Detection of LVI by hematoxylin and eosin staining alone is 0%-6%, but targeting lymphovascular structures increases the detection rate.Objective: To examine the prognostic significance of LVI detected by immunostaining for D2-40 and microphthalmia-associated transcription factor 1 (MITF1) in PCM. Methods:The authors retrospectively analyzed 120 PCM samples.We compared the LVI detection rates of immunostaining for D2-40 only (22%), double staining for D2-40 and MITF1 (38%), and hematoxylin and eosin, and examined the association of LVI with clinicopathologic variables and clinical outcomes.Results: Immunolabeling with both methods significantly increased the LVI detection rate. Double staining for D2-40 and MITF1 as well as D2-40-detected LVI was significantly associated with increased Breslow thickness, number of mitoses, and sentinel lymph node (SLN) metastasis. D2-40-detected LVI was also associated with ulceration. Although the difference was not significant, double staining for D2-40 and MITF1 allowed for easier detection of LVI than D2-40 alone.Limitations: This study was conducted in a tertiary referral institution; therefore, a referral bias cannot be excluded. Conclusions: Immunolabeling increased detection of LVI inPCM. Because LVI is a positive predictive marker for SLN metastasis, the authors propose using anti-D2-40 and anti-MITF1 in the evaluation of LVI in patients with PCM with a certain risk of SLN metastasis.

Lymphatic invasion predicts sentinel lymph node metastasis and adverse outcome in primary cutaneous melanoma

“…Despite observing no association between LI within melanomas and SLN status, Rose et al showed a significant association between LI and disease‐free and overall survival in a multivariate analysis. In another study, there was no significant association with LI and clinical outcome, including lymph node metastasis, distant metastasis and survival . Xu et al found a significant association between LI and time to metastasis and melanoma‐specific death.…”

“…In both univariate and multivariate analyses, Fohn et al showed that LI is the best predictor of SLN status when compared to mitotic rate, tumor thickness, presence of ulceration, patient age and patient gender. Feldmeyer et al also demonstrated that the detection of LI using dual immunohistochemistry is associated with SLN metastasis. In a study of "melanocytic tumors of uncertain malignant potential," Abraham et al showed that LI as detected by dual immunohistochemistry for D240 and S100 was associated with nodal metastasis and melanoma‐related death, suggesting that identifying LI in ambiguous melanocytic tumors may help predict tumors capable of metastasis.…”

“…Most recently, Feldmeyer et al used dual staining with D240 and MiTF immunohistochemistry for melanomas without detectable LI on H&E stained sections, and detected LI in 38% of cases. It remains to be determined whether there is an optimal melanocytic marker for this purpose.…”

Lymphatic invasion and angiotropism in primary cutaneous melanoma

“…Despite these findings, a number of additional studies showed no association between the detection of lymphatic invasion in primary melanomas and survival (Table 1). 19,25,31 Egger et al 12 detected a significant difference in OS only by univariate analysis but showed that lymphatic invasion was associated with a worse OS in patients with regression. Interestingly, in a study of 116 melanomas with regression, Yun et al 40 found that patients with lymphatic invasion in areas of complete regression had a shorter time to first metastasis and melanoma-specific death than those who did not have lymphatic invasion, suggesting that the adverse prognostic effect of regression may be in part mediated by lymphatic invasion.…”

Angiogenesis in melanoma: an update with a focus on current targeted therapies

“…Compared with H&E staining and/or immunohistochemical staining with a single vascular marker, double immunohistochemical staining with both a melanocytic and vascular marker (eg, S100+D2-40, MITF+D2-40, SOX-10+D2-40) has been reported to be more sensitive and specific for the detection of lymphovascular invasion in melanoma 54 55…”