Immunohistochemical Studies of Conjunctival Nevi and Melanomas

Abstract

To evaluate the role of immunohistochemical methods in the diagnosis of benign and malignant conjunctival melanocytic proliferations.Design: Retrospective immunohistopathologic study.Methods: Paraffin-embedded tissue sections from 20 conjunctival nevi and 15 invasive melanomas were immunoreacted with antibodies against cellular antigens S-100 protein, MART-1, HMB-45, CD-45, and Ki-67 nuclear proliferation protein.Results: All nevi immunostained moderately to strongly for S-100 protein and MART-1. Results for HMB-45 were negative in the middle and lower subepithelial portions of 18 of 20 lesions; it was usually only weakly positive within the superficial junctional zone. Only 1 melanoma did not stain positively for S-100; MART-1 and HMB-45 were positive in all lesions at some level of intensity. Ki-67 positivity was restricted to the junctional zone of nevi and was diffuse in melanomas. The mean Ki-67 proliferation indices were 1.89% for the nevi and 17.3% for the melanomas. CD-45 can help to highlight lymphocytes that immunostain with Ki-67. Melanomas in situ and atypical primary acquired melanoses had more than twice the Ki-67 proliferation counts of intraepithelial junctional nevocytes (P Ͻ .001) and more intense HMB-45 cytoplasmic staining than junctional zone nevocytes.Conclusions: S-100 and MART-1 were not useful in separating benign from malignant lesions. Results for nevus cells beneath the junctional zone were overwhelmingly negative for HMB-45 and Ki-67. Two nevi and all melanomatous nodules were positive for HMB-45 (PϽ.001). A higher Ki-67 proliferation index convincingly separated melanomas from nevi (P Ͻ .001). Immunostaining for HMB-45 and Ki-67 are valuable adjuncts to careful histopathologic evaluation in assessing benign and malignant conjunctival melanocytic tumors.

Usefulness of a Red Chromagen in the Diagnosis of Melanocytic Lesions of the Conjunctiva

“…In a subsequent study, Keijser et al 24 concluded that Melan-A was a poor marker for conjunctival melanocytes, with 44% of conjunctival melanoma and 30% of PAM specimens showing negative antigenicity. Conversely, other studies 18,23,30 involving similar sample sizes concurred with our findings showing that both the intensity and the pervasiveness of Melan-A staining are stronger in conjunctival melanoma, PAM, and nevi than is S100 immunoreactivity.…”

“…Chowers et al 22 initially evaluated Ki67 in PAM and found an approximately 3-fold increase in Ki67 reactivity with increasing atypia consistent with the outcomes of the present study. Jakobiec et al 18 similarly found increased Ki67 reactivity in conjunctival melanoma rather than in the overlying PAM within the same specimens. However, the usefulness …”

“…Ideally, one would prefer to use 2 single antibodies that display high sensitivity and specificity for staining either all or only atypical, potentially malignant melanocytic lesions. Several markers have been shown 17,18 to label melanomas, but the relative performance of each marker in the conjunctiva remains unclear. In particular, these markers have yet to be evaluated in terms of their usefulness for distinguishing between degrees of atypia in PAM.…”

“…To identify immunohistochemical markers for the characterization of these conjunctival melanocytic lesions, we examined a candidate marker list including melanoma cocktail (anti-Melan-A and HMB45), panmelanoma cocktail (anti-Melan-A, HMB45, and antityrosinase), dPANMEL cock- study, we found dPANMEL, S100, Melan-A, HMB45, and Ki67 to be especially informative, thus making these markers the focus of this study. Several studies 18,[21][22][23][24] have been conducted to assess melanocytic markers in conjunctival tissue. However, many of these did not make direct contrast comparisons or they made nonstatistically powered comparisons between PAM with or without atypia and conjunctival melanoma.…”

“…18 In cutaneous melanomas, S100 has been claimed by some 28 to be more sensitive than Melan-A for the detection of melanocytic cells. In ocular tissues, the usefulness of Melan-A is controversial.…”