Expression of CMV protein pp65 in cutaneous malignant melanoma

Abstract

Human cytomegalovirus (CVM) has been detected by immunohistochemistry (IHC) in brain tumours; however, whether CMV antigen is seen in melanomas has not yet been elucidated. Applying IHC, melanoma tissue was assessed for the expression of pp65, a tegument protein of CMV. Two cohorts were available, cohort-I and II, the latter included also related metastasis. In addition to IHC, in situ hybridisation (ISH) was carried out to assess whether CMV related genetic sequences were detectable in a subset of cases. Seventy per cent of the 142 cases in cohort-I and 50% of the 37 cases in cohort-II displayed immunoreactivity (IR). In both cohorts, the IHC outcome correlated with T-stage (Cohort I: Spearman 0.22, p = 0.01, Cohort II: Fisher exact text 0.04). In 30 of cohort-II cases, when IHC staining was carried out on both the primary tumour and the corresponding metastasis, no change in IR was noted in 53%; in 20%, the IR was lower and in 27% higher in the metastasis when compared with the primary tumour. These results were significant (Fisher exact test 0.03). Applying ISH technique on four tumour cases with detectable pp65 protein, CMV related genetic sequence was not detected. Here, we demonstrate, congruent with observations published for brain tumours, that the protein pp65 is indeed observed in substantial number of melanoma cases with IHC; however, no signal was detected with ISH technique. These findings are in line with previously reported studies, demonstrating that the role of CMV in tumours is still debatable.

Current status of skin cancers with a focus on immunology and immunotherapy

“…Although regional lymph node involvement (stage III) is a part of the metastasis process, only stage IV, in which tumor cells metastasize to distant organs, is considered metastatic melanoma according to the staging, the lymphatic system is the main pathway by which melanoma cells move, despite the hematogenous system occasionally being implicated [ 110 ]. CMV antigen has been detected in several malignancies including gliomas and melanoma, which has prompted researchers to target these antigens as a therapeutic approach [ 111 , 112 ]. In this way recent studies have discovered an effective approach MCMV-derived CD8 + T-cell peptide epitopes as cytotoxic and immunomodulatory agents to promote immediate tumor control and long-term anti-tumor immunity conducive to melanoma cancer [ 112 ].…”

“…CMV antigen has been detected in several malignancies including gliomas and melanoma, which has prompted researchers to target these antigens as a therapeutic approach [ 111 , 112 ]. In this way recent studies have discovered an effective approach MCMV-derived CD8 + T-cell peptide epitopes as cytotoxic and immunomodulatory agents to promote immediate tumor control and long-term anti-tumor immunity conducive to melanoma cancer [ 112 ].…”