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Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
Expression of CMV protein pp65 in cutaneous malignant melanoma
Margrét Agnarsdóttir1,2, Svetlana Popova1,2, Irina Alafuzoff1,2
1Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
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.
Insights
Human cytomegalovirus (CMV) protein pp65 was detected in a significant percentage of melanoma tissues using immunohistochemistry (IHC). However, CMV genetic sequences were not found, suggesting its role in melanoma remains uncertain.
Area of Science:
- Oncology
- Virology
- Immunohistochemistry
Background:
- Human cytomegalovirus (CMV) presence is known in brain tumors.
- The detection of CMV antigens in melanoma has not been previously investigated.
Purpose of the Study:
- To investigate the expression of CMV pp65 protein in melanoma tissues using immunohistochemistry (IHC).
- To determine the presence of CMV genetic sequences in melanoma using in situ hybridization (ISH).
Main Methods:
- Immunohistochemistry (IHC) was applied to assess pp65 protein expression in 142 (cohort I) and 37 (cohort II) melanoma cases, including metastases.
- In situ hybridization (ISH) was performed on a subset of cases to detect CMV genetic material.
- Correlation analysis was conducted between IHC results and T-stage, as well as between primary tumors and metastases.
Main Results:
- Seventy percent of cohort I and 50% of cohort II cases showed pp65 immunoreactivity (IR).
- IHC results correlated with T-stage in both cohorts.
- In cohort II, pp65 IR levels varied between primary melanomas and their corresponding metastases (53% no change, 20% lower, 27% higher).
- ISH did not detect CMV genetic sequences in four tested tumor samples with detectable pp65 protein.
Conclusions:
- CMV pp65 protein is present in a substantial proportion of melanoma cases, similar to brain tumors.
- The absence of detectable CMV genetic sequences via ISH indicates that the presence of pp65 protein may not signify active CMV infection.
- The findings suggest that the role of CMV in melanoma pathogenesis requires further investigation and remains debatable.
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