Detection and quantification of Merkel cell polyomavirus. Analysis of Merkel cell carcinoma cases from 1977 to 2015

Abstract

This study investigates the presence of Merkel cell polyomavirus (MCPyV) in skin lesions of patients with Merkel cell carcinoma (MCC). MCPyV was quantified using quantitative Real-Time-PCR (qRT-PCR) in 34 paraffinized MCC samples (resected/biopsied) originally taken between 1977 and 2015, and six non-MCC samples. In 31 (91.2%) MCC-individuals, MCPyV was detected. No virus was observed in any non-MCC tumor. Average age at diagnosis was 78.2 ± 9.35 (55-97) years for women (n = 19) and 69.5 ± 14.7 (45-91) for men (n = 15) (P = 0.04). MCC tumor location, known in 25 cases, was: 11 (44%) in the head region, 6 (24%) in upper limbs, 4 (16%) in lower limbs, and 4 (16%) in the trunk. All but one patient had received some sort of treatment: 15 (45.45%) underwent both radio and chemotherapy, 13 (39.39%) only surgery, 2 (6.06%) surgery, plus radio and chemotherapy, 2 (6.06%) surgery and chemotherapy, and 1 (3.03%) only radiotherapy. Follow up data were available for 21/34 patients: recurrence was recorded for 4 (19.04%), and metastasis for 13 (61.9%). Recorded data showed that 10 men and 5 women (total 44.1%) died during follow up, 7 (46.7%) of them within 2 years of diagnosis. Viral load was 5.8 ± 1.4 log copies/10 cells (3.1-8.6), independent of any variable. MCPyV was very frequent in MCC. It was principally associated with head and limb tumors, it more commonly affected men, who in this study were, on average, younger than women, and had high rates of recurrence and mortality. The amplification techniques described here are easily applied and suitable for detecting the presence of MCPyV virus in MCC.

Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma

“…A putative reason, however, may be the observation that tumors in females were diagnosed more frequently in older patients (median age females 77.0 years vs. median age males 70.5). In line with that, Álvarez-Argüelles et al recently speculated that there may an immunosuppressive component due to age contributing to the sex effect in MCPyV detection demonstrated in their analyses and in our study (44). Unfortunately we could not prove an association of age and viral load in our data.…”

Expression of 3q oncogene SEC62 in atypical fibroxanthoma‑immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features

“…There is growing evidence that viruses play an important role in tumorigenesis, mainly in immunosuppressed patients and an estimated 20% of global cancer burden is related to viral infections (44). Merkel Cell Polyomavirus (MCPyV) was recently detected in Merkel cell carcinoma (MCC) and approximately 91.2% of MCC are MCPyV-positive (41,45). Intriguingly, 85% of all healthy adults and 58% of children younger than 10 years are MCPyV-positive displaying a high seroprevalence of MCPyV (46).…”

Viral Oncology: Molecular Biology and Pathogenesis

“…Simian virus 40 (SV40) and the human polyomaviruses JC and BK belong to the same family [ 127 ]. MCPyV is the only polyomavirus that is known to be oncogenic [ 128 , 129 , 130 , 131 , 132 , 133 ] and is found in 80–97% of Merkel cell carcinoma (MCC) [ 127 , 134 , 135 ]. MCC is an extremely rare and aggressive cutaneous cancer with an incidence and mortality rates of 0.79 and 0.43 per 100,000, respectively [ 136 ].…”

“…In addition to the mutation causing clonal integration, a second mutation is necessary for MCC development. Perhaps the requirement of these two mutations is why MCC is exceedingly rare, despite cutaneous MCPyV infection being common [ 134 ]. The second mutation may arise from UV radiation [ 175 ] and results in the truncated form of the LT antigen [ 129 ] ( Figure 4 ).…”