Merkel Cell Polyomavirus

Abstract

The recently described Merkel cell polyomavirus (MCPyV) is reportedly present in 50% to 80% of Merkel cell carcinomas (MCC). Although the virus has been shown to be absent from other cutaneous neoplasms, its association with malignancies that are histologically similar to MCC, specifically small cell carcinoma of the lung and other high-grade neuroendocrine tumors, has yet to be thoroughly investigated. To address this issue, we identified a set of 74 cases of visceral high-grade neuroendocrine tumors from a variety of anatomic sites, including 32 cases from the lung, 16 cases from the gastrointestinal tract, 20 cases from the female reproductive system, 3 cases from soft tissue, 2 cases from the head and neck region, and 1 case from the bladder. Using a set of primers optimized to detect MCPyV in formalin-fixed tissue, polymerase chain reaction (PCR)-based testing showed evidence of MCPyV DNA in only 1 of the 74 tumors; however, clinicopathologic review of the positive case (a neuroendocrine tumor of the small intestine) disclosed that the patient had a history of primary MCC of the buttock. PCR-based testing also showed no evidence of the related WU and KI polyomaviruses in the set of 74 cases. We conclude that, when evaluated by PCR-based testing, MCPyV is a specific marker for MCC that can be helpful in distinguishing cases of metastatic MCC from other high-grade neuroendocrine tumors. Our results also suggest that MCPyV does not have a role in the oncogenesis of visceral high-grade neuroendocrine tumors.

Distinct Merkel Cell Polyomavirus Molecular Features in Tumour and Non Tumour Specimens from Patients with Merkel Cell Carcinoma

“…The close association between MCPyV and MCC has been confirmed in several case series worldwide [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. However, MCPyV has been detected in normal skin [23], benign skin lesions [24] and non MCC skin cancer [25], and also found in various tissues such as the oral cavity [26], gastrointestinal and urogenital tracts [23], tonsils [27], respiratory tract [28], blood [9], and rarely in non skin cancers [19], [25], [29], [30].…”

No Evidence of Human Polyomavirus 9, WU and KI DNA in Kidney and Urinary Bladder Tumour Tissue Samples

“…In total, 37 and 38 formalin-fixed paraffin-embedded, mucosal melanoma samples [45,55], 25 fresh-frozen, central nervous system tumours, 31 fresh-frozen, neuroblastoma samples [46], 50 neonatal, dried blood spots from children who developed later acute lymphoblastic leukaemia [50], 43 formalin-fixed paraffin-embedded neuroendocrine tumour samples [48], 30 fresh lung adenocarcinomas [49] and 32 neuroendocrine lung tumours [47] were found to be negative for KIPyV and WUPyV DNA by standard [45,46,47], nested [50], real-time PCR [49] and polyomavirus genotyping assay [48]. Babakir-Mina et al [63] detected the VP1 region of KIPyV in 9 out of 40 fresh lung cancer tissue samples, although only 2 malignant tissue samples were positive for the early region of KI virus.…”

“…Some publications about the prevalence of KIPyV, WUPyV and HPyV9 in different tumours are available, but these viruses have not been hitherto examined in bladder and renal cancers [45,46,47,48,49,50,51,52,53,54,55,56,57]. In the present study the prevalence of KIPyV, WUPyV, HPyV9 and BKPyV were examined by PCR in tissue samples from the urinary tract.…”

Merkel Cell Carcinoma: A Virus-Induced Human Cancer

“…MCV-related and MCV-unrelated MCC tumors may have different pathoetiologies and prognoses (49). Viral antigens are readily detected in most MCC tumors with high copy number integrants (20, 50, 51) and are useful for distinguishing MCV-positive MCCs from other tumors (52, 53).…”