Association of Merkel Cell Polyomavirus-Specific Antibodies With Merkel Cell Carcinoma

Association of Merkel Cell Polyomavirus-Specific

Antibodies With Merkel Cell Carcinoma

J Natl Cancer Inst. 2009 Sep 23

Carter JJ, Paulson KG, Wipf GC, Miranda D, Madeleine MM, Johnson LG, Lemos BD, Lee S,Warcola AH, Iyer JG, Nghiem P, Galloway DA.

Affiliations of authors: Program in Cancer Biology (JJC, GCW, DM, DAG), Division of Human Biology (JJC, MMM, LGJ, DAG), Division of Public Health Sciences (JJC, MMM, LGJ, DAG), and Division of Clinical Research (PN), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Microbiology (DAG), Department of Pathology (KGP, SL, PN), Department of Epidemiology (MMM), Department of Dermatology/Medicine (KGP, BDL, SL, AHW, JGI, PN), University of Washington, Seattle, WA.

Correspondence to: Denise A. Galloway, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M.S. C1-105, Seattle, WA 98109-1024 (e-mail: dgallowa@fhcrc.org).

Background Merkel cell polyomavirus (MCPyV) has been detected in approximately 75% of patients with the rare skin cancer Merkel cell carcinoma. We investigated the prevalence of antibodies against MCPyV in the general population and the association between these antibodies and Merkel cell carcinoma. Methods Multiplex antibody-binding assays were used to assess levels of antibodies against polyomaviruses in plasma. MCPyV VP1 antibody levels were determined in plasma from 41 patients with Merkel cell carcinoma and 76 matched control subjects. MCPyV DNA was detected in tumor tissue specimens by quantitative polymerase chain reaction. Seroprevalence of polyomavirus-specific antibodies was determined in 451 control subjects. MCPyV strain-specific antibody recognition was investigated by replacing coding sequences from MCPyV strain 350 with those from MCPyV strain w162. Results We found that 36 (88%) of 41 patients with Merkel cell carcinoma carried antibodies against VP1 from MCPyV w162 compared with 40 (53%) of the 76 control subjects (odds ratio adjusted for age and sex = 6.6, 95% confidence interval [CI] = 2.3 to 18.8). MCPyV DNA was detectable in 24 (77%) of the 31 Merkel cell carcinoma tumors available, with 22 (92%) of these 24 patients also carrying antibodies against MCPyV. Among 451 control subjects from the general population, prevalence of antibodies against human polyomaviruses was 92% (95% CI = 89% to 94%) for BK virus, 45% (95% CI = 40% to 50%) for JC virus, 98% (95% CI = 96% to 99%) for WU polyomavirus, 90% (95% CI = 87% to 93%) for KI polyomavirus, and 59% (95% CI = 55% to 64%) for MCPyV. Few case patients had reactivity against MCPyV strain 350; however, indistinguishable reactivities were found with VP1 from strain 350 carrying a double mutation (residues 288 and 316) and VP1 from strain w162. Conclusion Infection with MCPyV is common in the general population. MCPyV, but not other human polyomaviruses, appears to be associated with Merkel cell carcinoma.

Journal National Cancer institute

Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study.

Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study.
J Cutan Pathol. 2009 Jul 21

Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE.
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City.

Correspondence to Jorge Albores-Saavedra, MD, Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion, Vasco de Quiroga 15, Col. Seccion XVI, Salvador Zubiran, Mexico City Tlalpan, CP 14000, MexicoTel: + 52 55 548 70900Fax: + 52 55 548 53489e-mail:alboresjorge@yahoo.com

Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor arising predominantly on sun-exposed skin of older and usually immunosuppressed individuals.

Methods: Using data from NCI's SEER (Surveillance, Epidemiology, and End Results) Program from 1973 to 2006, we analyzed the demographics and survival of MCC.

Results: SEER had recorded 3870 cases of MCC. The incidence was higher in men (2380 cases, 61.5%) than in women (1490 cases, 38.5%). Most patients were White (94.9%) between 60 and 85 years of age. MCC was rare in Blacks. The most common location was the head and neck. The salivary glands, nasal cavity, lip, lymph nodes, vulva, vagina and esophagus were the most common extracutaneous sites. The 10-year relative survival rate was higher in women than men (64.8% vs. 50.5%, p <>

Conclusions: MCC arises predominantly in the skin of head and neck in White men above 70 years of age. Cases also occurred in extracutaneous sites. Age did not predict survival, yet gender, site and tumor size revealed clear differences. The most significant predictor of survival was tumor stage.

Wiley InterScience

Quantitation of human seroresponsiveness to Merkel cell polyomavirus.

Quantitation of human seroresponsiveness to Merkel cell polyomavirus.
PLoS Pathog. 2009 Sep

Pastrana DV, Tolstov YL, Becker JC, Moore PS, Chang Y, Buck CB.
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, USA.

Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further investigate the role of MCV infection in the development of MCC, we developed a reporter vector-based neutralization assay to quantitate MCV-specific serum antibody responses in human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48) of adult subjects without MCC were MCV seropositive, the geometric mean titer of the control group was 59-fold lower than the MCC patient group (p less then 0.0001). protein, Only 4% (2/48) of control subjects displayed neutralizing titers greater than the mean titer of the MCV-positive MCC patient population. MCC tumors were found not to express detectable amounts of MCV VP1 capsid protein, suggesting that the strong humoral responses observed in MCC patients were primed by an unusually immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor itself. The occurrence of highly immunogenic MCV infection in MCC patients is unlikely to reflect a failure to control polyomavirus infections in general, as seroreactivity to BK polyomavirus was similar among MCC patients and control subjects. The results support the concept that MCV infection is a causative factor in the development of most cases of MCC. Although MCC tumorigenesis can evidently proceed in the face of effective MCV-specific antibody responses, a small pilot animal immunization study revealed that a candidate vaccine based on MCV virus-like particles (VLPs) elicits antibody responses that robustly neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine could be effective for preventing the initial establishment of MCV infection.

PubMed

The Interdisciplinary Treatment of Merkel Cell Carcinoma: A Retrospective Case Analysis and Review of the Current Literature.

The Interdisciplinary Treatment of Merkel Cell Carcinoma: A Retrospective Case Analysis and Review of the Current Literature.
Zentralbl Chir. 2009 Sept

Strub B, Weindel S, Witt P, Grünert J.
Klinik für Hand-, Plastische und Wiederherstellungschirurgie Kantonsspital St. Gallen, Schweiz.

BACKGROUND: Merkel cell carcinoma is a rare, -aggressive, neuroendocrine malignancy of the skin. Over the period from June 2005 to January 2007 (18 months) 7 Merkel cell carcinomas in different tumour stages and localisations were -treated in our department for hand, plastic and reconstructive surgery. Given an incidence rate of approximately 0.1-0.4 per 100 000 habitants, this accumulation of cases is considerably higher than would be statistically expected. This led us to analyse our cases retrospectively and provided the opportunity to discuss the treatment modalities on the basis of the current literature.

PATIENTS AND METHODS: All patients were referred to our clinic after incomplete tumour excision and histopathological diagnosis elsewhere, for fur-ther surgical treatment. Two female and 5 male patients, aged 63 to 83 years, were treated. The patients' data were collected and analysed retrospectively.

RESULTS: In all cases an R0 resection could be achieved, with safety resection margins between 1.5 cm and 4.5 cm. The reconstruction of the resulting defects was achieved by skin transplants in six cases and a primary suture in one case. All patients received adjuvant radiotherapy. Furthermore, three patients received adjuvant chemotherapy due to metastases of the progressed Merkel cell carcinoma. Three patients remained free of recurrence and in two patients a progression of the tumour disease could be impeded, whilst two patients succumbed to their disease.

CONCLUSIONS: In the case of an early diagnosis, an R0 resection can usually be achieved. A safety -resection margin of a minimum of 1.5 cm in the face and 3 cm for localisation on the extremities should be obtained. To reduce the local recurrence rate, adjuvant radiotherapy should be conducted. The benefit from chemotherapy still -remains unclear. © Georg Thieme Verlag Stuttgart ˙ New York.

PubMed