Virology Journal | |
Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients | |
Masanori Daibata2  Takao Fukaya3  Mutsuo Furihata1  Nagamasa Maeda3  Hiroyoshi Oguri3  Yuiko Nemoto2  Yumiko Hashida2  Masayuki Imajoh2  | |
[1] Department of Pathology, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan;Department of Microbiology and Infection, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan;Department of Obstetrics and Gynecology, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan | |
关键词: HPV typing; Cervical adenocarcinoma; Cervical squamous cell carcinoma; Merkel cell polyomavirus; | |
Others : 1154209 DOI : 10.1186/1743-422X-9-154 |
|
received in 2011-11-30, accepted in 2012-07-27, 发布年份 2012 | |
【 摘 要 】
Background
Merkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV). In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs) were also studied.
Results
Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR) and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16 cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs.
Conclusions
This study provides the first observation that MCPyV coexists in a subset of HPV-associated cervical cancers from Japanese patients. The prevalence of MCPyV in these lesions was close to that observed in the cutaneous SCCs. Further worldwide epidemiological surveys are warranted to determine the possible association of MCPyV with pathogenesis of cervical cancers.
【 授权许可】
2012 Imajoh et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150407103026750.pdf | 1945KB | download | |
Figure 3. | 151KB | Image | download |
Figure 2. | 77KB | Image | download |
Figure 1. | 76KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008, 319:1096-1100.
- [2]Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Peñas PF, Nghiem P: Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol 2008, 58:375-381.
- [3]Becker JC, Houben R, Ugurel S, Trefzer U, Pföhler C, Schrama D: MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol 2009, 129:248-250.
- [4]Busam KJ, Jungbluth AA, Rekthman N, Coit D, Pulitzer M, Bini J, Arora R, Hanson NC, Tassello JA, Frosina D, Moore P, Chang Y: Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas. Am J Surg Pathol 2009, 33:1378-1385.
- [5]Carter JJ, Paulson KG, Wipf GC, Miranda D, Madeleine MM, Johnson LG, Lemos BD, Lee S, Warcola AH, Iyer JG, Nghiem P, Galloway DA: Association of Merkel cell polyomavirus-specific antibodies with Merkel cell carcinoma. J Natl Cancer Inst 2009, 101:1510-1522.
- [6]Duncavage EJ, Zehnbauer BA, Pfeifer JD: Prevalence of Merkel cell polyomavirus in Merkel cell carcinoma. Mod Pathol 2009, 22:516-521.
- [7]Garneski KM, Warcola AH, Feng Q, Kiviat NB, Leonard JH, Nghiem P: Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol 2009, 129:246-248.
- [8]Helmbold P, Lahtz C, Enk A, Herrmann-Trost P, Marsch WC, Kutzner H, Dammann RH: Frequent occurrence of RASSF1A promoter hypermethylation and Merkel cell polyomavirus in Merkel cell carcinoma. Mol Carcinog 2009, 48:903-909.
- [9]Kassem A, Schöpflin A, Diaz C, Weyers W, Stickeler E, Werner M, Zur Hausen A: Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res 2008, 68:5009-5013.
- [10]Mangana J, Dziunycz P, Kerl K, Dummer R, Cozzio A: Prevalence of Merkel cell polyomavirus among Swiss Merkel cell carcinoma patients. Delmatology 2010, 221:184-188.
- [11]Paolini F, Donati P, Amantea A, Bucher S, Migliano E, Venuti A: Merkel cell polyomavirus in Merkel cell carcinoma of Italian patients. Virol J 2011, 8:103. BioMed Central Full Text
- [12]Paulson KG, Lemos BD, Feng B, Jaimes N, Peñas PF, Bi X, Maher E, Cohen L, Leonard JH, Granter SR, Chin L, Nghiem P: Array-CGH reveals recurrent genomic changes in Merkel cell carcinoma including amplification of L-Myc. J Invest Dermatol 2009, 129:1547-1555.
- [13]Sihto H, Kukko H, Koljonen V, Sankila R, Böhling T, Joensuu H: Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma. J Natl Cancer Inst 2009, 101:938-945.
- [14]Touzé A, Gaitan J, Maruani A, Le Bidre E, Doussinaud A, Clavel C, Durlach A, Aubin F, Guyétant S, Lorette G, Coursaget P: Merkel cell polyomavirus strains in patients with merkel cell carcinoma. Emerg Infect Dis 2009, 15:960-962.
- [15]Varga E, Kiss M, Szabó K, Kemény L: Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas. Br J Dermatol 2009, 161:930-932.
- [16]Katano H, Ito H, Suzuki Y, Nakamura T, Sato Y, Tsuji T, Matsuo K, Nakagawa H, Sata T: Detection of Merkel cell polyomavirus in Merkel cell carcinoma and Kaposi’s sarcoma. J Med Virol 2009, 81:1951-1958.
- [17]Kuwamoto S, Higaki H, Kanai K, Iwasaki T, Sano H, Nagata K, Kato K, Kato M, Murakami I, Horie Y, Yamamoto O, Hayashi K: Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma. Hum Pathol 2011, 42:632-640.
- [18]Nakajima H, Takaishi M, Yamamoto M, Kamijima R, Kodama H, Tarutani M, Sano S: Screening of the specific polyoma virus as diagnostic and prognostic tools for Merkel cell carcinoma. J Dermatol Sci 2009, 56:211-213.
- [19]Calder KB, Smoller BR: New insights into merkel cell carcinoma. Adv Anat Pathol 2010, 17:155-161.
- [20]Lucarz A, Brand G: Current considerations about Merkel cells. Eur J Cell Biol 2007, 86:243-251.
- [21]Moll I, Roessler M, Brandner JM, Eispert AC, Houdek P, Moll R: Human Merkel cells–aspects of cell biology, distribution and functions. Eur J Cell Biol 2005, 84:259-271.
- [22]McCluggage WG, Kennedy K, Busam KJ: An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly TTF1 positive and which may express CK20 and P63. Am J Surg Pathol 2010, 34:525-532.
- [23]Shuda M, Arora R, Kwun HJ, Feng H, Sarid R, Fernández-Figueras MT, Tolstov Y, Gjoerup O, Mansukhani MM, Swerdlow SH, Chaudhary PM, Kirkwood JM, Nalesnik MA, Kant JA, Weiss LM, Moore PS, Chang Y: Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int J Cancer 2009, 125:1243-1249.
- [24]Bialasiewicz S, Lambert SB, Whiley DM, Nissen MD, Sloots TP: Merkel cell polyomavirus DNA in respiratory specimens from children and adults. Emerg Infect Dis 2009, 15:492-494.
- [25]Goh S, Lindau C, Tiveljung-Lindell A, Allander T: Merkel cell polyomavirus in respiratory tract secretions. Emerg Infect Dis 2009, 15:489-491.
- [26]Babakir-Mina M, Ciccozzi M, Lo Presti A, Greco F, Perno CF, Ciotti M: Identification of Merkel cell polyomavirus in the lower respiratory tract of Italian patients. J Med Virol 2010, 82:505-509.
- [27]Abedi Kiasari B, Vallely PJ, Klapper PE: Merkel cell polyomavirus DNA in immunocompetent and immunocompromised patients with respiratory disease. J Med Virol 2011, 83:2220-2224.
- [28]Wieland U, Mauch C, Kreuter A, Krieg T, Pfister H: Merkel cell polyomavirus DNA in persons without Merkel cell carcinoma. Emerg Infect Dis 2009, 15:489-491.
- [29]Wieland U, Kreuter A: Merkel cell polyomavirus infection and Merkel cell carcinoma in HIV-positive individuals. Curr Opin Oncol 2011, 23:488-493.
- [30]Boukamp P: UV-induced skin cancer: similarities–variations. J Dtsch Dermatol Ges 2005, 3:493-503.
- [31]Al-Ahmadie HA, Mutasim DF, Mutema GK: A case of intraepidermal Merkel cell carcinoma within squamous cell carcinoma in-situ: Merkel cell carcinoma in-situ? Am J Dermatopathol 2004, 26:230-233.
- [32]Noreen MG, Walsh NM: Primary neuroendocrine (Merkel cell) carcinoma of the skin: morphologic diversity and implications thereof. Hum Pathol 2001, 32:680-689.
- [33]Sirikanjanapong S, Melamed J, Patel RR: Intraepidermal and dermal Merkel cell carcinoma with squamous cell carcinoma in situ: a case report with review of literature. J Cutan Pathol 2010, 37:881-885.
- [34]Dworkin AM, Tseng SY, Allain DC, Iwenofu OH, Peters SB, Toland AE: Merkel cell polyomavirus in cutaneous squamous cell carcinoma of immunocompetent individuals. J Invest Dermatol 2009, 129:2868-2874.
- [35]Kassem A, Technau K, Kurz AK, Pantulu D, Löning M, Kayser G, Stickeler E, Weyers W, Diaz C, Werner M, Nashan D, Zur Hausen A: Merkel cell polyomavirus sequences are frequently detected in nonmelanoma skin cancer of immunosuppressed patients. Int J Cancer 2009, 125:356-361.
- [36]Reisinger DM, Shiffer JD, Cognetta AB Jr, Chang Y, Moore PS: Lack of evidence for basal or squamous cell carcinoma infection with Merkel cell polyomavirus in immunocompetent patients with Merkel cell carcinoma. J Am Acad Dermatol 2010, 63:400-403.
- [37]Ridd K, Yu S, Bastian BC: The presence of polyomavirus in non-melanoma skin cancer in organ transplant recipients is rare. J Invest Dermatol 2009, 129:250-252.
- [38]Murakami M, Imajoh M, Ikawa T, Nakajima H, Kamioka M, Nemoto Y, Ujihara T, Uchiyama J, Matsuzaki S, Sano S, Daibata M: Presence of Merkel cell polyomavirus in Japanese cutaneous squamous cell carcinoma. J Clin Virol 2011, 50:37-41.
- [39]Nakamura T, Sato Y, Watanabe D, Ito H, Shimonohara N, Tsuji T, Nakajima N, Suzuki Y, Matsuo K, Nakagawa H, Sata T, Katano H: Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma. Virology 2010, 398:273-279.
- [40]Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, Chang Y: T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci USA 2008, 105:16272-16277.
- [41]Sihto H, Kukko HM, Koljonen VS, Sankila R, Bohling T, Joensuu HT: Merkel cell polyomavirus infection, large T antigen, retinoblastoma protein and outcome in merkel cell carcinoma. Clin Cancer Res 2011, 17:4806-4813.
- [42]Houben R, Adam C, Baeurle A, Hesbacher S, Grimm J, Angermeyer S, Henzel K, Hauser S, Elling R, Bröcker EB, Gaubatz S, Becker JC: An intact retinoblastoma protein-binding site in Merkel cell polyomavirus large T antigen is required for promoting growth of Merkel cell carcinoma cells. Int J Cancer 2012, 130:847-856.
- [43]Houben R, Shuda M, Weinkam R, Schrama D, Feng H, Chang Y, Moore PS, Becker JC: Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens. J Virol 2010, 84:7064-7072.
- [44]Legrand B, Mazancourt P, Durigon M, Khalifat V, Crainic K: DNA genotyping of unbuffered formalin fixed paraffin embedded tissues. Forensic Sci Int 2002, 125:205-211.
- [45]Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, Snijders PJ, Meijer CJ: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003, 348:518-527.
- [46]Miura S, Matsumoto K, Oki A, Satoh T, Tsunoda H, Yasugi T, Taketani Y, Yoshikawa H: Do we need a different strategy for HPV screening and vaccination in East Asia? Int J Cancer 2006, 119:2713-2715.
- [47]Houben R, Grimm J, Willmes C, Weinkam R, Becker JC, Schrama D: Merkel cell carcinoma and Merkel cell polyomavirus: evidence for hit-and-run oncogenesis. J Invest Dermatol 2012, 132:254-256.
- [48]de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ, Snijders PJ: The use of general primers GP5 and GP6 elongated at their 3’ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 1995, 76:1057-1062.
- [49]Bhatia K, Goedert JJ, Modali R, Preiss L, Ayers LW: Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression. Int J Cancer 2010, 126:2240-2246.