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7. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

Author

Mantovani, Giovanna, Bastepe, Murat, Monk, David, de Sanctis, Luisa, Thiele, Susanne, Usardi, Alessia, Ahmed, S. Faisal, Bufo, Roberto, Choplin, Timothée, De Filippo, Gianpaolo, Devernois, Guillemette, Eggermann, Thomas, Elli, Francesca M., Freson, Kathleen, García Ramirez, Aurora, Germain-Lee, Emily L., Groussin, Lionel, Hamdy, Neveen, Hanna, Patrick, Hiort, Olaf, Jüppner, Harald, Kamenický, Peter, Knight, Nina, Kottler, Marie-Laure, Le Norcy, Elvire, Lecumberri, Beatriz, Levine, Michael A., Mäkitie, Outi, Martin, Regina, Martos-Moreno, Gabriel Ángel, Minagawa, Masanori, Murray, Philip, Pereda, Arrate, Pignolo, Robert, Rejnmark, Lars, Rodado, Rebecca, Rothenbuhler, Anya, Saraff, Vrinda, Shoemaker, Ashley H., Shore, Eileen M., Silve, Caroline, Turan, Serap, Woods, Philip, Zillikens, M. Carola, Perez de Nanclares, Guiomar, and Linglart, Agnès

Published
2018
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9. Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial

Author

Normanno, N., Rachiglio, A.M., Lambiase, M., Martinelli, E., Fenizia, F., Esposito, C., Roma, C., Troiani, T., Rizzi, D., Tatangelo, F., Botti, G., Maiello, E., Colucci, G., Ciardiello, F., Giuliani, F., Simone, G., Febbraro, A., Tommaselli, E., Cinieri, S., Criscuolo, M., Perrino, A., Rinaldi, A., Bordonaro, R., Manusia, M., Romito, S., Bufo, P., Cartenì, G., Biglietto, M., Nappi, O., Cardarelli, A., Montesarchio, E., Micheli, P., Nasti, G., Chicchinelli, N., Iannaccone, A., Russo, A., Cabibi, D., Giaccone, P., Barone, C., Rindi, G., Tonini, G., Onetti Muda, A., Perrone, G., Latiano, T., Graziano, P., Pisconti, S., and Sebastio, A.

Published
2015
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22. 93rd annual convention podium and poster abstracts

Author

Davis, C. M., Strong, S. A., Hellinger, M. D., Williamson, P. R., Larach, S. W., Ferrara, A., Blake, T. B., Medich, D. S., Ziv, Y., Oakley, J. R., Reissman, P., Piccirillo, M., Ulrich, A., Nogueras, J. J., Wexner, S. D., Rubin, M. S., Bodenstein, L. E., Kent, K. C., Williamson, M. E. R., Lewis, W. G., Sagar, P. M., Holdsworth, P. J., Johnston, D., Fazio, V. W., Goldblum, J. R., Sirimarco, M. T., Lavery, I. C., Petras, R. E., Treem, W. R., Cohen, J., Davis, P. M., Hyams, J. S., Eu, K. W., Bartolo, D. C. C., Green, J. D., Riether, R. D., Rosen, L., Stasik, J. J., Sheets, J. A., Reed, J., Khubchandani, I. T., Armitage, N. C., Chapman, M., Hardcastle, J. D., Viamonte, M., Plasencia, G., Wiltz, O., Jacobs, M., Finan, P. J., Passaro, M., Church, J. M., McGannon, E., Wilson, M., Hull-Boiner, S., Kollmorgen, C. F., Meagher, A. P., Wolff, B. G., Pemberton, J. H., Martenson, J. A., Ilstrup, D. M., Moran, M. R., Ramos, A., Rothenberger, D. A., Goldberg, S. M., Johnson, D., Madoff, R. D., Wong, W. D., Finne, III, C. O., Konishi, F., Furuta, K., Kanazawa, K., Lockhart, D., Schmitt, S., Caushaj, P. P., Garcia-Aguilar, J., Belmonte, C., Schiesel, E. C., Mazier, W. P., Senagore, A. J., Piccirillo, M. F., Teoh, T. -A., Yoon, K. -S., Paul, R. A. Patino, Lucas, J., Nelson, R., Norton, N., Cautley, E., Schouten, W. R., Briel, J. W., Auwerda, J. J. A., de Graaf, E. J. R., Lowry, A. C., Sentovich, S. M., Blatchford, G. J., Rivela, L. J., Thorson, A. G., Christensen, M. A., Jorge, J. M. N., Yang, Y. K., Shafik, A., Allendorf, J. D. F., Kayton, M. L., Libutti, S. K., Trokel, M. J., Whelan, R. L., Treat, M. R., Nowygrod, R., Bessler, M., Frank, R. E., Saclarides, T. J., Leurgans, S., Speziale, N. J., Drab, E., Rubin, D., Hull, T. L., Schroeder, T. K., Scholefield, J. H., Ogunbiyi, O. A., Smith, J. H. F., Rogers, K., Sharp, F., Longo, W. E., Vernava, III, A. M., Wade, T. P., Coplin, M. A., Virgo, K. S., Johnson, F. E., Brady, M., Kavolius, J., Quan, S. H. Q., Goldstein, E. T., Feldman, S., Shub, H. A., Bennett, D. R., Kumar, R., McMillen, M. A., Thornton, S., Khoury, D. A., Opelka, F. G., Teoh, T -A., Cohen, S. M., Weiss, E. G., Ortiz, H., De Miguel, M., Armendáriz, P., Rodriguez, J., Chocarro, C., Farouk, R., Dorrance, H. R., Duthie, G. S., Rainey, J. B., Morgado, Jr., P. J., Corman, M. L., Kawamura, Y. J., Sawada, T., Muto, T., Nagai, H., Hill, J., MacLennan, I., Binderow, S. R., Daniel, N., Ehrenpreis, E. D., Jensen, J. E., Bonner, G. F., Ruderman, W. B., Milsom, J. W., Gibbs, D. H., Beck, D. E., Hicks, T. C., Timmcke, A. E., Gathright, Jr, J. B., Cheong, D., Lucas, F. V., McGinity, M., Taylor, B. A., Godwin, P., Holdsworth, P., Lewis, W., Quirke, P., Williamson, M., Kokoszka, J., Pavel, D., Abcarian, H., Stephenson, B. M., Morgan, A. R., Salaman, J. R., Wheeler, M. H., Tran, T. C. K., Willemsen, W., Kuijpers, H. C., Lehman, J. F., Wiseman, J. S., MacFie, J., Sedman, P., May, J., Mancey-Jones, B., Johnstone, D., Nwariaku, F. E., Rochon, R. B., Huber, P. J., Carrico, C. J., Ortega, A., Beart, R., Winchester, D., Steele, G., Green, R., Caushaj, P. F., Devereaux, D., Griffey, S., Reiver, D., Kmiot, W. A., Baker, R., Luchtefeld, M. A., Anthone, G., Schlinkert, R., Roig, J. V., Villoslada, C., Solana, A., Alos, R., Hinojosa, J., Lledo, S., Johnson, D. R. E., Buie, W. D., Jensen, L. L., Heine, J., Hoffmann, B., Timmcke, A., Hicks, T., Opelka, F., Beck, D., Sousa, Jr., A., AraÚjo, S. A., Damico, F. M., Cordeiro, A. C., Pinotti, H. W., Gama, A. H., Fengler, S., Pearl, R., Orsay, C., Seow-Choen, F., Ho, J. M. S., Wiltz, O. H., Torregrosa, M., Brasch, R. C., Bufo, A. J., Krienberg, P., Johnson, G. P., Gowen, G. F., Mullen, P. D., Behrens, D., Hughes, T. G., Wynn, M., Pollack, J. S., Rajagopal, A. S., Huynh, T., Schanbacher, C., Hickson, W. G. E., Yang, Y. -K., Heymen, S., Choi, S. -K., Teoh, T. -A., Wexner, S. D., Vaccaro, C. A., Teoh, T. A., Nogueras, J. J., Choi, S. K., Cheong, D. M. O., Salanga, V. D., MacDonald, A., Baxter, J. N., Finlay, I. G., Mellgren, A., Bremmer, S., Dolk, A., Gillgren, P., Johansson, C., Ahlbäck, S. O., Udén, R., Holmström, B., Ferrara, A., O'Donovan, S., Larach, S. W., Williamson, P. R., Neto, J. A. Reis, Ciquini, S., Quilici, F. A., Reis, Jr., J. A., Torrabadella, L., Salgado, G., Whelan, R. L., Horvath, K. D., Golub, R., Ahsan, H., Cirocco, W., Ziv, Y., Fazio, V. W., Oakley, J. R., Church, J. M., Milsom, J. W., Lavery, L. C., Cohen, S. M., Kmiot, W. A., Reiver, D., Reissman, P., Weiss, E. G., Alós, R., García-Granero, E., Roig, J. V., Uribe, N., Sala, C., Lledo, S., Ozuner, G., Strong, S. A., Bufo, A. J., Daniels, G., Lieberman, R. C., Feldman, S., Lucas, F. V., Longo, W. E., Polites, G., Deshpande, Y., Vernava, A. M., Niehoff, M., Chandel, B., Berglund, D. D., Madoff, R. D., Gemlo, B. T., Spencer, M. P., Goldberg, S. M., Lowry, A. C., Marcello, P. W., Roberts, P. L., Schoetz, D. J., Murray, J. J., Coller, J. A., Veidenheimer, M. C., Koltun, W. A., Bloomer, M. M., Colony, P., Ruggeiro, F., Fleshner, P. R., Michelassi, F., Lewis, W., Williamson, M., Holdsworth, P., Finan, P., Ash, D., Johnston, D., Moran, M. R., Ramos, A., Rothenberger, D. A., Antonenko, D. R., Khanduja, K. S., Fitzgerald, S. D., Meagher, A. P., Moniz-Pereira, P., Wolff, B. G., Outwater, E. K., Marks, G. J., Mohiuddin, M., Sagar, P. M., Hartley, M. N., Mancey-Jones, B., Sedman, P., May, J., MacFie, J., Holbrook, R. F., Rodriguez-Bigas, M. A., Ramakrishnan, K., Palmer, M. L., Petrelli, N. J., Takahashi, T., Nivatvongs, S., Batts, K. P., Lucas, S. W., Klein, S. N., Keidan, R. D., Bannon, J. P., Zhou, J., Armitage, N. C., Hunt, L. M., Robinson, M. H., Hugkulstone, C. E., Clarke, B., Vernon, S. A., Gregson, R. H., Hardcastle, J. D., Ryan, M., Dutta, S., Levine, A., Ortega, A., Anthone, G., Beart, R., Dominguez, J. M., Saclarides, T. J., Bolan, P., Bines, S. D., Adachi, M., Watanabe, T., Sawada, T., Okinaga, K., Muto, T., Hase, K., Shatney, C., Mochizuki, H., Johnson, D., Ure, T., Dehghan, K., Andrus, C. A., Daniel, G. L., D'Emilia, J. C., Rodriguez-Bigas, M., Suh, O. K., Brewer, D. A., Fung, C., Chapuis, P., Bokey, E. L., Garcia, J. C., Banerjee, S., Remzi, F. H., Lavery, I. C., Jorge, J. M. N., Ger, G. C., Gonzalez, L., Gee, A. S., Roe, A. M., Durdey, P., Kaye, M. D., Kyzer, S., Gordon, P. H., Hasegawa, M., Bun, P. Tae, Ikeuchi, D., Onodera, H., Imamura, M., Maetani, S., Blake, T., Hellinger, M., Grewal, H., Klimstra, D. S., Cohen, A. M., Guillem, J. G., Rooney, P. S., Gifford, K. -A., Clarke, P. A., Kuhn, J. A., Bryce, K., Frank, N., Dignan, R. D., Lichliter, W. E., Franko, E., Jacobson, R. M., Preskitt, J. T., Lieberman, Z., Tulanon, P., Steinbach, H., McCarty, T., Simons, T., Plasencia, G., Viamonte, M., Wiltz, O., Jacobs, M., Chen, W. S., Leu, S. Y., Hsu, H., Bessler, M., Halverson, A., Kayton, M. L., Treat, M. R., Nowygrod, R., Congilosi, S., Madoff, R., Wong, W. D., Rothenberger, D., Buie, W. D., Paterson, R., Cartmill, J. A., Trokel, M. J., Gingold, B. S., Cooper, M., Gorfine, S. R., Bauer, J. J., Gelernt, I. M., Kreel, I., Harris, M. T., Vallejo, J. F., Kestenberg, A., Miyajima, N., Kano, N., Ishikawa, Y., Sakai, S., Yamakawa, T., Otchy, D. P., Van Heerden, J. A., Ilstrup, D. M., Weaver, A. L., Winter, L. D., Mav, J., Lee, P. Y., Vetto, J. T., Sullivan, E. S., Rabkin, J., Mayoral, J. L., Matas, A. J., Bove, P., Visser, T., Barkel, D., Villalba, M., Bendick, P., Glover, J., Golub, R. W., Cirocco, W. C., Daniel, N., Altringer, W., Domingues, J. M., Brubaker, L. T., Smith, C. S., Kumar, S., and Gilbert, P.

Published
1994
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33. Podium presentations

Author

Foley, E. F., Marcello, P. W., Roberts, P. L., Murray, J. J., Coller, J. A., Veidenheimer, M. C., Schoetz, D. J., McIntyre, P. B., Pemberton, J. H., Wolff, B. G., Beart, Jr., R. W., Kelly, K. A., Dozois, R. R., Sugita, A., Fukushima, T., Harada, H., Yamamoto, M., Shimada, H., Tjandra, J. J., Fazio, V. W., Milson, J. W., Lavery, I. C., Oakley, J. R., Fabre, J. M., Karch, L. A., Bauer, J. J., Gorfine, S. R., Gelernt, I. M., Metcalf, A. M., Varilek, G., Keck, J. O., Hoffmann, D. C., Sgambati, S. A., Sardella, W. V., Marts, B. C., Longo, W. E., Vernava, III, A. M., Kennedy, D. J., Daniel, G. L., Jones, I., Venkatesh, K. S., Diamond, L. W., Larson, D. M., Ramanujam, P. J., Hicks, J. R., Ellis, C. N., Blakemore, W. S., Nathanson, S. D., Linden, M. D., Tender, P., Zarbo, R. J., Nelson, L., Bannon, J., Marks, G., Zhou, J., Mohiuddin, M., Marks, J., Pollard, C. W., Nivatvongs, S., Rojanasakul, A., Ilstrup, D. M., Speziale, N. J., Saclarides, T. J., Rubin, D. B., Szeluga, D. J., Morgado, P. J., Gomez, L. G., Morgado, Jr., P. J., Neto, J. A. Reis, Quilici, F. A., Cordeiro, F., Reis, Jr., J. A., Nitecki, S., Benn, P., Sarr, M. G., Weiland, L. H., Elhadad, A., Rouffet, F., Baillet, P., Akasu, T., Moriya, Y., Hojo, K., Sugihara, K., Oshima, H., Liu, S. K., Church, J. M., Kirkpatrick, J. R., Danielson, C. L., Dominguez, J. M., Jakate, S. M., Savin, M. H., Altringer, W. J., Lee, C. S., Spencer, M. P., Madoff, R. D., Barrett, R. C., Oster, M. A., Durdey, P., Stein, B. L., Staniunas, R. J., Grewal, H., Guillem, J. G., Quan, S., Enker, W. E., Cohen, A. M., van Tets, W. F., Kuijpers, H. C., Kerner, B. A., Wise, Jr., W. E., Golub, R. W., Arnold, M. W., Aguilar, P. S., Pernikoff, B. J., Eisenstat, T. E., Rubin, R. J., Oliver, G. C., Salvati, E. P., Lunniss, P. J., Sultan, A. H., Barker, P. G., Armstrong, P., Bartram, C. I., Phillips, R. K. S., Schouten, W. R., Briel, J. W., Auwerda, J. J. A., Harnsberger, J. R., Robbins, P. L., Brabbee, G. W., Ryhammer, A. M., Bek, K. M., Hanberg-Sørensen, F., Laurberg, S., Hoff, S. D., Bailey, H. R., Butts, D. R., Max, E., Smith, K. W., Zamora, L. F., Skakun, G. B., Khanduja, K. S., Lee, H., Beart, R. W., Spencer, R., Wiseman, J. S., Senagore, A. J., Bain, I. M., Oliff, J., Min, L., Neoptolomos, J., Keighley, M. R. B., O'Kelly, T. J., Davies, J., Brading, A. F., Mortensen, N. J. McC, Park, J. -G., Han, H. J., Kang, M. S., Nakamura, Y., Goldberg, G. S., Orkin, B. A., Smith, L. E., Fleshner, P. R., Freilich, M. I., Meagher, A. P., Adams, W. J., Lubowski, D. Z., King, D. W., Moran, M., Opelka, F., Timmcke, A., Hicks, T., Gathright, Jr., J. B., Leu, S. Y., Hsu, H., Dean, P. A., Ramsey, P. S., Nelson, H., Philpott, G., Siegel, B., Schwarz, S., Fleshman, J., Welch, M., Connett, J., Buie, W. D., Johnson, D. R., Heine, J. A., Wong, W. D., Rothenberger, D. A., Goldberg, S. M., Shafik, A., MacDonald, A., Craig, J. W., Finlay, I. G., Baxter, J. N., Muir, T. C., Parikh, S., Gold, R. P., Gottesman, L., Annibali, R., Öresland, T., Hallgren, T., Fasth, S., Hultén, L., Farouk, R., Duthie, G. S., MacGregor, A. B., Bartolo, D. C. C., Williamson, M. E. R., Lewis, W. G., Holdsworth, P. J., Hall, N., Finan, P. J., Johnston, D., Seow-Choen, F., Goh, H. S., Motson, R. W., Walsh, C. J., Mooney, E., Yamashita, H. J., Wise, W. E., Hartmann, R. F., Seccia, M., Menconi, C., Ghiselli, G., Cavina, E., Salomon, M. C., Ferrara, A., Larach, S. W., Williamson, P. R., Bass, E. M., Orsay, C. P., Firfer, B., Ramakrishnan, V., Abcarian, H., Bufo, A. J., Feldman, S., Daniels, G. A., Lieberman, R. C., Loder, P. B., Kamm, M. A., Nicholls, R. J., Kum, C. K., Ngoi, S. S., Goh, P. M. Y., Tekant, Y., Isaac, J. R., Gerstle, J. T., Kauffman, G. L., and Koltun, W. A.

Published
1993
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35. The role of the innate immune response in HPV-related oral and oropharyngeal cancer

Author

Pannone, G, Santoro, A, Lo Muzio, L, Leonardi, R, Bufo, P., CAMPISI, Giuseppina, Pannone, G, Santoro, A, Campisi, G, Lo Muzio, L, Leonardi, R, and Bufo, P

Subjects
HPV, oral and oropharyngeal cancer
Abstract

Introduction. During the last 20 years, the incidence of HPV-associated oropharyngeal cancer is increased. Principal actors of the innate immune response against HPV are represented by the TLRs (Toll like receptors). On the other hand different studies have reported that HPV can directly inhibit the functions of the TLRs pathway through interferons (IFNs). There are very few preliminary studies on the role of TLRs mediated HPV clearance in human oncology. Our study aim has been to evaluate whether TLR4 identifies HR-HPV integration state in OSCC. Methods. Protein levels of TLR4 in OSCC were assessed using Immunohistochemistry (IHC). In situ hybridization (ISH) for HPV-DNA detection in morphological context and Pyro-sequencing method have been performed in order to detect viral integration or episomic status. The relationship between TLR expression with or without HPV infection has been elucidated. Results. ISH HPV positive samples have reported lower TLR4 intensity than negative samples and it has confirmed by statistically significant difference (p = .002). There is no statistical correlation between TLR4 intensity and PCR HPV results (p > 0.05). Point-biserial correlation coefficient revealed statistically significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). Conclusions. We retain that TLR4 down-regulation is not associated to the histological tumoral grade but rather to HPV-16 infection and to its integration state into the host DNA.

Published
2014

36. Toll-Like Receptor 4 Expression in the Epithelium of Inflammatory Periapical Lesions

Author

Leonardi, R., Perrotta, R.E., Loreto, C., Musumeci, G., Crimi, S., dos Santos, J.N., Rusu, M.C., Bufo, P., Barbato, E., and Pannone, G.

Subjects
Adult, Inflammation, Male, Radicular Cyst, Cell Survival, Brief Report, Epithelial Cells, Middle Aged, Immunohistochemistry, radicular cysts, Toll-Like Receptor 4, periapical inflammatory granulomas, Gene Expression Regulation, Humans, Female, TLR4
Abstract

Toll-like receptors (TLR) are essential for the innate immune response against invading pathogens and have been described in immunocompetent cells of areas affected by periapical disease. Besides initiating the inflammatory response, they also directly regulate epithelial cell proliferation and survival in a variety of settings. This study evaluates the in situ expression of TLR4 in periapical granulomas (PG) and radicular cysts, focusing on the epithelial compartment. Twenty-one periapical cysts (PC) and 10 PG were analyzed; 7 dentigerous non-inflamed follicular cyst (DC) served as control. TLR4 expression was assessed by immunohistochemistry. TLR4 immunoreaction products were detected in the epithelium of all specimens, with a higher percentage of immunostained cells in PG. Although TLR4 overexpression was detected in both PG and PC, there were differences that seemed to be related to the nature of the lesion, since in PG all epithelial cells of strands, islands and trabeculae were strongly immunoreactive for TLR4, whereas in PC only some areas of the basal and suprabasal epithelial layers were immunostained. This staining pattern is consistent with the action of TLR4: in PG it could promote formation of epithelial cell rests of Malassez and in epithelial strands and islands the enhancement of cell survival, proliferation and migration, whereas in PC TLR4 could protect the lining epithelium from extensive apoptosis. These findings go some way towards answering the intriguing question of why many epithelial strands or islands in PG and the lining epithelium of apical cysts regress after non-surgical endodontic therapy, and suggest that TLR4 plays a key role in the pathobiology of the inflammatory process related to periapical disease.

Published
2015

37. Beta-catenin and surviving expression in keratocystic odontogenic tumor (KCOT). A comparative immunohistochemical study in primary, recurrent and nevoid basal cell carcinoma syndrome (NBCCS)-associated lesions

Author

Leonardi, R., Matthews, J. B., Loreto, C., Musumeci, G., giuseppina campisi, Lo Muzio, L., Dos Santos, J. N., Pastorino, L., Bufo, P., Pannone, G., Leonardi, R, Matthews, JB, Loreto, C, Musumeci, G, Campisi, G, Lo Muzio, L, dos Santos, JN, Pastorino, L, Bufo, P, and Pannone, G

Subjects
Adult, Male, Histology, Adolescent, Survivin, 6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología [CDU], Settore MED/50 - Scienze Tecniche Mediche Applicate, Apoptosis, Odontogenic Tumors, ß-catenin, NBCCS, Inhibitor of Apoptosis Proteins, Settore MED/29 - Chirurgia Maxillofacciale, Young Adult, Recurrence, Settore MED/28 - Malattie Odontostomatologiche, Humans, beta Catenin, Cell Cycle, NBCCS, ß-catenin, Survivin, KCOT, Basal Cell Nevus Syndrome, Middle Aged, Immunohistochemistry, Gene Expression Regulation, Neoplastic, stomatognathic diseases, KCOT, 2734, Keratins, Female
Abstract

Aim: To determine the epithelial expression of ß-catenin and survivin in sporadic (primary, and recurrent) and nevoid basal cell carcinoma syndrome (NBCCS) keratocystic odontogenic tumour (KCOT) in order to assess activation of the ß-catenin pathway and evidence of apoptotic inhibition, processes that may contribute to the known differences in their biological behaviour. Materials and Methods: Sections from 40 cases of KCOT (19 sporadic/primary; 9 sporadic/recurrent and 12 NBCCS-associated) were immunohistochemically stained for ß-catenin and survivin. The extent and intensity of immunoreactivity within the lining epithelium was assessed, using semi-quantitative scales, independently by two pathologists who were blinded to the clinical-pathological data. Data were analysed using Kruskal-Wallis test and, for pair-wise comparisons, Mann-Whitney test with Bonferroni correction. Results: All cystic epithelial linings stained for ß- catenin and survivin but there were differences in the pattern and intensity of staining among KCOT types. Sporadic primary KCOT showed weaker staining for ß- catenin (P=0.0003) and survivin (P

Published
2013

38. Histopathological pattern of lymph-node metastases from Oral Squamous Cell Carcinoma. An unicentric retrospective study on 146 neck dissections

Author

Contaldo M, FRANCO, Renato, Franco Ionna F, Santoro A, Sbordone C, Longo F, PASQUALI, Daniela, Loreto C, SERPICO, Rosario, Bufo P, Pannone G., Contaldo, M, Franco, Renato, Franco Ionna, F, Santoro, A, Sbordone, C, Longo, F, Pasquali, Daniela, Loreto, C, Serpico, Rosario, Bufo, P, and Pannone, G.

Abstract

Lymph node metastases are responsible for shorter survival in oral squamous cell carcinoma (OSCC). The aim of the present study was to assess the node metastasis frequency and survival according to the node metastasis features in 121 neck dissections (NDs) performed for OSCC, identifying evidence-based correlations and contrasts with previous literature. The retrospective study involved 121 patients affected by OSCC who had undergone modified radical ND (MRND) for therapeutic, elective reasons or after intraoperative positivity to metastasis of sentinel lymph nodes (SLN+). Node metastasis frequency and behaviour (typical vs. atypical) and their number and distribution according to pre-surgical cTNM cancer staging were considered and overall survival Kaplan-Meier curves were calculated for each group in order to compare mortality according to ND type (elective, therapeutic, after SLN+), lymph node metastatic pattern (typical or atypical), size (micrometastasis vs. macrometastasis) and number. Results showed statistically significant different overall survival according to pre-surgical staging, number of lymph nodes harvested and intent to surgery. Sentinel lymph node resulted in the sole positive node affected by metastasis in small cT1- cT2/cN0 OSCC and an ND subsequent to its positivity during intraoperative assessment may be considered an overtreatment.

Published
2013

39. Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 Immunohistochemistry, Consensus PCR HPV-DNA, and In Situ Hybridization.[Identificatico Scopus: 2-s2.0-84857478688]

Author

Pannone G, Rodolico V, Santoro A, Lo Muzio L, Franco R, Botti G, Aquino G, Pedicillo MC, Cagiano S, Campisi G, Rubini C, Papagerakis S, Tornesello ML, Buonaguro FM, Bufo P., DE ROSA, GAETANO, STAIBANO, STEFANIA, Pannone, G, Rodolico, V, Santoro, A, Lo Muzio, L, Franco, R, Botti, G, Aquino, G, Pedicillo, Mc, Cagiano, S, Campisi, G, Rubini, C, Papagerakis, S, DE ROSA, Gaetano, Tornesello, Ml, Buonaguro, Fm, Staibano, Stefania, and Bufo, P.

Subjects
HN-SCC, HPV, Human papillomaviru, Methylation-Specific PCR, OPSCC, DNA consensus PCR, Epigenetic, Head and neck squamous cell carcinoma, OSCC, p16-IHC, Immunohistochemistry, IHC
Abstract

Recent emerging evidences identify Human Papillomavirus (HPV) related Head and Neck squamous cell carcinomas (HN-SCCs) as a separate subgroup among Head and Neck Cancers with different epidemiology, histopathological characteristics, therapeutic response to chemo-radiation treatment and clinical outcome. However, there is not a worldwide consensus on the methods to be used in clinical practice. The endpoint of this study was to demonstrate the reliability of a triple method which combines evaluation of: 1. p16 protein expression by immunohistochemistry (p16-IHC); 2. HPV-DNA genotyping by consensus HPV-DNA PCR methods (Consensus PCR); and 3 viral integration into the host by in situ hybridization method (ISH). This triple method has been applied to HN-SCC originated from oral cavity (OSCC) and oropharynx (OPSCC), the two anatomical sites in which high risk (HR) HPVs have been clearly implicated as etiologic factors. Methylation-Specific PCR (MSP) was performed to study inactivation of p16-CDKN2a locus by epigenetic events. Reliability of multiple methods was measured by Kappa statistics.All the HN-SCCs confirmed HPV positive by PCR and/or ISH were also p16 positive by IHC, with the latter showing a very high level of sensitivity as single test (100\% in both OSCC and OPSCC) but lower specificity level (74\% in OSCC and 93\% in OPSCC).Concordance analysis between ISH and Consensus PCR showed a faint agreement in OPSCC (κ = 0.38) and a moderate agreement in OSCC (κ = 0.44). Furthermore, the addition of double positive score (ISHpositive and Consensus PCR positive) increased significantly the specificity of HR-HPV detection on formalin-fixed paraffin embedded (FFPE) samples (100\% in OSCC and 78.5\% in OPSCC), but reduced the sensitivity (33\% in OSCC and 60\% in OPSCC). The significant reduction of sensitivity by the double method was compensated by a very high sensitivity of p16-IHC detection in the triple approach.Although HR-HPVs detection is of utmost importance in clinical settings for the Head and Neck Cancer patients, there is no consensus on which to consider the 'golden standard' among the numerous detection methods available either as single test or combinations. Until recently, quantitative E6 RNA PCR has been considered the 'golden standard' since it was demonstrated to have very high accuracy level and very high statistical significance associated with prognostic parameters. In contrast, quantitative E6 DNA PCR has proven to have very high level of accuracy but lesser prognostic association with clinical outcome than the HPV E6 oncoprotein RNA PCR. However, although it is theoretically possible to perform quantitative PCR detection methods also on FFPE samples, they reach the maximum of accuracy on fresh frozen tissue. Furthermore, worldwide diagnostic laboratories have not all the same ability to analyze simultaneously both FFPE and fresh tissues with these quantitative molecular detection methods. Therefore, in the current clinical practice a p16-IHC test is considered as sufficient for HPV diagnostic in accordance with the recently published Head and Neck Cancer international guidelines. Although p16-IHC may serve as a good prognostic indicator, our study clearly demonstrated that it is not satisfactory when used exclusively as the only HPV detecting method. Adding ISH, although known as less sensitive than PCR-based detection methods, has the advantage to preserve the morphological context of HPV-DNA signals in FFPE samples and, thus increase the overall specificity of p16/Consensus PCR combination tests.

Published
2012

44. DIFFERENTIAL EXPRESSION OF SURVIVIN IN THYROID CANCER

Author

Pannone G, Bufo P, Santoro A, Zamparese R, Renzullo A, Coppola VR, Accardo G, Bellastella A, PASQUALI, Daniela, Pannone, G, Bufo, P, Santoro, A, Zamparese, R, Renzullo, A, Coppola, Vr, Accardo, G, Bellastella, A, and Pasquali, Daniela

Published
2009

45. Large oral soft tissue metastasis from anaplastic carcinoma of the lung mimicking a primitive malignancy: case report and brief review of the literature

Author

Califano, L., Sanguedolce, F., Staibano, S., Pannone, G., Tortorella, S., Rosario SERPICO, Lo Muzio, L., Bufo, P., Califano, Luigi, Sanguedolce, F, Staibano, Stefania, Pannone, G, Tortorella, S, Serpico, R, Lo Muzio, L, Bufo, P., Califano, L, Staibano, S, Serpico, Rosario, and LO MUZIO, L

Subjects
Diagnosis, Differential, Male, Lung Neoplasms, Carcinoma, Humans, Mouth Neoplasms, Soft Tissue Neoplasms, Middle Aged
Abstract

Metastatic tumours to the oral region are rare, and those reported in the buccal soft tissues are even less frequent. We describe a case of anaplastic carcinoma of the lung in a 60-year-old man, presenting a huge oral metastasis as the first sign of his primitive lung malignancy. Clinically, the oral lesion mimicked a high-grade primitive carcinoma of the oral cavity. The biopsy established the gingival metastasis from lung cancer which was confirmed by a fine-needle aspiration cytology examination. We report an uncommon case of metastatic lung carcinoma to the gingiva emphasizing the differential diagnosis between primary and metastatic tumours; a short discussion on the pathways of metastatization to oral cavity soft tissues, as well as brief review of the literature are also presented.

Published
2008

46. Survivin phosphorylation and M-phase promoting factor in oral carcinogenesis

Author

Pannone, G., Bufo, P., Serpico, R., Rubini, C., Zamparese, R., Corsi, F., Pedicillo, M. C., Staibano, S., Rosa, G., Lorenzo Lo Muzio, Pannone, G, Bufo, P, Serpico, R, Rubini, C, Zamparese, R, Corsi, F, Pedicillo, Mc, Staibano, Stefania, DE ROSA, Gaetano, LO MUZIO, L., Serpico, Rosario, Staibano, S, and DE ROSA, G

Subjects
Male, p-survivin, Survivin, Maturation-Promoting Factor, Cyclin B, p34, Inhibitor of Apoptosis Proteins, Immunoenzyme Techniques, Cyclin-B1, CDC2 Protein Kinase, Biomarkers, Tumor, Humans, cdc2, Cyclin B1, Phosphorylation, Apoptosi, Middle Aged, Neoplasm Proteins, stomatognathic diseases, Carcinoma, Squamous Cell, Female, Mouth Neoplasms, OSCC, Microtubule-Associated Proteins, Precancerous Conditions, MPF
Abstract

Survivin is a recently described inhibitor of apoptosis and mitotic regulator which is selectively over-expressed in human tumors. Its expression rate is predictive of disease progression, early recurrences and resistance to therapy. Up-regulation of survivin in oral pre-malignant lesions (OPL) and in oral squamous cell carcinoma (OSCC) has already been demonstrated in previous studies. A critical step for activation of survivin has been identified in the phosphorylation on Thr34 by the main mitotic kinase p34cdc2-cyclin B1. The aim of this work was to investigate the relationship between survivin, its phosphorylated active form (p-survivin) and M-phase promoting factor (MPF), p34cdc2-cyclin B1 in oral carcinogenesis. 32 OSCCs and 17 OPLs from surgical specimens were studied for cyclin B1, p-survivin, survivin, and p34cdc2 expression by immunohistochemistry. All cases of OSCC expressed survivin and its expression rate was correlated to p-survivin levels (P

Published
2007

49. Surviving mRNA splicing in oral cancer

Author

PANNONE G, BUFO P, SANTARELLI A, LO MUZIO L, DE MARIA S, METAFORA S, BRACA A, CARTEN M, SERPICO R, CAMPISI, Giuseppina, DI LIBERTO C., FARINA, Elvira Vittoria, PANZARELLA, Vera, PANNONE G, BUFO P, SANTARELLI A, LO MUZIO L, DE MARIA S, METAFORA S, BRACA A, CARTEN M, SERPICO R, FARINA E, CAMPISI G, PANZARELLA V, and DI LIBERTO C

Published
2006

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