المؤلفون: Miglietta, F., Iannaccone, D., Griguolo, G., Giarratano, T., Porra, F., Cacciatore, M., Cappellesso, R., Girardi, F., Bottosso, M., Crema, A., Vernaci, G., Giorgi, C.A., Zurlo, C., Fassan, M., Guarneri, V., Dieci, M.V.

المصدر: ESMO Open ; volume 8, issue 1, page 101400 ; ISSN 2059-7029

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.esmoop.2023.101400Test
https://api.elsevier.com/content/article/PII:S2059702923006269?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2059702923006269?httpAccept=text/plainTest

المؤلفون: Coati, I, Lotz, G, Fanelli, GN, Brignola, S, Lanza, C, Cappellesso, R, Pellino, A, Pucciarelli, S, Spolverato, G, Guzzardo, V, Munari, G, Zaninotto, G, Scarpa, M, Mastracci, L, Farinati, F, Realdon, S, Pilati, P, Lonardi, S, Valeri, N, Rugge, M, Kiss, A, Loupakis, F, Fassan, M

المساهمون: Valeri, Nicola

مصطلحات موضوعية: Adenocarcinoma, Adult, Aged, 80 and over, Claudins, Female, Humans, Male, Middle Aged, RNA, Viral, Stomach Neoplasms, Tissue Array Analysis

جغرافية الموضوع: England

الوصف: BACKGROUND: Claudin-18 (CLDN18) is a highly specific tight junction protein of the gastric mucosa. An isoform of CLDN18, the Claudin 18.2, has recently emerged as an innovative drug target for metastatic gastric cancer. METHODS: We investigated the immunohistochemical profile of CLDN18, p53, p16, E-cadherin, MSH2, MSH6, MLH1, PSM2, HER2, and PDL-1 in a large series of 523 primary gastric carcinomas (GCs; n = 408) and gastro-oesophageal carcinomas (GECs; n = 115) and 135 matched and synchronous nodal metastases. The status of HER2 and EBER by means of chromogenic in situ hybridisation (CISH) was also evaluated. RESULTS: High membranous CLDN18 expression was present in 150/510 (29.4%) primary cases and in 45/132 (34.1%) metastases. An abnormal expression (i.e. nuclear and/or cytoplasmic) was observed in 115 (22.5%) primary cases and in 33 (25.0%) metastases. A 38.8% of the cases showed significant CLDN18 intratumoural variability among the different tissue microarray cores obtained from the same tumour. Positive membrane CLDN18 expression was statistically associated with non-antral GCs (p = 0.016), Lauren diffuse type (p = 0.009), and with EBV-associated cancers (p < 0.001). CONCLUSIONS: CLDN18 is frequently expressed in gastric and gastro-oesophageal cancers; further studies should investigate the prognostic significance of CLDN18 heterogeneity in order to implement its test into clinical practice.

وصف الملف: Print-Electronic; 263; application/pdf

العلاقة: British Journal of Cancer, 2019, 121 (3), pp. 257 - 263; https://repository.icr.ac.uk/handle/internal/5373Test

الإتاحة: https://doi.org/10.1038/s41416-019-0508-4Test
https://repository.icr.ac.uk/handle/internal/5373Test

المؤلفون: Cappellesso R., Nozzoli F., Marino F. Z., Simi S., Castiglione F., De Giorgi V., Cota C., Senetta R., Scognamiglio G., Anniciello A. M., Cesinaro A. M., Mandala M., Gianatti A., Valente M. G., Valeri B., Sementa A. R., Ricci C., Corti B., Roviello G., Dei Tos A. P., Franco R., Massi D.

المساهمون: Cappellesso R., Nozzoli F., Marino F.Z., Simi S., Castiglione F., De Giorgi V., Cota C., Senetta R., Scognamiglio G., Anniciello A.M., Cesinaro A.M., Mandala M., Gianatti A., Valente M.G., Valeri B., Sementa A.R., Ricci C., Corti B., Roviello G., Dei Tos A.P., Franco R., Massi D.

مصطلحات موضوعية: Atypical spitz tumor, NTRK, NTRK1, NTRK3, Pan-TRK, Adolescent, Adult, Child, Preschool, Data Accuracy, Female, High-Throughput Nucleotide Sequencing, Human, Immunohistochemistry, In Situ Hybridization, Fluorescence, Male, Middle Aged, Nevus, Epithelioid and Spindle Cell, Oncogene Proteins, Fusion, Real-Time Polymerase Chain Reaction, Receptor, trkA, trkC, Sequence Analysis, RNA, Skin Neoplasm, Young Adult

الوصف: Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs NTRK1 fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of NTRK1 compared to NTRK3 alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of NTRK fusions may require the use of different molecular techniques.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34830218; info:eu-repo/semantics/altIdentifier/wos/WOS:000727343900001; volume:22; issue:22; firstpage:12332; lastpage:12332; numberofpages:1; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/2318/1858947Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85118978430

الإتاحة: https://doi.org/10.3390/ijms222212332Test
http://hdl.handle.net/2318/1858947Test

المؤلفون: Rastrelli M., Del Fiore P., Russo I., Tartaglia J., Dal Monico A., Cappellesso R., Nicole L., Piccin L., Fabozzi A., Biffoli B., Di Prata C., Ferrazzi B., Dall'Olmo L., Vecchiato A., Spina R., Russano F., Bezzon E., Cingarlini S., Mazzarotto R., Parisi A., Scarzello G., Pigozzo J., Brambullo T., Tropea S., Vindigni V., Bassetto F., Bertin D., Gregianin M., Dei Tos A. P., Cavallin F., Alaibac M., Chiarion-Sileni V., Mocellin S.

المساهمون: Rastrelli, M., Del Fiore, P., Russo, I., Tartaglia, J., Dal Monico, A., Cappellesso, R., Nicole, L., Piccin, L., Fabozzi, A., Biffoli, B., Di Prata, C., Ferrazzi, B., Dall'Olmo, L., Vecchiato, A., Spina, R., Russano, F., Bezzon, E., Cingarlini, S., Mazzarotto, R., Parisi, A., Scarzello, G., Pigozzo, J., Brambullo, T., Tropea, S., Vindigni, V., Bassetto, F., Bertin, D., Gregianin, M., Dei Tos, A. P., Cavallin, F., Alaibac, M., Chiarion-Sileni, V., Mocellin, S.

مصطلحات موضوعية: Merkel carcinoma, Merkel cell cancer, Merkel treatment strategie, non-melanoma skin cancer (NMSC), skin cancer

الوصف: Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC. Methods: A retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens. Results: 143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor. Conclusions: Autoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34976795; info:eu-repo/semantics/altIdentifier/wos/WOS:000738466200001; volume:11; firstpage:737842; numberofpages:10; journal:FRONTIERS IN ONCOLOGY; http://hdl.handle.net/11577/3410860Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85122104340; https://zenodo.org/record/5833513#.YdwgsVnSKUkTest

الإتاحة: https://doi.org/10.3389/fonc.2021.737842Test
http://hdl.handle.net/11577/3410860Test
https://zenodo.org/record/5833513#.YdwgsVnSKUkTest

المؤلفون: Franz L, Nicolè L, Frigo AC, Ottaviano G, Gaudioso P, Saccardo T, Visconti F, Cappellesso R, Blandamura S, Fassina A, Marioni G

المساهمون: Franz, L, Nicolè, L, Frigo, Ac, Ottaviano, G, Gaudioso, P, Saccardo, T, Visconti, F, Cappellesso, R, Blandamura, S, Fassina, A, Marioni, G

مصطلحات موضوعية: laryngeal squamous cell carcinoma, epithelial–mesenchymal transition, N-cadherin, Slug, angiogenesi, CD105, prognosis

الوصف: The mechanism of epithelial–mesenchymal transition (EMT) is fundamental for carcinogenesis, tumor progression, cancer cell invasion, metastasis, recurrence, and therapy resistance, com-prising important events, such as cellular junction degradation, downregulation of epithelial phenotype markers, overexpression of mesenchymal markers, and increase in cellular motility. The same factors that drive epithelial cells toward a mesenchymal phenotype may also drive endothelial cells toward a proangiogenic phenotype. The aim of this exploratory study was to investigate a potential interplay between EMT and angiogenesis (quantified through CD105 ex-pression) in laryngeal carcinoma (LSCC). CD105-assessed microvessel density (MVD) and EMT markers (E-cadherin, N-cadherin, Snail, Slug, Zeb1, and Zeb2) were assessed on 37 consecutive LSCC cases. The univariate Cox regression model identified pN+ status (p = 0.0343) and Slug ex-pression (p = 0.0268) as predictive of disease-free survival (DFS). A trend toward significance emerged for CD105-assessed MVD (p = 0.0869) and N-cadherin expression (p = 0.0911). In the multivariate Cox model, pN-status, Slug, and N-cadherin expressions retained their significant values in predicting DFS (p = 0.0346, p = 0.0430, and p = 0.0214, respectively). Our data support the hypothesis of a mutual concurrence of EMT and angiogenesis in driving LSCC cells toward an aggressive phenotype. To better characterize the predictive performance of prognostic models based on EMT and angiogenesis, further large-scale prospective studies are required.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000671606300001; volume:13; firstpage:3339; journal:CANCERS; http://hdl.handle.net/11577/3394526Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85111789717

الإتاحة: https://doi.org/10.3390/cancers13133339Test
http://hdl.handle.net/11577/3394526Test

المؤلفون: Nicolè L, Sarcognato S, Cappellesso R, SANAVIA T, Luchini C, Mescoli C, Capelli P, Fassina A, Guido M

المساهمون: Nicolè L, Sarcognato S, Cappellesso R, SANAVIA T, Luchini C, Mescoli C, Capelli P, Fassina A, Guido M

الوصف: Background & Objectives: Differential diagnosis between intrahepatic cholangiocarcinoma (ICC), an aggressive liver tumour, and bile duct adenoma (BDA), an indolent lesion, is fundamental but sometimes challenging, particularly for well-differentiated ICC. Morphological analysis alone is often not sufficient to achieve a correct diagnosis. Several immunohistochemical markers have been proposed to improve the diagnostic performance, but all of them, taken singularly, showed low sensitivity and are not used in clinical practice. Moreover, only a few studies focused on the differential diagnosis between ICC and BDA, so far. The aim of this study was to investigate the diagnostic performance of a 3-marker panel, including p53, p16INK4a, and S100P, to evaluate whether their combination might help to distinguish ICC from BDA. Methods: Fifty-two surgically resected liver nodules (30 ICCs and 22 BDAs) were retrospectively selected and stained with p53, p16INK4a, and S100P. p53 was considered positive when a strong nuclear immunoreaction was observed, while p16INK4a and S100P positivity was both nuclear and cytoplasmic. An algorithm was built and its diagnostic performance analysed. Results: As expected, despite their perfect specificity (100%), all the evaluated markers showed a low sensitivity when considered singularly (56.7%, 26.6%, 23.4%, for p53, p16INK4a, S100P, respectively). On the contrary, the algorithm based on the sequential use of p53, p16INK4a, and S100P, showed a sensitivity of 73.4%, a specificity of 100% and an overall accuracy of 84.6%. Conclusion: The adopted 3-marker algorithm is helpful in differentiating ICC from BDA. Further larger studies are needed to validate the proposed algorithm.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000483546903184; 31st European Congress of Pathology; volume:475; firstpage:S220; lastpage:S220; numberofpages:1; journal:VIRCHOWS ARCHIV; http://hdl.handle.net/2318/1806499Test

الإتاحة: http://hdl.handle.net/2318/1806499Test

المؤلفون: Iafrate M., Motterle G., Zaborra C., Leone N., Prayer-Galetti T., Zattoni F., Guttilla A., Cappellesso R., Dei Tos AP, Rossi C. R., Del Fiore P., Rastrelli M., Mocellin S.

المساهمون: Iafrate, M., Motterle, G., Zaborra, C., Leone, N., Prayer-Galetti, T., Zattoni, F., Guttilla, A., Cappellesso, R., DEI TOS, Angelo, Rossi, C. R., Del Fiore, P., Rastrelli, M., Mocellin, S.

مصطلحات موضوعية: paratesticular sarcoma, soft tissue sarcoma, spermatic cord, spermatic cord sarcoma, treatment, urologic sarcoma

الوصف: Introduction: Spermatic cord sarcomas represent a rare genitourinary malignancy with a challenging diagnostic and therapeutic pathway. Different histotypes have been described and prognostic factors remain poorly defined due to the paucity of data presented in literature. Methods: Retrospective chart review of 22 adult patients treated for spermatic cord sarcoma in a single institution in the last 20 years was performed. Clinicopathological characteristics of the tumors were collected with primary and subsequent treatment. Survival analysis was performed in order to identify prognostic factors of disease-specific survival. Results: The median age at diagnosis was 68 years (58–78), the most common histotype was liposarcoma (14/22), and most patients (63.6%) were found to have positive surgical margins after surgery. The 5-year cancer specific survival was 91.3%. Grading (p = 0.480), histotype (p = 0.327), and type of intervention (p = 0.732) were not associated with survival. All patients dead of disease had positive surgical margins (p = 0.172). Conclusion: We report a good prognosis at 5 years. Wide radical resection remains the first and probably the most important step; thus, according also to literature, negative surgical margins should be aimed.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33282904; info:eu-repo/semantics/altIdentifier/wos/WOS:000594440600001; volume:7; firstpage:566408; journal:FRONTIERS IN SURGERY; http://hdl.handle.net/11577/3361882Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85097072242

الإتاحة: https://doi.org/10.3389/fsurg.2020.566408Test
http://hdl.handle.net/11577/3361882Test

المؤلفون: El Bairi K., Haynes H. R., Blackley E., Fineberg S., Shear J., Turner S., de Freitas J. R., Sur D., Amendola L. C., Gharib M., Kallala A., Arun I., Azmoudeh-Ardalan F., Fujimoto L., Sua L. F., Liu S. -W., Lien H. -C., Kirtani P., Balancin M., El Attar H., Guleria P., Yang W., Shash E., Chen I. -C., Bautista V., Do Prado Moura J. F., Rapoport B. L., Castaneda C., Spengler E., Acosta-Haab G., Frahm I., Sanchez J., Castillo M., Bouchmaa N., Md Zin R. R., Shui R., Onyuma T., Husain Z., Willard-Gallo K., Coosemans A., Perez E. A., Provenzano E., Ericsson P. G., Richardet E., Mehrotra R., Sarancone S., Ehinger A., Rimm D. L., Bartlett J. M. S., Viale G., Denkert C., Hida A. I., Sotiriou C., Loibl S., Hewitt S. M., Badve S., Symmans W. F., Kim R. S., Pruneri G., Goel S., Francis P. A., Inurrigarro G., Yamaguchi R., Garcia-Rivello H., Horlings H., Afqir S., Salgado R., Adams S., Kok M., Dieci M. V., Michiels S., Demaria S., Loi S., Schelfhout V., Arbzadeh E., Bondanar A., Reyes S. A. G., Ruz J. R., Kang J., Xiang L., Zimovjanova M., Togores P., Ozturk T., Patil A., Corpa M., Whitehouse A., Tan B., de Paula A., Rossetti C., Lang-Schwarz C., Mahon S., Giacometti C., Linderholm B., Deman F., Montagna G., Gong G., Pavcovich M., Chaer Y., Cabrero I. A., de Brito M. L., Ilieva N., Fulop A., Souza M., Bilancia D., Idowu M., Johri R., Szpor J., Bachani L., Schmitt F., Giannotti M., Kurebayashi Y., Ramirez B. E. A., Salido E., Bortesi L., Bonetto S., Elomina K., Lopez P., Sharma V., Edirisinghe A., Mathur D., Sahay A., Mouloud M. A., Giang C. H., Mukolwe E., Kiruka E., Samberg N., Abe N., Brown M., Millar E., Li X. B., Yuan Z., Pasupathy A., Miele R., Luff R., e Porfirio M. M. A., Ajemba O., Soni R., Orvieto E., DiMaio M., Thomas J., Merard R., Subramaniam M. M., Apolinario T., Preda O., Preda R., Makanga A., Maior M. S., Li L., Saghatchian M., Saurine T., Janssen E., Cochran J., Vlada N., Cappellesso R., Elfer K., Hollick M., Desai S., Oner G., Schreurs A., Liu S., Perera R., Mercurio P., Garcia F., Hosny K., Matsumoto H., van Deurzen C., Bianchini G., Coban I., Jahangir A., Rahman A., Stover D., Luz P., Martel A., Waumans Y., Stenzinger A., Cortes J., Dimitrova P., Nauwelaers I., Velasco M., Fan F., Akturk G., Firer M., Roxanis I., Schneck M., Wen H., Cockenpot V., Konstantinov A., Calatrava A., Vidya M. N., Choi H. J., Jank P., CIinen A. H., Sabanathan D., Floris G., Hoeflmayer D., Hamada T., Laudus N., Grigoriadis A., Porcellato I., Acs B., Miglietta F., Parrodi J., Clunie D., Calhoun B., Lu F. -I., Lefevre A., Tabbarah S., Tran W., Garcia-murillas I., Jelinic P., Boeckx C., Souza S., Cebollero M. C., Felip E., Rendon J. L. S., El Gabry E., Saltz J., Bria E., Garufi G., Hartman J., Sebastian M., Olofsson H., Kooreman L., Cucherousset J., Mathieu M. -C., Ballesteros-Merino C., Siziopikou P., Fong J., Klein M., Qulis I. R. I., Wesseling J., Bellolio E., Araya J. C., Naber S., Cheang M., Castellano I., Ales A., Laenkholm A. -V., Kulka J., Quinn C., Sapino A., Amendoeira I., Marchio' C., Braybrooke J., Vincent-Salomon A., Korski K. P., Sofopoulos M., Stovgaard E. I. S., Bianchi S., Bago-Horvath Z., Yu C., Regitnig P., Hall S., Kos Z., Sant S., Tille J. -C., Gallas B., Bethmann D., Savas P., Mendes L., Soler T., van Seijen M., Gruosso T., Quintana A., Giltnane J., Van den Eynden G., Duregon E., de Cabo R., Recamo P. C., Gaboury L., Zimmerman J., Pop C. S., Wernicke A., Williams D., Gill A., Solomon B., Thapa B., Farshid G., Gilham L., Christie M., O'Toole S., Hendry S., Fox S. B., Luen S. J., Lakhani S. R., Fuchs T., John T., Brcic I., Hainfellner J., Sigurd L., Preusser M., Poortmans P., Decaluwe A., Carey C., Colpaert C., Larsimont D., Peeters D., Broeckx G., van de Vijver K., Buisseret L., Dirix L., Hertoghs M., Piccart M., Ignatiadis M., Van Bockstal M., Sirtaine N., Vermeulen P., de Wind R., Declercq S., Gevaert T., Haibe-Kans B., Nelson B. H., Watson P. H., Leung S., Nielsen T., Shi L., Balslev E., Thagaard J., Almangush A., Makitie A., Joensuu H., Lundin J., Drubay D., Roblin E., Andre F., Penault-Llorca F., Lemonnier J., Adam J., Lacroix-Triki M., Ternes N., Radosevic-Robin N., Klaushen F., Weber K., Harbeck N., Gluz O., Wienert S., Cserni G., Vingiani A., Criscitiello C., Solinas C., Curigliano G., Konishi E., Suzuki E., Yoshikawa K., Kawaguchi K., Takada M., Toi M., Ishida M., Shibata N., Saji S., Kogawa T., Sakatani T., Okamoto T., Moriya T., Kataoka T., Shimoi T., Sugie T., Mukohara T., Shu Y., Kikawa Y., Kozuka Y., Sayed S., Rahayu R., Ramsaroop R., Senkus-Konefka E., Chmielik E., Cardoso F., Ribeiro J., Chan J., Dent R., Martin M., Hagen C., Guerrero A., Rojo F., Comerma L., Nuciforo P., Serrano V. V., Camaea V. P., Steenbruggen T., Ciompi F., Nederlof I., Jan Hudecek, van der Laak J., van den Berg J., Voorwerk L., van de Vijver M., de Maaker M., Linn S., McKenzie H., Somaiah N., Tutt A., Swanton C., Hiley C., Moore D. A., Hall J. A., Le Quesne J., Jabbar K. A., al Bakir M., Hills R., Irshad S., Yuan Y., Li Z., Liu M., Klein J., Fadare O., Thompson A., Lazar A. J., Gown A., Lo A., Garrido Castro A. C., Madabhushi A., Moreira A., Richardson A., Beck A. H., Bellizzi A. M., Wolff A., Harbhajanka A., Sharma A., Cimino-Mathews A., Srinivasan A., Singh B., Chennubhotla C. S., Chauhan C., Dillon D. A., Zardavas D., Johnson D. B., Thompson A. E., Brogi E., Reisenbichler E., Huang E., Hirsch F. R., McArthur H., Ziai J., Brock J., Kerner J., Zha J., Lennerz J. K., Carter J. M., Reis-Filho J., Sparano J., Balko J. M., Pogue-Geile K., Steele K. E., Blenman K. R. M., Allison K. H., Pusztai L., Cooper L., Estrada V. M., Flowers M., Robson M., Rebelatto M. C., Hanna M. G., Goetz M. P., Khojasteh M., Sanders M. E., Regan M. M., Misialek M., Amgad M., Tung N., Singh R., Huang R., Pierce R. H., Leon-Ferre R., Swain S., Ely S., Kim S. -R., Bedri S., Paik S., Schnitt S., d'Alfons T., Kurkure U., Bossuyt V., Tong W., Wang Y., Dos Anjos C. H., Gaire F., Van Diest P. J.

المساهمون: El Bairi K., Haynes H.R., Blackley E., Fineberg S., Shear J., Turner S., de Freitas J.R., Sur D., Amendola L.C., Gharib M., Kallala A., Arun I., Azmoudeh-Ardalan F., Fujimoto L., Sua L.F., Liu S.-W., Lien H.-C., Kirtani P., Balancin M., El Attar H., Guleria P., Yang W., Shash E., Chen I.-C., Bautista V., Do Prado Moura J.F., Rapoport B.L., Castaneda C., Spengler E., Acosta-Haab G., Frahm I., Sanchez J., Castillo M., Bouchmaa N., Md Zin R.R., Shui R., Onyuma T., Husain Z., Willard-Gallo K., Coosemans A., Perez E.A., Provenzano E., Ericsson P.G., Richardet E., Mehrotra R., Sarancone S., Ehinger A., Rimm D.L., Bartlett J.M.S., Viale G., Denkert C., Hida A.I., Sotiriou C., Loibl S., Hewitt S.M., Badve S., Symmans W.F., Kim R.S., Pruneri G., Goel S., Francis P.A., Inurrigarro G., Yamaguchi R., Garcia-Rivello H., Horlings H., Afqir S., Salgado R., Adams S., Kok M., Dieci M.V., Michiels S., Demaria S., Loi S.

الوصف: The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34853355; info:eu-repo/semantics/altIdentifier/wos/WOS:000724789500001; volume:7; issue:1; firstpage:150; lastpage:166; numberofpages:17; journal:NPJ BREAST CANCER; http://hdl.handle.net/2318/1861060Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85120908291; https://www.nature.com/articles/s41523-021-00346-1Test

الإتاحة: https://doi.org/10.1038/s41523-021-00346-1Test
http://hdl.handle.net/2318/1861060Test
https://www.nature.com/articles/s41523-021-00346-1Test

المؤلفون: Nicolè L, Sanavia T, Cappellesso R, Fassina A

المساهمون: Nicolè L, Sanavia T, Cappellesso R, Fassina A

الوصف: Objective. Necroptosis (NPC) is a form of programmed cell death that culminates with the rupture of the cell membrane followed by the releasing of cellular elements. Evidence showed that tumors with high expression of NCP-related genes are associated with high cytotoxic CD8+ T-cell infiltrates, mediated by signaling from Dendritic (DC) and CD4+ T-cells. This study shows a pan-cancer view of the relationship between NCP and immune infiltration and their prognostic relevance across 24 cancer types from The Cancer Genome Atlas (TCGA). Materials and methods. Gene expression RNA-seq data from 5,451 primary solid tumors were considered, excluding cases with treatments before surgery and with residual tumor. A deconvolution algorithm was used to estimate the level of tumor-infiltrating immune cells in each RNA- seq sample, considering the populations: B-cells, CD4 T-cells, CD8 Tcells, Macrophages and DC. For each immune population, the relative infiltration score was dichotomized at low and high infiltration using the 25th and 75h percentiles, respectively. Logistic regression and likelihood ratio test were applied to 163 genes belonging to Necroptosis pathway from KEGG database to test whether they are significantly associated to the infiltration of a specific immune population. FDR-adjusted p-values <0.05 were considered statistically significant. The prognostic relevance of the NCP genes significantly correlated with the infiltration was evaluated by Cox regression and log-rank test. Results. DC and CD4+ T-cells showed the highest number of cancer types (8) reporting more than half genes of NCP pathway significantly correlated with their infiltration. CD8+ T-cell infiltration correlated with >50% of NCP genes in 5 of these 8 cancer types: Kidney-Renal, Breast, Prostate, Pancreatic and Thyroid tumors. DC also showed the highest number of NCP genes (69) correlated with their infiltration in more than half of the analyzed cancer types, including the main genes involved in NCP execution: RIPK1, RIPK3, MLKL and ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30546142; ispartofbook:Proceedings: Congresso Annaule di Anatomia Patologica SIAPEC-IAP 2018; Congresso Annuale di Anatomia Patologica (SIAPEC-IAP); volume:110; issue:3; firstpage:207; lastpage:207; numberofpages:1; journal:PATHOLOGICA; http://hdl.handle.net/2318/1806028Test; http://www.pathologica.it/wp-content/uploads/2018/10/Pathologica_3_18-1.pdfTest

الإتاحة: http://hdl.handle.net/2318/1806028Test
http://www.pathologica.it/wp-content/uploads/2018/10/Pathologica_3_18-1.pdfTest

المؤلفون: Hench J., Mihic-Probst D., Agaimy A., Frank S., Meyer P., Hultschig C., Simi S., Alos L., Balamurugan T., Blokx W., Bosisio F., Cappellesso R., Griewank K., Hadaschik E., van Kempen L. C., Kempf W., Lentini M., Mazzucchelli L., Rinaldi G., Rutkowski P., Schadendorf D., Schilling B., Szumera-Cieckiewicz A., van den Oord J., Mandala' M., Massi D.

المساهمون: Hench, J., Mihic-Probst, D., Agaimy, A., Frank, S., Meyer, P., Hultschig, C., Simi, S., Alos, L., Balamurugan, T., Blokx, W., Bosisio, F., Cappellesso, R., Griewank, K., Hadaschik, E., van Kempen, L. C., Kempf, W., Lentini, M., Mazzucchelli, L., Rinaldi, G., Rutkowski, P., Schadendorf, D., Schilling, B., Szumera-Cieckiewicz, A., van den Oord, J., Mandala', M., Massi, D.

مصطلحات موضوعية: Copy number profiling, Dedifferentiated melanoma, DNA methylation, Epigenetics

الوصف: Purpose: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases. Patients and methods: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out. Results: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome. Conclusions: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37098294; info:eu-repo/semantics/altIdentifier/wos/WOS:000994344000001; volume:187; firstpage:7; lastpage:14; numberofpages:8; journal:EUROPEAN JOURNAL OF CANCER; https://hdl.handle.net/11391/1566824Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85152888061

الإتاحة: https://doi.org/10.1016/j.ejca.2023.03.032Test
https://hdl.handle.net/11391/1566824Test