Anatomia Patologica

 Attività

La Struttura Complessa di Anatomia Istologia Patologica e Citodiagnostica fa parte del Dipartimento di Prevenzione e Diagnostica Oncologica dell’Istituto Nazionale Tumori “Regina Elena”.
Svolge attività a carattere diagnostico clinico-assistenziale e di ricerca scientifica biomedica in ambito oncologico e collabora alla prevenzione oncologica, nel definire fattori di rischio tumorale e alla pianificazione terapeutica in ambito oncologico, nel definire fattori prognostici e predittivi delle principali neoplasie umane.

L' Unità Operativa impiega le tecnologie più aggiornate ed affidabili per efficienza ed efficacia, adotta la migliore organizzazione procedurale interna con il coinvolgimento di tutto il personale, favorisce l’integrazione dell’attività clinica con la ricerca scientifica e  il massimo rispetto delle procedure operative.
L' attività di ricerca scientifica, in accordo alla politica della qualità, si concretizza anche attraverso collaborazioni con altre istituzioni nazionali e internazionali, al fine di promuovere le conoscenze avanzate nel settore oncologico.
La struttura è certificata UNI/EN/ISO 9001.

 Collaboratori

Personale Tecnico
Sig.ra Paola Canalini (coordinatore)
Tel. 06 52666917

Dr.ssa Beatrice Casini

Tel. 06 52666828

Sig.ra Stefania Filippi
Tel. 06 52666828

Sig.ra Angela Maria Lattanzi
Tel. 06 52666828

Sig.ra Eliana Pallottini

Tel. 06 52666828

Sig.ra Patrizia Palmarelli
Tel. 06 52666828

Sig.ra Chiara Paolemili
Tel. 06 52666828

Sig.ra Arianna Papadantonakis

Tel. 06 52666828

Sig.ra Annarita Pennetti
Tel. 06 52666828
 
Sig.ra Patrizia Scordati
Tel. 06 52666828

Sig.ra Annamaria Tirabassi

Tel. 06 52666828 

 Contrattisti di ricerca

Dott.ssa Cristiana Ercolani
(Biologa)
Metodologie applicate: mutazioni geniche mediante sequenziamento; Multiplex Ligationdependent Probe Amplification (MLPA) su carcinoma mammario e gastrico, con elaborazione dei dati ottenuti.
 
Dott.ssa Elisa Melucci
(Biologa)
Metodologie applicate: mutazioni geniche mediante sequenziamento diretto, real time PCR e analisi dei frammenti su carcinoma del colon e del polmone, con elaborazione dei dati ottenuti.
 
Sig.ra Barbara Antoniani
(Tecnico di laboratorio biomedico)
Taglio al microtomo e al criostato, gestione della biobanca tessuti congelati, allestimento di Tissue Micro Array,
 
Sig. Robert Martucci
(Collaboratore tecnico informatico)
Gestione del programma di refertazione Winsap ; inserimento ed estrapolazioni dati a fini amministrativi; archivio dei preparati istologici e citologic ; gestione e implementa mento data base di timomi e linfomi.
 
Frequentatori per elaborazione tesi di laurea specialistica in Scienze Biologiche

Dott. Valerio D’Alicandro
 
Argomento della tesi: “Studio di alterazioni molecolari predittive di risposta a terapia nel carcinoma del polmone”. Mutazioni geniche mediante sequenziamento diretto e real time PCR.

Dott.ssa Valentina Dimartino
 
Argomento della tesi: “Perdita di eterozigosità del gene EGFR in carcinomi della mammella tripli negativi”. Mutazioni geniche mediante sequenziamento diretto, real time PCR e analisi dei frammenti. 

 Visite / esami

L’ attività diagnostica clinico-assistenziale della Unità Operativa si articola in sintesi come segue:

Diagnostica istopatologica 
compresa la diagnostica istopatologica intra-operatoria (esami istologici estemporanei intra-operatori.

Diagnostica citologica
compresa la citologia cervico-vaginale

Diagnostica molecolare

Riscontri diagnostici necroscopici
autopsie

Attività di consulenza
  

Ambulatorio Citologia Agoaspirativa:
Esecuzione di agoaspirati di organi/lesioni superficiali, quali mammella e linfonodi superficiali (prelievo e diagnosi).

Ambulatorio Citologia Esfoliativa:
Prelievo di cellule della cervice uterina per identificazione e caratterizzazione genotipica di HPV.

 Dove siamo/Modalità di accesso

Orario di apertura al pubblico:

Dal Lunedì al Venerdì, dalle ore 8.30 alle ore 11.00

I prelievi cervico-vaginali per ricerca HPV saranno effettuati presso l'HPV Unit, nelle giornate di lunedì e venerdì dalle ore 09.00 alle ore 12.00 con prenotazione al numero 06 52665980.

I prelievi agoaspirati gli stessi potranno essere effettuati esclusivamente su indicazione del Medico IFO, secondo la sede topografica della lesione presso gli ambulatori chirurgici interessati.

 Ritiro Referti

- I referti ambulatoriali si ritirano presso gli AMBULATORI GENERALI  al piano zero HALL PRINCIPALE , dalle ore 8.30 alle ore 13.00 dal lunedì al venerdì.

 

- Presso la UOC di Anatomia Patologica  si ritirano i referti dell’attività libero professionale intramoenia (ALPI) dalle ore 8.30 alle ore 11.00  dal lunedì al venerdì.

 Progetti ricerca

La UOC di Anatomia Patologica è attiva in diversi settori della ricerca biomedica in ambito oncologico, con particolare riguardo al carcinoma della mammella (breast cancer), al carcinoma del polmone (lung cancer), al carcinoma del colon-retto (colorectal cancer), alle patologie HPV correlate (HPV related diseases), alle neoplasie epiteliali del timo (thymic epithelial tumours), al melanoma, alle neoplasie della regione testa/collo, alle neoplasie dello scheletro e dei tessuti molli, alle neoplasie dell’ apparato urogenitale, e alle neoplasie del sistema nervoso centrale.
I principali argomenti di ricerca sono di seguito riportati (in lingua inglese), con particolare riferimento all’ attività svolta nel biennio 2011-2012 e agli obiettivi per l’ anno 2013 :
Breast Cancer (BC) 1.  In collaboration with the Translational Oncogenomic Laby/IRE, we showed that microRNA-10b_ is a master regulator of BC cell proliferation and is downregulated in tumoral samples versus matched peritumoral counterparts. In particular, we identified and validated in vivo by immunohistochemistry three novel target mRNAs of miR-10b_ (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in BC patients is associated with reduced survival.2. We evaluated the association between the immunohistochemical expression of Phospholipase Cc1 (PLCc1) together with its phosphorilated forms with the clinical outcome of node negative BC patients. PLCc1, PLCc1-pY1253 and PLCc1-pY783 protein expression were assessed on tissue microarrays analyzing two study groups. The first consisted of 292 (training set) and the second of 122 (validation set) early BC. High expression of PLCc1, and of its activated forms, is associated with a worse clinical outcome in terms of distant metastases, and not of local relapse.3. In collaboration with Prof A. Weisz, University of Salerno, we evidenced that  the nuclear receptors ERα and ERβ, display functional antagonism with each other, with ERβ acting as oncosuppressor and interfering with the effects of ERα on cell proliferation and tumor progression. Indeed, hormone-responsive, ERα+ BC cells often lack ERβ, which is frequently associated to a less aggressive tumor phenotype. The expression pattern of 67 miRNAs, including 10 regulated by ERβ, clearly distinguishes N0 ERβ+, from N+ ERβ BC. In particular, ERβ downregulates miR-30a and promotes miR-23b, -27b and 24-1 cell accumulation These results indicate that cell autonomous regulation of miRNA expression is part of the mechanism of action of ERβ in BC c and could contribute to establishment or maintenance of a less aggressive tumor phenotype mediated by this nuclear receptor.4. We evaluated whether multiplex ligation-dependent probe amplification (MLPA)  can identify misleading results  in a series of 86 randomly selected BC with known HER2 status focusing on the 40 cases defined as equivocal (HER2 gene copy number 4.0-6.0) and polysomic (≥3 signals/nucleus) by SISH. A high concordance  was found between IHC, SISH and MLPA both in the 14 Non Amplified (NA) cases scoring 0/1+, and in the 19 Amplified (A) cases scoring 3+  by IHC (K=0.94, p<0.0001).. We foundl 4 cases Non Amplified  by SISH and Amplified  by MLPA. All these cases were denoted as “polysomic” by SISH and displayed gain/amplification of the centromeric region. In our series of 86 BC we found  a high concordance rate  (94%) between SISH and MLPA confirming that this method is accurate to detect HER2 gene amplification. Moreover,  we evidenced a variable pattern of gaines and losses of Chr17 genes and none of our cases, as already reported, showed a true  Chr17 polysomy by MLPA. 5. In our Department we validated the molecular diagnostic tool OSNA (One Step Nuclear Acid Amplification.) for the intra-operative analysis of BC metastases in sentinel lymph nodes (SLN).  Multiple Corresponce Analysis and logistic regression evidenced that positive axillary lymph node dissection was significantly associated with a higher cytokeratin (CK) 19 mRNA copy number (>5000; p<0.0001), HER2 subtype (p=0.007) and lymphovascular invasion (p<0.0001). Conversely, BC patients with CK 19 mRNA copy number <2000 mostly presented a luminal subtype and a negative axillary lymph node dissection. We confirmed that OSNA assay can provide standardized and reproducible results and that it represents a fast and quantitative tool for intraoperative evaluation of sentinel lymph node. 2013 proposal:. We will further study miRNA profiles on a larger series of patients with known follow-up, in order to better understand their potential clinical value, focusing on patients developing a metachronous controlateral cancer. Furthermore we aimed to analyze the role of  (PLCc1) together with its phosphorilated forms in a large series of node positive BC. Concerning OSNA assay, our aim will be to validate in a larger and prospective series of BC that omission of axillary lymph node dissection may be proposed in patients presenting a sentinel lymph node with a CK19 mRNA copy number <2000 and a Luminal tumor phenotype. Furthermore, we will validate MLPA as a method of particular clinical relevance in HER2 score 2+ BC in which an increased number of Chr17 centromere signals by ISH may provide misleading HER2 status assessment lowering the number of BC patients who can experience great benefit by trastuzumab or any novel anti HER2 molecule.
Colorectal Cancer (CRC).1. Starting from the hypothesis that circadian rhythms modulated by clock genes expression as the Periodgenes (PER-1, PER-2, PER-3) are involved in cancer growth, we retrospectively evaluated  PER-2 expression by immunohistochemistry in 59 advanced CRC patients, treated with first line chronomodulated triplet combination (Irinotecan+Oxaliplatin+Folinic Acid+5-Fluorouracil) ± Cetuximab. Immunostaining for PER-2 was correlated to EGFR, ERβ1, ERβ2, Cyclin D1, β-catenin expression and  K-RAS and B-RAF mutational status. We evidenced that PER-2(-) CRC more frequently expressed EGFR (73%) (p>0.0001), ERβ1 (77%) (p=0.07), ERβ2 (88.5%) (p>0.0001), Cyclin D1 (69.2%) (p=0.06). Explorative multiple correspondence analysis showed response to chemotherapy related to a profile including  PER-2 (+), EGFR (-), ERβ1 (-), ERβ2 (-), β-catenin (-) and low expression of miR-206. 2013 proposal: In collaboration with the Department of Oncology/IRE we are planning to evaluate whether different response to anti EGFR therapy may occur in KRAS wild type cases presenting low or high EGFR expression . Furthermore we will evaluate , in a larger series of advanced CRC, if PER-2 loss will  be associated to cell proliferation and response to chemotherapy.
Lung Cancer (NSCLC).Although cytology and tumor biopsy are a very common approaches to evaluate patient eligibility to tyrosine kinase inhibitors (TKIs), the limited number of tumor cells present in these samples may often constitute a bias for EGFR mutational analysis. The aim of this study was twofold: 1) to determine the accuracy and sensitivity in detecting EGFR mutations between liquid-based cytology (LBC) and bioptic specimens, 2) to compare the performance of direct DNA sequencing and real-time PCR (qPCR) in two different series of cytologic and histologic primary and metastatic NSCLC. The overall specimen insufficiency rate between LBC and biopsies was significantly higher by direct sequencing compared to qPCR (biopsies: 11.6% vs 7.2%) and (LBC: 14.7% vs 2.3%). In the series of 309 valuable cases analyzed by direct sequencing (251 bioptic and 58 LBC), we found 34 (11%) EGFR mutations (11.2% biopsies and 10.3% LBC ). Of interest, a higher percentage of EGFR mutant cases (18.1%) was observed in the 170 valuable cases analyzed by qPCR (11.1% biopsies and 21,4% LBC). Our data indicate that TP collected specimens seem to be more reliable than formalin fixed biopsies for molecular analysis, probably due to the better quality of the extracted DNA. Furthermore, qPCR enabled detection of EGFR mutations in samples with low tumor content for which conventional Sanger sequencing was not informative. 2013 proposal: In the context of a network project  among 5 Italian Cancer Centers (Bando RICERCA FINALIZZATA 2011-2012 Ministero della Salute), we will study  1) the potential  application in clinical practice of Next Generation Sequencing (NGS) which allow a wide cancer molecular subtyping detecting known and novel mutations from small quantity of DNA. 2) microRNA expression profiling to determine miRNA landscape in current and former smoker patients. The identification of novel predictive markers will contribute to better select more personalized therapies in NSCLC patients
Ano-Genital HPV Related Diseases. In 2012 we have evaluated the data regarding potential biomarkers in the uterine cervix carcinogenesis. In particular: a. the HPV E6-E7 mRNA assay as a prognostic biomarker (in collaboration with ASP Lazio Sanità, Università “ La Sapienza” di Roma, Università “Gabriele D’Annunzio” di Chieti, Ospedale “F. Renzetti” di Lanciano). b. the diagnostic role of claspin, a proliferation related nuclear protein (in collaboration with Dr A. Musio, ISPO, Florence). c. p16/ki67 dual staining as a biomarker in the cancerogenesis of uterine cervix, correlating the immunoreactivity with the grade of lesions and HPV infection. Moreover,  we have assessed the prevalence and HPV genotype distribution in male populations, i.e. a. Italian clinically healthy eterosexual men and their sexual partners and b. immunocompetent and immunocompromised homosexual men (anal district; in collaboration with MST of ISG). In addition, we conducted a methodological study, comparing the performance of an HPV genotyping test in cytological and histological samples (in collaboration with MST of ISG). 2013 proposals: we are now planning to evaluate: a. the prognostic role of p16/Ki-67 dual staining assay; b. the immunohistochemical expression of hMENA protein, a cytoskeleton regulatory protein involved in adhesion and cell motility, in cervical tissues correlating also with HPV infection (in collaboration with Experimental Oncology dept IRE). c. genital HPV infection in a male population of high grade school students in Rome (in collaboration with “Sapienza” University of Rome and  Società Italiana di Andrologia e Medicina della Sessualità).
Head & Neck Pathology. During 2012 we have carried on the collection of cytological and histological samples from patients with or without lesions of the head & neck district. Samples were morphologically interpreted and analyzed for HPV infection, by different PCR methods, and for p16 expression by immunohisto- immunocytochemistry. Data were recorded in a dedicated database. We have also analyzed head & neck samples from the Karolinska Institute of Stockholm (collaborative study). 2013 proposal: We aim to assess the HPV prevalence, genotype distribution, and p16 role in Head & Neck preneoplastic and neoplastic lesions.  Moreover, we will evaluate cytological sample as a potential tool for screening of oral and oropharingeal lesions. We are also collaborating with dr G. Blandino aiming at correlating HPV status, genotyping and p16 expression with other biomarkers (i.e. p53, miRNAs).
Melanoma.In collaboration with the Immunology Laboratory IRE, we performed immunohistochemical testing using the MEM-E/02 antibody, of more than 100 nevo-melanocytic lesions (conventional sections and tissue arrays), and we found that HLA-E gradually increases with tumor progression: from weak expression in 15% of nevi, to low-intermediate expression in 57% of primaries, to a full range of expression levels (including high homogeneous staining) in 67% of metastatic lesions. 2013 proposal: we have planned to continue the investigation of the expression of HLA molecules in solid tumors, in particular evaluating HLA-E expression using the MEM-E/02 antibody.

Thymic epithelial tumours.The diagnostics of Thymic Epithelial Tumours (TET) has been the focus of our group, contributing in the framework of an international   multicenter study to refinement of diagnostic elements both by conventional morphological criteria and new immunohistochemical markers of cortical/medullary origin. This study is preliminary and in relation with  the revision of the existing pathological TET classification by the World Health Organization. Moreover, our group  as member of an international network dealing with Thymic Epithelial Malignancies (International Thymic Malignancy Interest Group, ITMIG) is contributing to  the International Staging Committee, Thymic domain of the International Association Study Lung Cancer (IASLC) for Thymic Tumor Staging (UICC/AJCC), participating  to the new UICC  Thymic Tumor Staging project. As fundamental  tool contributing to the Thymic Staging project, a world web-based Retrospective Database has been established at  the HubZero Platform of the Purdue University. To this Retrospective database – which collected more than 7000 TET cases around the world- our group is contributing with data and analysis of key indicators in the T, N and M system. New tumor- and subtype specific molecular biologic markers are actually under evaluation in the framework of a collaboration with the Translational Oncogenomic Unit of our Institute, focused on microRNAs produced in TET and available to the study in FFPE tissue.  2013 proposal:  our purposes is to validate our data on EGFR genetic alterations in TET on a second, larger,  patient cohort and to extend  the innovative biomarker (both molecular biological – microRNA- and immunohistochemical – with the HIPK2 antibody provided by Dr S. Soddu from our Institute) evaluation  in TET. Furthermore, a closer collaboration with the major international groups involved in TET diagnosis, staging and research is planned to go on. 

 Pubblicazioni

Nel corso del 2011 e del 2012 sono stati pubblicati i seguenti articoli scientifici (gli autori afferenti alla UOC di Anatomia Patologica sono riportati in grassetto) :

PUBBLICAZIONI  ANNO 2011 (con relativo IMPACT FACTOR sec. JCR, 2010)

1.     Fabi A, Di Benedetto A, Metro G, Perracchio L, Nisticò C, Di Filippo F, Ercolani C, Ferretti G, Melucci E, Buglioni S, Sperduti I, Papaldo P, Cognetti F, Mottolese M. HER2 Protein and Gene Variation between Primary and Metastatic Breast Cancer: Significance and Impact on Patient Care. Clin Cancer Res. 2011 Mar 22. [Epub ahead of print]. (I.F 7.338)
2.     Metro G, Foglietta J, Russillo M, Stocchi L, Vidiri A, Giannarelli D, Crinò L, Papaldo P, Mottolese M, Cognetti F, Fabi A, Gori S. Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Ann Oncol. 2011 Mar;22(3):625-30. Epub 2010 Aug 19. (I.F 6.452 )
3.     Barba M, Sperati F, Stranges S, Carlomagno C, Nasti G, Iaffaioli V, Caolo G, Mottolese M, Botti G, Terrenato I, Vici P, Serpico D, Giordano A, D’Aiuto G, Crispo A, Montella M, Capurso G, Delle Fave G, Fuhrman B, Botti C, De Placido S. Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort. Ann Oncol. 2011 Nov 18 (I.F6.452)
4.     Vici P, Brandi M, Giotta F, Foggi P, Schittulli F, Di Lauro L, Gebbia N, Massidda B, Filippelli G, Giannarelli D, Di Benedetto A, Mottolese M, Colucci G, Lopez M. A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study. Ann Oncol. 2011 Sep 28. (I.F6.452)
5.     Del Giudice I, Messina M, Chiaretti S, Santangelo S, Tavolaro S, De Propris MS, Nanni M, Pescarmona E, Mancini F, Pulsoni A, Martelli M, Di Rocco A, Finolezzi E, Paoloni F, Mauro FR, Cuneo A, Guarini A, Foà R. Behind the scenes of non-nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes. Br J Haematol. 2011 Dec 8. Doi: 10.1111/j.1365-2141.2011.08962.x. (I.F 4.942)
6.     Re A, Aiello A, Nanni S, Grasselli A, Benvenuti V, Pantisano V, Strigari L, Colussi C, Ciccone S, Mazzetti AP, Pierconti F, Pinto F, Bassi P, Gallucci M, Sentinelli S, Trimarchi F, Bacchetti S, Pontecorvi A, Lo Bello M, Farsetti A. Silencing of GSTP1, a Prostate Cancer Prognostic Gene, by the Estrogen Receptor-β and Endothelial Nitric Oxide Synthase Complex. Mol Endocrinol. 2011 Dec;25(12):2003-16. Epub 2011 Nov 3. (I.F.4.889)
7.     Campiglio M, Bufalino R, Sandri M, Ferri E, Aiello RA, De Matteis A, Mottolese M, De Placido S, Querzoli P, Jirillo A, Bottini A, Fantini M, Bonetti A, Pedani F, Mauri M, Molino A, Ferro A, Pupa SM, Sasso M, Ménard S, Balsari A, Tagliabue E. Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study. Breast Cancer Res Treat. 2011 Jul;128(1):147-54. Epub 2011 Apr 11. (I.F 4.859)
8.     Shaaban AM, Ball GR, Brannan RA, Cserni G, Benedetto AD, Dent J, Fulford L, Honarpisheh H, Jordan L, Jones JL, Kanthan R, Maraqa L, Litwiniuk M, Mottolese M, Pollock S, Provenzano E, Quinlan PR, Reall G, Shousha S, Stephens M, Verghese ET, Walker RA, Hanby AM, Speirs V. A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. Breast Cancer Res Treat. 2011 Nov 18. [Epub ahead of print] (I.F4.859)
9.     Benevolo M, Vocaturo A, Caraceni D, French D, Rosini S, Zappacosta R, Terrenato I, Ciccocioppo L, Frega A, Giorgi Rossi P. Sensitivity, specificity and clinical value of HPV E6/E7 mRNA assay as a triage test for cervical cytology and HPV DNA test. J Clin Microbiol. 2011 Jul;49(7):2643-50. Epub 2011 Apr 27.(I.F 4.220)
10. Del Nonno F, Pisani G, Visca P, Signore F, Grillo LR, Baiocchini A, Garbuglia AR, Sepe S, Piacentini M, Falasca L. Role and predictive strength of transglutaminase type 2 expression in premalignant lesions of the cervix. Mod Pathol. 2011 Jun;24(6):855-65. Epub 2011 Mar 25. (I.F. 4.176)
11. Marchevsky A, Marx A, Ströbel P, Suster S, Venuta F, Marino M, Yousem S, Zakowski M. Policies and reporting guidelines for small biopsy specimens of mediastinal masses  J Thorac Oncol. 2011 Jul;6 (7 Suppl 3):S1724-9. (I.F 4.040)
12. Benevolo M, Mottolese M, Tremante E, Rollo F, Diodoro MG, Ercolani C, Sperduti I, Lo Monaco E, Cosimelli M, Giacomini P. High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis. J Transl Med. 2011 Oct 27;9:184. (I.F3.508)
13. Tommasi S, Mangia A, Iannelli G, Chiarappa P, Rossi E, Ottini L, Mottolese M, Zoli W, Zuffardi O, Paradiso A. Gene copy number variation in male breast cancer by aCGH. Cell Oncol (Dordr). 2011 Oct;34(5):467-73. Epub 2011 May 6. Erratum in: Cell Oncol (Dordr). 2011 Oct;34(5):509-10. (I.F 3.175)
14. Donà MG, Benevolo M, Pimpinelli F, Battista M, Rollo F, Stivali F, Moscarelli A, Giuliani M, Di Carlo A, Vocaturo A. Comparative evaluation of different DNA extraction methods for HPV genotyping by linear array and INNO-LiPA. J Med Virol. 2011 Jun;83(6):1042-7. Doi: 10.1002/jmv.22088. (I.F 2.895)
15. Bordignon V, Bultrini S, Prignano G, Sperduti I, Piperno G, Bonifati C, Filippetti M, Toma L, Latini A, Di Cecio M, Giuliani A, Vocaturo A, Trento E, D’ Agosto G, Francesconi F, Cataldo A, Vento A, Cilenti V, Berardesca E, Ameglio F, Cordiali Fei P, Ensoli F. High prevalence of latent tuberculosis infection in autoimmune disorders such as psoriasis and in chronic respiratory diseases, including lung cancer. J Biol Regul Homeost Agents. 2011 Apr-Jun;25(2):213-20 (I.F2.825)
16. Benevolo M, Terrenato I, Mottolese M, Marandino F, Carosi M, Rollo F, Ronchetti L, Muti P, Mariani L, Sindico S, Vocaturo G, Vocaturo A . Diagnostic and prognostic validity of the human papillomavirus E6/E7 mRNA test in cervical cytological samples of HC2-positive patients. Cancer Causes Control. 2011 Jun;22(6):869-75. Doi: 10.1007/s10552-011-9757-0. Epub 2011 Mar 19.(I.F 2.789)
17. Palmieri G, Marino M, · Buonerba C ,· Federico P, · Conti ·S, Milella M, · Petillo L ,· Evoli A ,· Lalle M ,· Ceribelli A, · Merola G · Matano E, · Sioletic S, · De Placido S, · Di Lorenzo G ,· Damiano V. Cancer Chemother Pharmacol. 2012 Feb;69(2):309-15. Epub 2011 Jun 28 (I.F. 2.759)
18. Ferrari A, Zalaudek I, Argenziano G, Buccini P, De Simone P, Silipo V, Eibenschutz L, Mariani G, Covello R, Sperduti I, Mariani L, Catricalà C. Dermoscopy of Pigmented Lesions of the Vulva: A Retrospective Morphological Study. Dermatology. 2011;222(2):157-66. Epub 2011 Feb 9. (I.F. 2.714)  
19. Licci S, Morelli L, Covello R. Primary mantle cell lymphoma of the testis. Ann Hematol. 2011 Apr;90(4):483-4. Epub 2010 Aug 17. 8 (I.F.2.688)
20. Paolini F, Rollo F, Brandi R, Benevolo M, Mariani L, Cercato MC, Vocaturo A, Venuti A. High risk human papillomavirus genotyping in clinical samples: evaluation of different commercial tests. Int J Immunopathol Pharmacol. 2011 Jan-Mar;24(1):127-38. (I.F 2.685) 
21. Ganci F, Conti S, Fontemaggi G, Manciocco V, Donzelli S, Covello R, Muti P, Strano S, Blandino G, Spriano  G. Allelic Expression Imbalance of TP53 Mutated and Polymorphic Alleles in Head and Neck Tumors. OMICS. 2011 Feb 24. (I.F. 1.944)
22. Paolini F, Carbone A, Benevolo M, Silipo V, Rollo F, Covello R, Piemonte P, Frascione P, Capizzi R, Catricala C, Venuti A. Human Papillomaviruses, 16INK4a and Akt expression in basal cell carcinoma. J Exp Clin Cancer Res. 2011 Nov 14;30(1):108. [Epub ahead of print] (I.F 1.921)
23. Carboni F; Valle M; Garofano A; Carosi M. Laparoscopic Excision of a Sintomatic Brunneroma. American Surgeon  pp. E37-E38(2) Volume 77; Number 2; February 2011 (I.F. 1.363) 
24. Covello R, Licci S, Pichi B, Spriano G, Vidiri A, Morelli L, Rosenberg AE. Low-Grade Myofibroblastic Sarcoma of the Larynx.. Int J Surg Pathol. 2011 Jan 12. [Epub ahead of print]. (I.F. 1.134)
25. Mercante G, Marchesi A, Covello R, Dainese L, Spriano G. Mixed squamous cell carcinoma and follicular carcinoma of the thyroid gland. Auris Nasus Larynx. 2011 Aug 18. [Epub ahead of print]  (I.F 0.711)
26. Pichi B, Terenzi V, Covello R, Spriano G. Cricoid-based extramedullary plasmocytoma. J Craniofac Surg. 2011 Nov;22(6):2361-3. (I.F 0.772)
27. Russillo M, Di Benedetto A, Metro G, Ferretti G, Papaldo P, Cognetti F, Mottolese M, Fabi A. Assessment of PTEN and PI3K Status in Primary Breast Cancer and Corresponding Metastases: Is It Worthwhile?. J Clin Oncol. 2011 Jun 13. [Epub ahead of print] Letter. No abstract available. (I.F 18.970)
Pubblicazioni non recensite su PUBMED/MEDLINE
1.     Zoccali C, Chichierchia G, Covello R; An unusual case of lumbar paravertebral miositis ossificans mimicking muscular skeletal tumor. Musculoskelet Surg. 2011 Nov 12
2.     Pelagio G, Pistillo D, and Mottolese M. Minimum Biobanking Requirements:Issues in a Comprehensive Cancer Center Biobank.Biopreservation and Biobanking Volume 9, Number 2, 2011
3.     Marino M, Piantelli M. Immunohistochemistry of thymic epithelial tumors as a tool in translational research. Thorac Surg Clin. 2011 Feb;21(1):33-46, vi. Review
 
PUBBLICAZIONI  ANNO 2012 (con relativo IMPACT FACTOR sec. JCR, 2011) 
  1. Tremante E, Ginebri A, Lo Monaco E, Frascione P, Di Filippo F, Terrenato I, Benevolo M, Mottolese M, Pescarmona E, Visca P, Natali PG, Giacomini P. Melanoma molecular classes and prognosis in the postgenomic era. Lancet Oncol. 2012 May;13(5):e205-11. (I.F. 22.589)
  2. Biagioni F, Bossel Ben-Moshe N, Fontemaggi G, Canu V, Mori F, Antoniani B, Di Benedetto A, Santoro R, Germoni S, De Angelis F, Cambria A, Avraham R, Grasso G, Strano S, Muti P, Mottolese M, Yarden Y, Domany E, Blandino G. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours. EMBO Mol Med. 2012 Nov;4(11):1214-29. doi: 10.1002/emmm.201201483. (IF 10.333)
  3. Di Modugno F, Iapicca P, Boudreau A, Mottolese M, Terrenato I, Perracchio L, Carstens RP, Santoni A, Bissell MJ, Nisticò P. Splicing program of human MENA produces a previously undescribed isoform associated with invasive, mesenchymal-like breast tumors. Proc Natl Acad Sci U S A. 2012 Nov 5. [Epub ahead of print].  (I.F.9.681)
  4. Schito L, Rey S, Tafani M, Zhang H, Wong CC, Russo A, Russo MA, Semenza GL. Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells. P Natl Acad Sci U S A. 2012 Sep 10. ( IF. 9.681)
  5. Vici P, Brandi M, Giotta F, Foggi P, Schittulli F, Di Lauro L, Gebbia N, Massidda B, Filippelli G, Giannarelli D, Di Benedetto A, Mottolese M, Colucci G, Lopez M. A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study.Ann Oncol. 2012 May;23(5):1121-9. (IF 6.425)
  6. Barba M, Sperati F, Stranges S, Carlomagno C, Nasti G, Iaffaioli V, Caolo G, Mottolese M, Botti G, Terrenato I, Vici P, Serpico D, Giordano A, D'Aiuto G, Crispo A, Montella M, Capurso G, Delle Fave G, Fuhrman B, Botti C, De Placido S. Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort. Ann Oncol. 2012 Jul;23(7):1838-45. (I.F. 6.425)
  7. Paris O, Ferraro L, Grober OM, Ravo M, De Filippo MR, Giurato G, Nassa G, Tarallo R, Cantarella C, Rizzo F, Di Benedetto A, Mottolese M, Benes V, Ambrosino C, Nola E, Weisz A. Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer. Oncogene. 2012 Jan 9. (I.F. 6.373) 
  8. Lattanzio R, Marchisio M, La Sorda R, Tinari N, Falasca M, Alberti S, Miscia S, Ercolani C, Di Benedetto A, Perracchio L, Melucci E, Iacobelli S, Mottolese M, Natali PG, Piantelli M; on behalf of CINBO (Consorzio Interuniversitario Nazionale per la Bio-Oncologia). Overexpression of activated phospholipase Cγ1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy. Int J Cancer. 2012 Jul 31. doi: 10.1002/ijc.27751. (IF. 5.444)
  9. Folgiero V, Di Carlo  SE,  Bon G, Spugnini EP, Di Benedetto A, Germoni S, Gentileschi, M P, Accardo A, Milella, Morelli M G, Bossi G, Mottolese M and Falcioni R , Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast cancer cells. Cell Death and Disease (2012) 3, e440; doi:10.1038/cddis.2012.179 (I.F 5.333)
  10. Sacconi A, Biagioni F, Canu V, Mori F, Di Benedetto A, Lorenzon L, Ercolani C, Di Agostino S, Cambria AM, Germoni S, Grasso G, Blandino R, Panebianco V, Ziparo V, Federici O, Muti P, Strano S, Carboni F, Mottolese M, Diodoro M, Pescarmona E, Garofalo A, Blandino G. miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis. 2012 Nov 15;3:e423. doi: 10.1038/cddis.2012.160. (I.F 5.333)
  11. Del GiudiceI, Messina M, Chiaretti S, Santangelo S, Tavolaro S, De Propris MS, Nanni M, PescarmonaE, Mancini F, Pulsoni A, Martelli M, Di Rocco A, Finolezzi E, Paoloni F, Mauro FR, Cuneo A, Guarini A, Foà R. Behind the scenes of non-nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes. Br J Haematol. 2012 Mar;156(5): (I.F 4.941)
  12. Shaaban AM, Ball GR, Brannan RA, Cserni G, Benedetto AD, Dent J, Fulford L, Honarpisheh H, Jordan L, Jones JL, Kanthan R, Maraqa L, Litwiniuk M, Mottolese M, Pollock S, Provenzano E, Quinlan PR, Reall G, Shousha S, Stephens M, Verghese ET, Walker RA, Hanby AM, Speirs V. A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. Breast Cancer Res Treat. 2012 Jun;133(3):949-58.(I.F. 4.431)
  13. Salvatori L, Caporuscio F, Verdina A, Starace G, Crispi S, Nicotra MR, Russo A, Calogero RA, Morgante E, Natali PG, Russo MA, Petrangeli E.  Cell-to-Cell Signaling Influences the Fate of Prostate Cancer Stem Cells and Their Potential to Generate More Aggressive Tumors. PLoS One. 2012;7(2):e31467. (I.F. 4.092)
  14. Donà MG, Palamara G, Di Carlo A, Latini A, Vocaturo A, Benevolo M, Pimpinelli F, Giglio A, Moretto D, Impara G, Giuliani M. Prevalence, genotype diversity and determinants of anal HPV infection in HIV-uninfected men having sex with men.J Clin Virol. 2012 Jun;54(2):185-9. (I.F 3.969)
  15. Donà MG, Vocaturo A, Giuliani M, Ronchetti L, Rollo F, Pescarmona E, Carosi M, Vocaturo G, Benevolo M. p16/Ki-67 dual staining in cervico-vaginal cytology: Correlation with histology, Human Papillomavirus detection and genotyping in women undergoing colposcopy. Gynecol Oncol. 2012 May 12. (I.F 3.888)
  16. Milella M, Nuzzo C, Bria E, Sperduti I, Visca P, Buttitta F, Antoniani B, Merola R, Gelibter A, Cuppone F, D'Alicandro V, Ceribelli A, Rinaldi M, Cianciulli A, Felicioni L, Malatesta S, Marchetti A, Mottolese M, Cognetti F. EGFR molecular profiling in advanced NSCLC: a prospective phase II study in molecularly/clinically selected patients pretreated with chemotherapy.J Thorac Oncol. 2012 Apr;7(4):672-80.(IF 3.661)
  17. Benevolo M, Musio A, Vocaturo A, Donà MG, Rollo F, Terrenato I, Carosi M, Pescarmona E, Vocaturo G, Mottolese M. Claspin as a biomarker of Human Papillomavirus-related High Grade lesions of uterine cervix.  J Transl Med. 2012 Jun 25;10(1):132. (I.F.3.474).
  18. Calatozzolo C, Pollo B, Botturi A, Dinapoli L, Carosi M, Salmaggi A, Maschio M. Multidrug resistance proteins expression in glioma patients with epilepsy. J Neuro oncol. 2012 Oct;110(1):129-35. Epub 2012 Jul 26. (IF.3.214). 
  19. Rossi L, Veltri E, Zullo A, Zoratto F, Colonna M, Di Seri M, Longo F, Mottolese M, Giannarelli D, Ruco L, Romiti A, Barucca V, Adua D, Tomao S. Bevacizumab plus chemotherapy in metastatic colorectal cancer patients treated in clinical practice.Future Oncol. 2012 Sep;8(9):1193-7. doi: 10.2217/fon.12.108.  (I.F. 3.163)
  20. Donà MG, Benevolo M, Vocaturo A, Palamara G, Latini A, Giglio A, Moretto D, Rollo F, Impara G, Ensoli F, Pimpinelli F, Di Carlo A, Giuliani M. Anal cytological abnormalities and epidemiological correlates among men who have sex with men at risk for HIV-1 infection. BMC Cancer. 2012 Oct 16;12(1):476. doi: 10.1186/1471-2407-12-476. (I.F. 3.011)
  21. Santoro A, Pannone G, Carosi MA, Francesconi A, Pescarmona E, Russo GM, Feola A, Losito S, Franco R, Nappi L, Aquino G, De Rosa G, Di Domenico M, Bufo P. BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy. J Cell Biochem. 2012 Nov 28. doi: 10.1002/jcb.24460. [Epub ahead of print]  (I.F. 2.868)
  22. Zoccali C, Covello R, Di Francesco A, Zoccali G. Eur J Surg Oncol. A cyanoacrylate and silastic patch to reduce the risk of opening of the tumor: Technical note. Eur J Surg Oncol. 2012 Sep 30. pii: S0748-7983(12)01234-6. doi: 10.1016/j.ejso.2012.08.025. [Epub ahead of print] (I.F.  2.499)
  23. Fruci D, Benevolo M, Cifaldi L, Lorenzi S, Lo Monaco E, Tremante E, Giacomini P. Major histocompatibility complex class i and tumour immuno-evasion: how to fool T cells and natural killer cells at one time. Curr Oncol. 2012 Feb;19(1):39-41. (I.F 2.473)
  24. Abbruzzese C, Mattarocci S, Pizzuti L, Mileo AM, Visca P, Antoniani B, Alessandrini G, Facciolo F, Amato R, D'Antona L, Rinaldi M, Felsani A, Perrotti N, Paggi MG. Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas.J Exp Clin Cancer Res. 2012 Jan 12;31:4. (I.F 2.148)
  25. Cristalli G, Mercante G, Covello R, Sperduti I, Cristalli MP, Spriano G. Histopathological Assessment in Glossectomy: Harmonic Shears versus Monopolar Electrosurgery Pilot Study. Otolaryngol Head Neck Surg. 2012 Aug 7. (IF 1.718)
  26. Lorenzon L, Benevolo M, Visca P, Venturo I, Filippetti M, Piro FR, Rollo F, Vocaturo A. Human Papillomavirus Type 16 DNA Detected in Pulmonary Metastases From a Penile Squamous Cell Carcinoma: A Case Study. Int J Surg Pathol. 2012 Jun 6. (I.F. 1.000)
  27. Mercante G, Marchesi A, Covello R, Dainese L, Spriano G. Mixed squamous cell carcinoma and follicular carcinoma of the thyroid gland. Auris Nasus Larynx. 2012 Jun;39(3):310-3. (I.F. 0.761)
Pubblicazioni non recensite su PUBMED/MEDLINE

1.      Palmieri G, Buonerba C, Federico P, Formisano L, Nappi L, Lorenzo GD, Marino M, Damiano V. Everolimus plus long-acting somatostatin analogs in thymic epithelial malignancies. World J Clin Oncol. 2012 Jul 10;3(7):111-5.

Giorgi Rossi P, Sideri M, Carozzi FM, Vocaturo A, Buonaguro FM, Tornesello ML, Burroni E, Mariani L, Boveri S, Zaffina LM, Chini F; the HPV Prevalence Italian Working Group. HPV type distribution in invasive cervical cancers in Italy: pooled analysis of three large studies. Infect Agent Cancer. 2012 Oct 12;7(1):26. (I.F. 3.17) Impact Factor non ufficiale