Anna Sapino
e-mail: anna.sapino AT unito.it
affiliation: Università di Torino
research area(s): Cancer Biology, Experimental Medicine
Course:
Biomedical Sciences and Human Oncology
University/Istitution: Università di Torino
University/Istitution: Università di Torino
Education and training
1982: University of Turin
1986: Professional specialist, Faculty of Medicine, University of Milan
1987: Sabbatical USA
1982: Graduated at Medical School, Magna cum laude
1986: Degree as a MD specialized in Pathological Anatomy and Histology, University of Milan
1987: Fellowship sponsored by the Lega Italiana per la Lotta contro i Tumori on Study of pre-neoplastic breast lesions: experimental and practical approach
Subjects: Pathological Anatomy and Histology. Breast cancer.
Occupational skills: Brightfield microscopy. Fluorescence microscopy. Cell cultures. Molecular biology.
University professor, Associate Medical Director (University of Turin, Dept. of Biomedical Sciences & Human Oncology, Ospedale "Molinette" Torino)
University and post-University teaching activity. Full Professor of Pathological Anatomy and Histology.
Scientific Research in the field of Experimental and Clinico-Pathological studies on breast cancer.
Management and responsibility of the Pathological Anatomy and Histology Unit and Breast Unit San Giovanni Hospital Turin, of the Center for the Screening of Cervix Vaginal Cancer of City of Turin, Responsible for Quality Assurance for prognostic and predictive factors in breast cancer of the Regional Oncology Web.
Principal Investigator and coordinator of multidisciplinary research projects, both national. Collaboration to numerous international project as external consultant. Member of the European Group of Breast Pathology Screening.
1982: University of Turin
1986: Professional specialist, Faculty of Medicine, University of Milan
1987: Sabbatical USA
1982: Graduated at Medical School, Magna cum laude
1986: Degree as a MD specialized in Pathological Anatomy and Histology, University of Milan
1987: Fellowship sponsored by the Lega Italiana per la Lotta contro i Tumori on Study of pre-neoplastic breast lesions: experimental and practical approach
Subjects: Pathological Anatomy and Histology. Breast cancer.
Occupational skills: Brightfield microscopy. Fluorescence microscopy. Cell cultures. Molecular biology.
University professor, Associate Medical Director (University of Turin, Dept. of Biomedical Sciences & Human Oncology, Ospedale "Molinette" Torino)
University and post-University teaching activity. Full Professor of Pathological Anatomy and Histology.
Scientific Research in the field of Experimental and Clinico-Pathological studies on breast cancer.
Management and responsibility of the Pathological Anatomy and Histology Unit and Breast Unit San Giovanni Hospital Turin, of the Center for the Screening of Cervix Vaginal Cancer of City of Turin, Responsible for Quality Assurance for prognostic and predictive factors in breast cancer of the Regional Oncology Web.
Principal Investigator and coordinator of multidisciplinary research projects, both national. Collaboration to numerous international project as external consultant. Member of the European Group of Breast Pathology Screening.
The scientific activity is focused on Experimental and Clinico-Pathological studies on breast cancer, The key mission is to translate the achievements of basic science to the patient's bedside. In the last years she has focused on prognostic and predictive factors in breast cancer. For these studies she has obtained grants from the Ministry of Health and of the University, from the Associazione Italiana Ricerca sul Cancro (AIRC), from Piedmont Region and from the Istituto San Paolo and Cassa di Risparmio. She leads a well consolidated research group and can count on the collaboration of basic and clinical scientists with different cultural backgrounds, including biochemical and biological sciences, biotechnologies and oncology.
The results of these studies have been presented to National and International Meetings and published on peer-reviewed international journals. Prof. Sapino has lectured extensively at national and international meetings. She is Referee for international scientific journals.
AWARDS
International Academy of Pathology award "Cesare Biancifiori" for the scientific work: "Estrogen and tamoxifen induced rearrangement of cytoskeletal and adhesion structures in breast cancer MCF-7 cells" (Cancer Research 46:2526-2531, 1986).
The results of these studies have been presented to National and International Meetings and published on peer-reviewed international journals. Prof. Sapino has lectured extensively at national and international meetings. She is Referee for international scientific journals.
AWARDS
International Academy of Pathology award "Cesare Biancifiori" for the scientific work: "Estrogen and tamoxifen induced rearrangement of cytoskeletal and adhesion structures in breast cancer MCF-7 cells" (Cancer Research 46:2526-2531, 1986).
Castellano I, Allia E, Accortanzo V, Vandone AM, Chiusa L, Arisio R, Durando A, Donadio M, Bussolati G, Coates AS, Viale G, Sapino A. Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers. Breast Cancer Res Treat. 2010 Dec;124(3):607-17. Epub 2010 Feb 3.
Castellano I, Marchiò C, Tomatis M, Ponti A, Casella D, Bianchi S, Vezzosi V, Arisio R, Pietribiasi F, Frigerio A, Mano MP, Ricardi U, Allia E, Accortanzo V, Durando A, Bussolati G, Tot T, Sapino A. Micropapillary ductal carcinoma in situ of the breast: an inter-institutional study. Mod Pathol. 2010 Feb;23(2):260-9. Epub 2009 Nov 13.
Marchiò C, Lambros MB, Gugliotta P, Di Cantogno LV, Botta C, Pasini B, Tan DS, Mackay A, Fenwick K, Tamber N, Bussolati G, Ashworth A, Reis-Filho JS, Sapino A. Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. J Pathol. 2009 Sep;219(1):16-24.
Senetta R, Campanino PP, Mariscotti G, Garberoglio S, Daniele L, Pennecchi F, Macrì L, Bosco M, Gandini G, Sapino A. Columnar cell lesions associated with breast calcifications on vacuum-assisted core biopsies: clinical, radiographic, and histological correlations. Mod Pathol. 2009 Jun;22(6):762-9. Epub 2009 Mar 13.
Daniele L, Sapino A. Anti-HER2 treatment and breast cancer: state of the art,
Prunotto M, Bosco M, Daniele L, Macri' L, Bonello L, Schirosi L, Rossi G, Filosso P, Mussa B, Sapino A. Imatinib inhibits in vitro proliferation of cells derived from a pleural solitary fibrous tumor expressing platelet-derived growth factor receptor-beta. Lung Cancer. 2009 May;64(2):244-6. Epub 2008 Nov 28.
Daniele L, Annaratone L, Allia E, Mariani S, Armando E, Bosco M, Macrì L, Cassoni P, D'Armento G, Bussolati G, Cserni G, Sapino A. Technical limits of comparison of step-sectioning,immunohistochemistry and RT-PCR on breast cancer sentinel nodes: a study on methacarn-fixed tissue. J Cell Mol Med. 2009 Sep;13(9B):4042-50. Epub 2008 Jul 30.
Bussolati G, Marchiò C, Gaetano L, Lupo R, Sapino A. Pleomorphism of the nuclear envelope in breast cancer: a new approach to an old problem. J Cell Mol Med. 2008 Jan-Feb;12(1):209-18. Epub 2007 Dec 5.
Sapino A, Montemurro F, Marchiò C, Viale G, Kulka J, Donadio M, Bottini A, Botti G, dei Tos AP, Bersiga A, Di Palma S, Truini M, Sanna G, Aglietta M, Bussolati G. Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study. Ann Oncol. 2007 Dec;18(12):1963-8. Epub 2007 Sep 4.
Daniele L, Macrì L, Schena M, Dongiovanni D, Bonello L, Armando E, Ciuffreda L, Bertetto O, Bussolati G, Sapino A. Predicting gefitinib responsiveness in lung cancer by fluorescence in situ hybridization/chromogenic in situ hybridization analysis of EGFR and HER2 in biopsy and cytology specimens. Mol Cancer Ther. 2007 Apr;6(4):1223-9. Epub 2007 Apr 3.
Sapino A, Marchiò C, Senetta R, Castellano I, Macrì L, Cassoni P, Ghisolfi G, Cerrato M, D'Ambrosio E, Bussolati G. Routine assessment of prognostic factors in breast cancer using a multicore tissue microarray procedure. Virchows Arch. 2006 Sep;449(3):288-96. Epub 2006 Jun 13.
Marchiò C, Iravani M, Natrajan R, Lambros MB, Geyer FC, Savage K, Parry S, Tamber N, Fenwick K, Mackay A, Schmitt FC, Bussolati G, Ellis I, Ashworth A, Sapino A, Reis-Filho JS. Mixed micropapillary-ductal carcinomas of the breast: a genomic and immunohistochemical analysis of morphologically distinct components. J Pathol. 2009 Jul;218(3):301-15.
Marchiò C, Natrajan R, Shiu KK, Lambros MB, Rodriguez-Pinilla SM, Tan DS, Lord CJ, Hungermann D, Fenwick K, Tamber N, Mackay A, Palacios J, Sapino A, Buerger H, Ashworth A, Reis-Filho JS. The genomic profile of HER2-amplified breast cancers: the influence of ER status. J Pathol. 2008 Dec;216(4):399-407.
Marchiò C, Iravani M, Natrajan R, Lambros MB, Savage K, Tamber N, Fenwick K, Mackay A, Senetta R, Di Palma S, Schmitt FC, Bussolati G, Ellis LO, Ashworth A, Sapino A, Reis-Filho JS. Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast. J Pathol. 2008 Aug;215(4):398-410.
Cserni G, Amendoeira I, Bianchi S, Chmielik E, Degaetano J, Faverly D, Figueiredo P, Foschini MP, Grabau D, Jacquemier J, Kaya H, Kulka J, Lacerda M, Liepniece-Karele I, Penuela JM, Quinn C, Regitnig P, Reiner-Concin A, Sapino A, van Diest PJ, Varga Z, Vezzosi V, Wesseling J, Zolota V, Zozaya E, Wells CA. Distinction of isolated tumour cells and micrometastasis in lymph nodes of breast cancer patients according to the new Tumour Node Metastasis (TNM) definitions. Eur J Cancer. 2011 Apr;47(6):887-94. Epub 2010 Dec 16.
Castellano I, Marchiò C, Tomatis M, Ponti A, Casella D, Bianchi S, Vezzosi V, Arisio R, Pietribiasi F, Frigerio A, Mano MP, Ricardi U, Allia E, Accortanzo V, Durando A, Bussolati G, Tot T, Sapino A. Micropapillary ductal carcinoma in situ of the breast: an inter-institutional study. Mod Pathol. 2010 Feb;23(2):260-9. Epub 2009 Nov 13.
Marchiò C, Lambros MB, Gugliotta P, Di Cantogno LV, Botta C, Pasini B, Tan DS, Mackay A, Fenwick K, Tamber N, Bussolati G, Ashworth A, Reis-Filho JS, Sapino A. Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. J Pathol. 2009 Sep;219(1):16-24.
Senetta R, Campanino PP, Mariscotti G, Garberoglio S, Daniele L, Pennecchi F, Macrì L, Bosco M, Gandini G, Sapino A. Columnar cell lesions associated with breast calcifications on vacuum-assisted core biopsies: clinical, radiographic, and histological correlations. Mod Pathol. 2009 Jun;22(6):762-9. Epub 2009 Mar 13.
Daniele L, Sapino A. Anti-HER2 treatment and breast cancer: state of the art,
Prunotto M, Bosco M, Daniele L, Macri' L, Bonello L, Schirosi L, Rossi G, Filosso P, Mussa B, Sapino A. Imatinib inhibits in vitro proliferation of cells derived from a pleural solitary fibrous tumor expressing platelet-derived growth factor receptor-beta. Lung Cancer. 2009 May;64(2):244-6. Epub 2008 Nov 28.
Daniele L, Annaratone L, Allia E, Mariani S, Armando E, Bosco M, Macrì L, Cassoni P, D'Armento G, Bussolati G, Cserni G, Sapino A. Technical limits of comparison of step-sectioning,immunohistochemistry and RT-PCR on breast cancer sentinel nodes: a study on methacarn-fixed tissue. J Cell Mol Med. 2009 Sep;13(9B):4042-50. Epub 2008 Jul 30.
Bussolati G, Marchiò C, Gaetano L, Lupo R, Sapino A. Pleomorphism of the nuclear envelope in breast cancer: a new approach to an old problem. J Cell Mol Med. 2008 Jan-Feb;12(1):209-18. Epub 2007 Dec 5.
Sapino A, Montemurro F, Marchiò C, Viale G, Kulka J, Donadio M, Bottini A, Botti G, dei Tos AP, Bersiga A, Di Palma S, Truini M, Sanna G, Aglietta M, Bussolati G. Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study. Ann Oncol. 2007 Dec;18(12):1963-8. Epub 2007 Sep 4.
Daniele L, Macrì L, Schena M, Dongiovanni D, Bonello L, Armando E, Ciuffreda L, Bertetto O, Bussolati G, Sapino A. Predicting gefitinib responsiveness in lung cancer by fluorescence in situ hybridization/chromogenic in situ hybridization analysis of EGFR and HER2 in biopsy and cytology specimens. Mol Cancer Ther. 2007 Apr;6(4):1223-9. Epub 2007 Apr 3.
Sapino A, Marchiò C, Senetta R, Castellano I, Macrì L, Cassoni P, Ghisolfi G, Cerrato M, D'Ambrosio E, Bussolati G. Routine assessment of prognostic factors in breast cancer using a multicore tissue microarray procedure. Virchows Arch. 2006 Sep;449(3):288-96. Epub 2006 Jun 13.
Marchiò C, Iravani M, Natrajan R, Lambros MB, Geyer FC, Savage K, Parry S, Tamber N, Fenwick K, Mackay A, Schmitt FC, Bussolati G, Ellis I, Ashworth A, Sapino A, Reis-Filho JS. Mixed micropapillary-ductal carcinomas of the breast: a genomic and immunohistochemical analysis of morphologically distinct components. J Pathol. 2009 Jul;218(3):301-15.
Marchiò C, Natrajan R, Shiu KK, Lambros MB, Rodriguez-Pinilla SM, Tan DS, Lord CJ, Hungermann D, Fenwick K, Tamber N, Mackay A, Palacios J, Sapino A, Buerger H, Ashworth A, Reis-Filho JS. The genomic profile of HER2-amplified breast cancers: the influence of ER status. J Pathol. 2008 Dec;216(4):399-407.
Marchiò C, Iravani M, Natrajan R, Lambros MB, Savage K, Tamber N, Fenwick K, Mackay A, Senetta R, Di Palma S, Schmitt FC, Bussolati G, Ellis LO, Ashworth A, Sapino A, Reis-Filho JS. Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast. J Pathol. 2008 Aug;215(4):398-410.
Cserni G, Amendoeira I, Bianchi S, Chmielik E, Degaetano J, Faverly D, Figueiredo P, Foschini MP, Grabau D, Jacquemier J, Kaya H, Kulka J, Lacerda M, Liepniece-Karele I, Penuela JM, Quinn C, Regitnig P, Reiner-Concin A, Sapino A, van Diest PJ, Varga Z, Vezzosi V, Wesseling J, Zolota V, Zozaya E, Wells CA. Distinction of isolated tumour cells and micrometastasis in lymph nodes of breast cancer patients according to the new Tumour Node Metastasis (TNM) definitions. Eur J Cancer. 2011 Apr;47(6):887-94. Epub 2010 Dec 16.
Project Title:
Tumour microenvironment and cell polarity in breast cancer: roles and implications for metastasis
Background: We have demonstrated that Invasive Micropapillary Carcinomas (IMPCs) harbour genetic aberrations consistent with those of the luminal B subgroup of ER positive breast cancers. IMPCs are prone to early lymphovascular invasion and lymph node metastases. IMPC morphology is reproduced in inflammatory breast carcinomas characterized by florid invasion of lymphatic vessels. The type of stromal and vascular invasion observed in IMPCs may be assimilated to the �Collective Cell Migration� (CCM) phenomenon, which shares similarities, but also important differences, to individually migrating cells. Three mechanisms may be involved in a CCM-like event in IMPCs: i) the tightness of the micropapillae, warranted by the expression of E- and Ncadherin; ii) the inverted polarity of the micropapillae expressing MUC1, a membrane-bound glycoprotein, at the basal rather than at the luminal surface of the cells; iii) the peculiar spongy appearance of the stroma, lined by slender fibroblasts, that may generate tracks wide enough to accommodate the micropapillae. Indeed, in many cases stromal-associated-fibroblasts are capable of producing a wide range of growth factors, cytokines and metalloproteinases (MMPs) that promote extra-cellular matrix degradation and generate paths of least mechanical resistance. We have already proved that treatment of MCF7 ER-positive breast cancer cells with neutrophil elastase, a serine protease, produces inverted-3D-spheroids expressing MUC1 at the outer border of the cell clusters.
Aims: 1. to explore the relationship between hormone receptor status and clustering and inversion of epithelial cancer cells; 2. to evaluate the relationship between stromal cells and invasiveness as inverted tumour clusters; 3. to validate new markers of prognosis and response to treatment in luminal B breast cancers.
Materials and Methods Each objective will be studied as follows: 1. We will perform in vitro studies to evaluate: i) the elastase activity on ER-positive and ERnegative breast cancer cells; ii) the relationship between hormone treatment and inverted- 3D-spheroids formation; iii) the effect of inverted-3D-spheroids on tamoxifen and fulvestrant treatment; iv) the integrins and tight-junction proteins of inverted 3D-spheroids as possible activators of MT1-MMP, a collagenase highly involved in tumor invasion. 2. We will produce: i) short-term cultures of stromal and epithelial cells from IMPCs and non- IMPC breast cancers. The amount of MMPs and elastase will be studied in the supernatant of stromal cells; ii) co-culture model of IMPC and non-IMPC fibroblasts and 3D-spheroids to study paracrine effects of cancer-associated stromal cells on the growth of breast carcinoma cells, and on formation of inverted 3D-spheroids. 3. Genome analysis (Prof. E. Medico) of epithelial and stromal cells in IMPCs as compared to non-IMPC. Interesting differentially expressed genes will be validated by Real-Time PCR technique on a large cohort of samples. If antibodies will be commercially available, immunohistochemistry will be optimized and protein expression will be validated using this technique on tissue sections.
Potential clinical relevance Knowledge of the molecular mechanisms of inverted micropapillary growth and of its susceptibility to lymphovascular emboli formation might lead to improve the management of ER-positive breast cancer.
Aims: 1. to explore the relationship between hormone receptor status and clustering and inversion of epithelial cancer cells; 2. to evaluate the relationship between stromal cells and invasiveness as inverted tumour clusters; 3. to validate new markers of prognosis and response to treatment in luminal B breast cancers.
Materials and Methods Each objective will be studied as follows: 1. We will perform in vitro studies to evaluate: i) the elastase activity on ER-positive and ERnegative breast cancer cells; ii) the relationship between hormone treatment and inverted- 3D-spheroids formation; iii) the effect of inverted-3D-spheroids on tamoxifen and fulvestrant treatment; iv) the integrins and tight-junction proteins of inverted 3D-spheroids as possible activators of MT1-MMP, a collagenase highly involved in tumor invasion. 2. We will produce: i) short-term cultures of stromal and epithelial cells from IMPCs and non- IMPC breast cancers. The amount of MMPs and elastase will be studied in the supernatant of stromal cells; ii) co-culture model of IMPC and non-IMPC fibroblasts and 3D-spheroids to study paracrine effects of cancer-associated stromal cells on the growth of breast carcinoma cells, and on formation of inverted 3D-spheroids. 3. Genome analysis (Prof. E. Medico) of epithelial and stromal cells in IMPCs as compared to non-IMPC. Interesting differentially expressed genes will be validated by Real-Time PCR technique on a large cohort of samples. If antibodies will be commercially available, immunohistochemistry will be optimized and protein expression will be validated using this technique on tissue sections.
Potential clinical relevance Knowledge of the molecular mechanisms of inverted micropapillary growth and of its susceptibility to lymphovascular emboli formation might lead to improve the management of ER-positive breast cancer.