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Faculty Detail    
Name MARGARET S BRANDWEIN-GENSLER
 
Campus Address NP 3545 Zip 6823
Phone 205-934-1602
E-mail mgensler@uab.edu
Other websites http://www.cambridge.org/uk/catalogue/catalogue.asp?isbn=9780521879996
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Anatomic Pathology Professor
Center  Center for AIDS Research  Center for AIDS Research Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations
Molecular and Cellular Pathology Program 

Biographical Sketch 
Dr Brandwein-Gensler was born in New York, where she attended college. She received her medical degree from Upstate Medical College in Syracuse, NY. She was a pathology resident at Mount Sinai Medical Center, NY, and completed a fellowship in Surgical Pathology at Memorial Sloan Kettering Cancer Center. She was member of the pathology faculty at Mount Sinai Medical Center (1990 - 2004), and then Professor of Pathology and Otolaryngology, and Section Head of Head and Neck Pathology at Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY (2004 - 2009). She is past president of the North American Society for Head and Neck Pathology. Her textbook, "Head and Neck" has been published as part of the Cambridge Press Illustrated Surgical Pathology series. Dr Brandwein-Gensler heads the Surgical Pathology Section at the Division of Anatomic Pathology, Department of Pathology.

Society Memberships
Organization Name Position Held Org Link
American Academy of Otolaryngology, Head and Neck Surgery  Associate Member   
Association of Directors of Anatomic and Surgical Pathology      
North American Society for Head and Neck Pathology  past president  http://www.headandneckpathology.com/ 
U.S. and Canadian Academy of Pathology (International Academy of Pathology)   Fellow   

Research/Clinical Interest
Title
Prognostication of Head and Neck Cancer
Description
I have developed and validated a predictive model for patients with head and neck squamous cell carcinoma (SCC) referred to as the Risk Model. A Phase 2 multicenter validation study of nearly 300 patients with low-stage oral SCC has been recently completed published. The Risk Model is presently the only validated model for patients with low-stage oral SCC that predicts treatment failure. This model can potentially shift treatment paradigms as low-stage/high-risk patients could be offered adjuvant radiotherapy based on the weight of published evidence. on study of Stage I/II patients with oral/oropharyngeal squamous carcinoma. I am also focusing on the immune response to carcinoma, one of the features of my Risk Model, and relationship with productive HPV infection. Approximately 50% of oropharyngeal carcinomas (OPC) are mediated by high-risk Human Papillomavirus (HR-HPV), predominantly HPV16/18. It is well-established that patients with HPV-mediated OPC have significantly better outcomes compared with HPV-negative counterparts, despite the fact that these patients present at advanced stage due to lymph node involvement. HPV-mediated cancers typically have an intact p53-proapoptotic pathway, elevated p16 protein, and significantly fewer copy number abnormalities; these features are thought to contribute to the observed improved outcome. However, the mechanisms underlying this observation are under investigation. We hypothesize that HPV oncoproteins diminish local tumor invasiveness and enhance local immune response, thus contributing to improved outcome. This hypothesis stems from observations within the context of the Risk Model, as tumor “pattern of invasion” (POI) and lymphocytic host response are histological model elements. We have generated primary SCC lines from oral and oropharyngeal resections of SCC with different POI phenotypes (aggressive versus nonaggressive POI). Multiple invasion assays confirm that SCC cell lines from specimens with nonaggressive POI (either HPV16+ or HPV-negative), are less invasive than those derived from specimens with aggressive POI (all HPV-negative). We are currently investigating the impact of overexpressing HPV16 E6 and E7 oncoproteins and p16INK4a tumor suppressor protein on HPV-negative cell lines with aggressive pattern of invasion.

Selected Publications 
Publication PUBMEDID
Childs G, Fazzari M, Kung G, Kawachi N, Brandwein-Gensler M, McLemore M, Chen Q, Burk RD, Smith RV, Prystowsky MB, Belbin TJ, Schlecht NF. Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol. 2009; 174:736-45.   2665736 
Li Y, Bai S, Carroll W, Dayan D, Dort JC, Heller K, Jour G, Lau H, Penner C, Prystowsky M, Rosenthal E, Schlecht NF, Smith RV, Urken M, Vered M, Wang B, Wenig B, Negassa A, Brandwein-Gensler M: Validation of the Risk Model: High-Risk Classification and Tumor Pattern of Invasion Predict Outcome for Patients with Low-Stage Oral Squamous Cell Carcinoma. Head Neck Pathol 2012, Dec 19, [Epub ahead of print]  23250819  
Isayeva T, Said-Al-Naif N, Ren Z, Li R, Gnepp D, Brandwein-Gensler M. Salivary Mucoepidermoid Carcinoma: Demonstration of Transcriptionally Active Human Papillomavirus 16/18. Head Neck Pathol 2013, 7: 135-148  23233027 
Bai S, Clubwala R, Adler E, Sarta C, Schiff B, Smith RV, Gnepp D, Brandwein-Gensler M. Salivary Mucoepidermoid Carcinoma: A Multi-institutional Review of 76 patients. Head Neck Pathol 2013, 7: 105-112.  23080318 
Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M. Human Papillomavirus in Non-Oropharyngeal Head and Neck Cancers: A Systematic Literature Review. Head Neck Pathol 2012; 6:S104-S120.   22782230  
Schlecht NF, Brandwein-Gensler M, Smith RV, Kawachi N, Broughel D, Lin J, Keller CE, Reynolds PA, Gunn-Moore FJ, Harris T, Childs G, Belbin TJ, Prystowsky MB. Cytoplasmic Ezrin and Moesin Correlate with Poor Survival in Head and Neck Squamous Cell Carcinoma. Head Neck Pathol 2012; 6:232-243.  22228071 
Lewis JS Jr, Khan RA, Masand RP, Chernock RD, Zhang Q, Al-Naief NS, Muller S, McHugh JB, Prasad ML, Brandwein-Gensler M, Perez-Ordonez B, El-Mofty SK. Recognition of nonkeratinizing morphology in oropharyngeal squamous cell carcinoma - a prospective cohort and interobserver variability study. Histopathology 2012; 60:427-436.  22211374  
Schlecht NF, Brandwein-Gensler M, Nuovo GJ, Li M, Smith RV, Burk RD, Prystowsky MB. A Comparison of Clinically Utilized Human Papillomavirus Detection Methods in Head and Neck Cancer. Modern Pathol 2011; 24:1295-1305.  21572401 
Storck K, Moh'd Hadi U, Simpson R, Ramer M, Brandwein-Gensler M: Sinonasal Renal Cell-Like Adenocarcinoma: A Report on Four Patients. Head and Neck Pathology. 2008; 2:75-80.   20614326 
Lawson W, Schlecht NF, Brandwein-Gensler M: The Role of the Human Papillomavirus in the Pathogenesis of Schneiderian Inverted Papillomas: A Critical Review of the Evidence. Head and Neck Pathology. 2008; 2: 49-59.
 
20614323 
Hunter J, Smith RV, Brandwein-Gensler M:Low-Grade Papillary Adenocarcinoma of the Palate: The Significance of Distinguishing it from Polymorphous Low-Grade Adenocarcinoma. Head and Neck Pathology. 2008; 2:316-324.  20614302 
Belbin TJ, Schlecht N Adrien LA, Kawachi N, Brandwein-Gensler M, Bergman A, Smith RV,Childs G, Prystowsky MP: Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC. Head and Neck Pathology. 2008; 2: 243-256.  20614290 
Lewis JS Jr, Spence DC, Chiosea S, Barnes EL Jr, Brandwein-Gensler M, El-Mofty SK. Large Cell Neuroendocrine Carcinoma of the Larynx: Definition of an Entity. Head Neck Pathol. 2010; 4:198-207.  20589486 
Brandwein-Gensler M, Smith RV, Wang B, Penner C, Theilken A, Broughel D, Schiff B, Owen RP, Smith J, Sarta C, Hebert T, Nason R, Ramer M, DeLacure M, Hirsch D, Myssiorek D, Heller K, Prystowsky M, Schlecht NF, Negassa A. Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma. Am J Surg Pathol. 2010 May;34(5):676-88.  20414102 
McLemore MS, Haigentz M Jr, Smith RV, Nuovo GJ, Alos L, Cardesa A, Brandwein-Gensler M. Head and neck squamous cell carcinomas in HIV-positive patients: a preliminary investigation of viral associations. Head Neck Pathol.
2010; 4:97-105. 
20333562 
Brandwein-Gensler M, Smith RV. Prognostic indicators in head and neck oncology including the new 7th edition of the AJCC staging system. Head Neck Pathol. 2010; 4:53-61.   20237990 
Loudig O, Milova E, Brandwein-Gensler M, Massimi A, Belbin TJ, Childs G, Singer RH, Roahn T, Prystowsky MB: Molecular restoration of archived transcriptional profiles by complementary-template reverse-transcription (CT-RT). Nucleic Acids Res 2007,35:e94.  1976468 
Belbin TJ, Bergman A, Brandwein-Gensler M, Chen Q, Childs G, Garg M, Haigentz M, Hogue-Angeletti R, Moadel R, Negassa A, Owen R, Prystowsky MB, Schiff B, Schlecht NF, Shifteh K, Smith RV, Zheng X: Head and neck cancer: reduce and integrate for optimal outcome. Cytogenet Genome Res.118:92-109, 2007. DOI: 10.1159/000108290  18000360 
Schlecht NF, Burk RD, Adrien L, Dunne A, Kawachi N, Sart C, Chen Q, Brandwein-Gensler M, Prystowsky MB, Childs G, Smith RV, Belbin TJ: Gene expression profiles in human papilloma virus infection infected head and neck cancer. J Pathol.2007; 213:283-293.  17893858 
Teixeira MS, Camacho-Vanegas O, Fernandez Y, Narla G, DiFeo A, Lee B, Kalir T, Friedman SL, Schlecht NF, Genden EM, Urken M, Brandwein-Gensler M, Martignetti JA.KLF6 allelic loss is associated with tumor recurrence and markedly decreased survival in head and neck squamous cell carcinoma.Int J Cancer. 2007; 121:1976-1983.  17621627 
Madan R, Brandwein-Gensler M, Schlecht NF, Elias K, Gorbovitsky E, Belbin TJ, Mahmood R, Breining D, Qian H, Childs G, Locker J, Smith R, Haigentz M Jr, Gunn-Moore F, Prystowsky MB.Differential tissue and subcellular expression of ERM proteins in normal and malignant tissues: cytoplasmic ezrin expression has prognostic signficance for head and neck squamous cell carcinoma.Head Neck. 2006; 28:1018-1027.  16783828 
Adrien LR, Schlecht NF, Kawachi N, Smith RV, Brandwein-Gensler M, Massimi A, Chen S, Prystowsky MB, Childs G, Belbin TJ. Classification of DNA methylation patterns in tumor cell genomes using a CpG island microarray.Cytogenet Genome Res. 2006; 114:16-23.  16717445 
Gnepp DR, Wang LJ, Brandwein-Gensler M, Slootweg P, Gill M, Hille J.Sclerosing polycystic adenosis of the salivary gland: a report of 16 cases.Am J Surg Pathol. 2006; 30:154-164.  16434888 
Gunn-Moore FJ, Welsh GI, Herron LR, Brannigan F, Venkateswarlu K, Gillespie S, Brandwein-Gensler M, Madan R, Tavaré JM, Brophy PJ, Prystowsky MB, Guild S.A novel 4.1 ezrin radixin moesin (FERM)-containing protein, 'Willin'.FEBS Lett. 2005; 579:5089-5094.  16137681 
Teng MS, Brandwein-Gensler MS, Teixeira MS, Martignetti JA, Duffey DC.A study of TRAIL receptors in squamous cell carcinoma of the head and neck.Arch Otolaryngol Head Neck Surg. 2005 May;131(5):407-412.  15897419 
Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, Genden E, Urken ML, Wang BY Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival.Am J Surg Pathol. 2005; 29:167-178.  15644773 
Hinni M, Ferlito A, Brandwein-Gensler M, Takes, RP, Silver CE, Westra WH, Seethala RR, Rodrigo JP, Corry J, Bradford CR, Hunt JL, Strojan P, Devaney KO, Gnepp DR, Hartl DM, Kowalski LP, Rinaldo A, Barnes L. Surgical Margins in Head and Neck Cancer: A Contemporary Review. Head Neck 2012 Sept 3, doi: 10.1002/hed.23110  22941934 

Keywords
Risk Model, squamous carcinoma, head and neck, HPV, immune response