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Andrew H Fischer MD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentPathology
AddressUniversity of Massachusetts Medical School
One Innovation Drive, Biotech Three
Worcester MA 01605
Phone508-856-6435
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentPathology
    DivisionAnatomic Pathology

    InstitutionUMMS - School of Medicine
    DepartmentRadiology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentCell Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentClinical Population Health Research


    Collapse Biography 
    Collapse education and training
    Cornell University, Ithaca, NY, United StatesBSCell Biology
    Brown University Alpert Medical School, Providence, RI, United StatesMD

    Collapse Overview 
    Collapse overview

    Academic Background:

    BS (Cell Biology), 1979, Cornell University, Ithaca, NY

    MD, 1984, Brown University, Providence, Rhode Island

    Resident, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 1984-1988

    Cytopathology Fellow with Prabodh Gupta, Hospital of the University of Pennsylvania, Philadelphia, PA 1988-1989

    Cytopathology Fellowship Available-

    One position is availablefor an ACGME-accredited one-year Cytopathology Fellowship. The Fellowship is unique in integrating Cell Biology concepts related to Cytopathology, and offering basic research opportunities directly related to Cell Biology and Cytopathology into the year. Candidates must be AP or AP/CP eligible, and preference will be given to candidates interested in participating in ongoing research relating to the molecular basis of diagnostic morphologic cellular changes in cancer. The full curriculum includes a strong foundation in classical morphologic diagnosis (75,000 GYN, 10,000 non-GYN per year), FNA performance and interpretation (total 2000 FNA's per year), integration of Molecular Pathology and flow cytometry, cytopreparatory methods, and laboratory management. Stipend is determined by years of post-graduate experience. Clickherefor more information.

    Academic Interests:

    Cytology is the field that uses the smallest possible biopsy for diagnosis, by identifying structuralchanges in cells and small tissue fragments. My basic research interest has been to try to define diagnostic structural changes in molecular terms (see Basic Science Research Interest below).Dr. Fischer's picture

    My clinical interest is fine needle aspiration (FNA) biopsy. FNAs are minimally invasive, safe, rapid, and relatively painless means of definitive diagnosis. Having performed over 2,500 FNAs in my career so far, a UMASS FNA Clinic has been started whereby a Cytopathologist performs and immediately interprets the FNA. It is more efficient for cytopathologists to perform the biopsy that they diagnose.

    I have also been interested in developing technical solutions to the problem of acquiring and processing microsized pieces of tissue for diagnosis. Through grants from the Department of Pathology and the University of Massachusetts, I invented the CellientTM Automated Cell Block System (US Patents 6,913,921 and 7,541,161, with three other pending patents). Licensed to Hologic Corporation in Marlborough, MA, CellientTM automatically recovers small tissue fragments from a specimen container and rapidly delivers them to an indexable plane in paraffin for histologic sectioning, in under one hour. CellientTM allows fine needle (22-25 guage) biopsies to be examined in essentially the same manner as much larger core biopsies. Several other invention disclosures to the Office of Technology Management at UMASS have been made relating to improving microbiopsy needles, assessing the quality of a microbiopsy sample at the bedside, and developing automated means of processing and embedding histology samples.

    As criteria become defined at a molecular level, and techniques for procuring and handling micro-sized biopsies are developed, most cancers can be diagnosed with minimally invasive, rapid, and safe cytologic techniques.

    Basic Science Research Interests:

    In spite of years of progress in cancer research, the diagnosis of cancer still generally requires a pathologist to examine a biopsy by light microscopy. Cytopathologists are experts at recognizing changes in cell structure that are diagnostic of various cancers. Surprisingly, cancer researchers still know very little about how or why cancer cells are structured differently from normal cells.My long term goal is to learn the biochemical basis and functional significance of diagnostic changes in the nuclear structure of cancer cells. My lab has developed the idea that cellular-level structural changes diagnostic of cancer are directly caused by the particular cancer genes active in that cancer. We have linked 8 different cancer genes to large scale cellular structural changes, involving chromatin and the nuclear envelope, characteristic of different types of cancers. We think that the structural changes oncogenes induce during their activation provide an essential insight into the functional changes that occur during carcinogenesis.

    Nuclear envelope irregularity and changes in large-scale chromatin organization are important diagnostic alterations in many forms of cancer. We are focused on a pair of tyrosine kinases—RET/PTC and TRK/PTC—that induce the nuclear envelope irregularity and chromatin dispersal diagnostic of papillary thyroid carcinoma. We have determined the phosphotyrosine docking site on these kinases that mediates these changes. We showed that the nuclear lamina composition is very similar between papillary thyroid carcinomas and normal thyroid, and histone composition at a global level is not apparently altered for H3K4m, H3K9m, H3K9/14Ac, and H3K27m. Using micro-injection of RET/PTC into normal thyroid cells in culture, we showed that nuclear envelope irregularity develops during interphase, without an intervening post-mitotic nuclear envelope reassembly, because the nuclear envelope is distorted actively during interphase by forces exerted on it from the cytoskeleton and/or chromatin. More recently, we confirmed that there are active interphase deflections of the nuclear lamina in prostate cancer, and we found that depolymerization of actin or microtubules does not inhibit these dynamics. My lab is interested in developing live cell imaging techniques that can be applied to organ cultures to study the dynamics of nuclear lamina alterations in cancer cells and dependence of lamina dynamics on cell cycle phase or active transcription.

    The paradigm that cancer genes are linked very directly to diagnostic cell structural changes should lead to improved diagnosis of cancer, insight into novel cell physiologies involving chromatin and the nuclear envelope, and a basis for a large-scale screen for novel anticancer drugs.Live cell imaging techniques seem likely to expose new sets of dynamic structural changes with a diagnostic utility surpassing that of classical static imaging.




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Sheridan TB, Walavalkar V, Yates JK, Owens CL, Fischer AH. Cytologic processing of ureteral microbiopsies is associated with higher sensitivity for detection of urothelial carcinoma compared with conventional biopsy processing. J Am Soc Cytopathol. 2019 Aug 08. PMID: 31564532.
      View in: PubMed
    2. Fischer AH. New quantitative data on cell blocks. J Am Soc Cytopathol. 2019 Mar - Apr; 8(2):49-51. PMID: 31287419.
      View in: PubMed
    3. Schmolze DB, Fischer AH. An Automatable Method for Determining Adequacy of Thyroid Fine-Needle Aspiration Samples. Arch Pathol Lab Med. 2018 Oct 24. PMID: 30354272.
      View in: PubMed
    4. Lee PJ, Owens CL, Lithgow MY, Jiang Z, Fischer AH. Causes of false-negative for high-grade urothelial carcinoma in urine cytology. Diagn Cytopathol. 2016 Dec; 44(12):994-999. PMID: 27781412.
      View in: PubMed
    5. Fischer AH, Hutchinson LM. Technical and US regulatory issues in triaging material for the molecular laboratory. Cancer Cytopathol. 2016 Sep 6. PMID: 27598019.
      View in: PubMed
    6. Duquette M, Sadow PM, Husain A, Sims JN, Antonello ZA, Fischer AH, Song C, Castellanos-Rizaldos E, Makrigiorgos GM, Kurebayashi J, Nose V, Van Hummelen P, Bronson RT, Vinco M, Giordano TJ, Dias-Santagata D, Pandolfi PP, Nucera C. Metastasis-associated MCL1 and P16 copy number alterations dictate resistance to vemurafenib in a BRAFV600E patient-derived papillary thyroid carcinoma preclinical model. Oncotarget. 2015 Dec 15; 6(40):42445-67. PMID: 26636651.
      View in: PubMed
    7. Walavalkar V, Fischer AH, Owens CL. Significance of cytopathologist's review of Pap tests screened as negative for intraepithelial lesion or malignancy that are positive for high-risk human papillomavirus. J Am Soc Cytopathol. 2015 Jul - Aug; 4(4):190-194. PMID: 31051753.
      View in: PubMed
    8. Walavalkar V, Patwardhan RV, Owens CL, Lithgow M, Wang X, Akalin A, Nompleggi DJ, Zivny J, Wassef W, Marshall C, Levey J, Walter O, Fischer AH. Utility of liquid-based cytologic examination of distal esophageal brushings in the management of Barrett esophagus: a prospective study of 45 cases. J Am Soc Cytopathol. 2015 May - Jun; 4(3):113-121. PMID: 31051691.
      View in: PubMed
    9. Fischer AH, Schwartz MR, Moriarty AT, Wilbur DC, Souers R, Fatheree L, Booth CN, Clayton AC, Kurtyz DF, Padmanabhan V, Crothers BA. Immunohistochemistry practices of cytopathology laboratories: a survey of participants in the College of American Pathologists Nongynecologic Cytopathology Education Program. Arch Pathol Lab Med. 2014 Sep; 138(9):1167-72. PMID: 24840035.
      View in: PubMed
    10. Zhao C, Li Z, Nayar R, Levi AW, Winkler BA, Moriarty AT, Barkan GA, Rao J, Miller F, Fan F, Zhou Z, Si Q, Fischer AH, Sturgis CD, Jing X, Marshall CB, Witt BL, Birdsong GG, Crothers BA. Prior high-risk human papillomavirus testing and Papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: results of a retrospective multicenter study. Arch Pathol Lab Med. 2015 Feb; 139(2):184-8. PMID: 24694342.
      View in: PubMed
    11. Walavalkar V, Fischer AH, Owens CL. Cytologic diagnosis of metastatic alveolar rhabdomyosarcoma to the thyroid gland by fine-needle aspiration. Acta Cytol. 2014; 58(3):288-92. PMID: 24513670.
      View in: PubMed
    12. Fischer AH. The diagnostic pathology of the nuclear envelope in human cancers. Adv Exp Med Biol. 2014; 773:49-75. PMID: 24563343.
      View in: PubMed
    13. Larson AR, Lee CW, Lezcano C, Zhan Q, Huang J, Fischer AH, Murphy GF. Melanoma spheroid formation involves laminin-associated vasculogenic mimicry. Am J Pathol. 2014 Jan; 184(1):71-8. PMID: 24332013.
      View in: PubMed
    14. Lee PJ, Owens CL, Hutchinson L, Fischer AH. Intranuclear cytoplasmic inclusions are a specific feature of intraductal papillary mucinous neoplasms that distinguish contaminating gastric epithelium. J Am Soc Cytopathol. 2014 Mar - Apr; 3(2):108-113. PMID: 31051700.
      View in: PubMed
    15. Walavalkar V, Tommet D, Fischer AH, Liu Y, Papa DM, Owens CL. Evidence for increasing usage of low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) Pap test interpretations. Cancer Cytopathol. 2014 Feb; 122(2):123-7. PMID: 23983192.
      View in: PubMed
    16. Hatch EM, Fischer AH, Deerinck TJ, Hetzer MW. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell. 2013 Jul 3; 154(1):47-60. PMID: 23827674.
      View in: PubMed
    17. Fischer AH, Benedict CC, Amrikachi M. Five top stories in cytopathology. Arch Pathol Lab Med. 2013 Jul; 137(7):894-906. PMID: 23808461.
      View in: PubMed
    18. Moriarty AT, Bentz JS, Winkler B, Fischer AH, Laucirica R, Souers RJ, Thomas N, Zhao C. The College of American Pathologists' first 3 years' experience with high-risk human papillomavirus proficiency testing for cytology and other laboratories. Arch Pathol Lab Med. 2013 May; 137(5):606-9. PMID: 23627450.
      View in: PubMed
    19. Fischer AH, Clayton AC, Bentz JS, Wasserman PG, Henry MR, Souers RJ, Moriarty AT. Performance differences between conventional smears and liquid-based preparations of thyroid fine-needle aspiration samples: analysis of 47,076 responses in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. Arch Pathol Lab Med. 2013 Jan; 137(1):26-31. PMID: 23276172.
      View in: PubMed
    20. Jean-Gilles J, Fischer AH, Luu MH, Owens CL. Clinical and pathologic features and clinical impact of false negative thyroid fine-needle aspirations. Cancer Cytopathol. 2012 Oct 25; 120(5):326-33. PMID: 22528560.
      View in: PubMed
    21. Luu MH, Fischer AH, Stockl TJ, Pisharodi L, Owens CL. Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis. Acta Cytol. 2011; 55(6):526-30. PMID: 22156461.
      View in: PubMed
    22. Paull PE, Hyatt BJ, Wassef W, Fischer AH. Confocal laser endomicroscopy: a primer for pathologists. Arch Pathol Lab Med. 2011 Oct; 135(10):1343-8. PMID: 21970490.
      View in: PubMed
    23. Fischer AH, Cibas ES, Howell LP, Kurian EM, Laucirica R, Moriarty AT, Renshaw AA, Zakowski MF, Young NA. Role of cytology in the management of non-small-cell lung cancer. J Clin Oncol. 2011 Aug 20; 29(24):3331-2; author reply 3332-3. PMID: 21768461.
      View in: PubMed
    24. Nucera C, Nehs MA, Nagarkatti SS, Sadow PM, Mekel M, Fischer AH, Lin PS, Bollag GE, Lawler J, Hodin RA, Parangi S. Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer. Oncologist. 2011; 16(3):296-309. PMID: 21355020.
      View in: PubMed
    25. Schmolze DB, Standley C, Fogarty KE, Fischer AH. Advances in microscopy techniques. Arch Pathol Lab Med. 2011 Feb; 135(2):255-63. PMID: 21284447.
      View in: PubMed
    26. Luu MH, Fischer AH, Pisharodi L, Owens CL. Improved preoperative definitive diagnosis of papillary thyroid carcinoma in FNAs prepared with both ThinPrep and conventional smears compared with FNAs prepared with ThinPrep alone. Cancer Cytopathol. 2011 Feb 25; 119(1):68-73. PMID: 21140483.
      View in: PubMed
    27. Fischer AH, Zhao C, Li QK, Gustafson KS, Eltoum IE, Tambouret R, Benstein B, Savaloja LC, Kulesza P. The cytologic criteria of malignancy. J Cell Biochem. 2010 Jul 1; 110(4):795-811. PMID: 20564180.
      View in: PubMed
    28. Fischer AH. Circulating tumor cells: seeing is believing. Arch Pathol Lab Med. 2009 Sep; 133(9):1367-9. PMID: 19722740.
      View in: PubMed
    29. Jaffar R, Mohanty SK, Khan A, Fischer AH. Hemosiderin laden macrophages and hemosiderin within follicular cells distinguish benign follicular lesions from follicular neoplasms. Cytojournal. 2009; 6:3. PMID: 19495407.
      View in: PubMed
    30. Yantiss RK, Cosar E, Fischer AH. Use of IMP3 in identification of carcinoma in fine needle aspiration biopsies of pancreas. Acta Cytol. 2008 Mar-Apr; 52(2):133-8. PMID: 18499984.
      View in: PubMed
    31. Li C, Zota V, Woda BA, Rock KL, Fraire AE, Jiang Z, Lu D, Xu B, Dresser K, Lutman CV, Fischer AH. Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations. Mod Pathol. 2007 Dec; 20(12):1263-8. PMID: 17885673.
      View in: PubMed
    32. Istvanic S, Fischer AH, Banner BF, Eaton DM, Larkin AC, Khan A. Cell blocks of breast FNAs frequently allow diagnosis of invasion or histological classification of proliferative changes. Diagn Cytopathol. 2007 May; 35(5):263-9. PMID: 17427225.
      View in: PubMed
    33. Underwood JM, Imbalzano KM, Weaver VM, Fischer AH, Imbalzano AN, Nickerson JA. The ultrastructure of MCF-10A acini. J Cell Physiol. 2006 Jul; 208(1):141-8. PMID: 16607610.
      View in: PubMed
    34. Angeletti C, Harvey NR, Khomitch V, Fischer AH, Levenson RM, Rimm DL. Detection of malignancy in cytology specimens using spectral-spatial analysis. Lab Invest. 2005 Dec; 85(12):1555-64. PMID: 16200074.
      View in: PubMed
    35. Hill DA, Chiosea S, Jamaluddin S, Roy K, Fischer AH, Boyd DD, Nickerson JA, Imbalzano AN. Inducible changes in cell size and attachment area due to expression of a mutant SWI/SNF chromatin remodeling enzyme. J Cell Sci. 2004 Nov 15; 117(Pt 24):5847-54. PMID: 15537831.
      View in: PubMed
    36. Zink D, Fischer AH, Nickerson JA. Nuclear structure in cancer cells. Nat Rev Cancer. 2004 Sep; 4(9):677-87. PMID: 15343274.
      View in: PubMed
    37. Fischer AH, Young KA, DeLellis RA. Incorporating pathologists' criteria of malignancy into the evolutionary model for cancer development. J Cell Biochem. 2004 Sep 1; 93(1):28-36. PMID: 15352159.
      View in: PubMed
    38. Fischer AH, Bardarov S, Jiang Z. Molecular aspects of diagnostic nucleolar and nuclear envelope changes in prostate cancer. J Cell Biochem. 2004 Jan 1; 91(1):170-84. PMID: 14689589.
      View in: PubMed
    39. Fischer AH, Taysavang P, Jhiang SM. Nuclear envelope irregularity is induced by RET/PTC during interphase. Am J Pathol. 2003 Sep; 163(3):1091-100. PMID: 12937150.
      View in: PubMed
    40. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol. 2003 Jul; 120(1):71-7. PMID: 12866375.
      View in: PubMed
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