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One or more keywords matched the following properties of Fischer, Andrew
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Academic Background:

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

MD, Brown University, Providence, Rhode Island

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

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

Academic Interests:

Cytology is the field that uses the smallest possible biopsy for diagnosis, by identifying structural changes 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).

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 ultrasound-guided STAT FNA Clinic has been started whereby a Cytopathologist performs and immediately interprets the FNA.

I have also been interested in developing technical solutions to the problem of acquiring and processing microsized pieces of tissue for diagnosis. I invented the CellientTM Automated Cell Block System (covered with eight patents), licensed to Hologic Corporation in Marlborough, MA.  CellientTM automatically recovers small tissue fragments from a specimen container and 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, with essentially 100% recovery and no chance for cross contamination during processing. Two other patents relate to automated processing and embedding of larger biopsies.  An improved microbiopsy needle was patented and clinical trials are pending.  Automating rapid onsite assessment of adequacy of microbiopsies is an important goal for Cytology. 

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 bridge the molecular and cellular levels, to learn the biochemical basis and functional significance of diagnostic changes in the structure of cancer cells. My lab has developed the idea that there are predictable relationships between cellular-level structural changes diagnostic of cancer and the genes that are active. In some cases (predictably), cancer genes directly induce the changes diagnostic of the particular cancers associated with the genes.  We have identified 8 different cancer genes with such a relationship to diagnostic cell 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 have been 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. Very likely, but still unproven, these will function very similar to B-RAF V600E in inducing these cellular level diagnostic structural changes.  We have determined the phosphotyrosine docking site on these tyrosine 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. Using cell lines 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, as if chromatin-based forces distorted the nuclear lamina.

The finding of dynamic changes led us to develope a technique for immobilizing living human tissue fragments with mussel-adhesive protein, and performing two-photon microscopy in time lapse.  This live tissue imaging system is amenable to gene editing and therefore offers the potential to model human disease dynamics in vitro.

The paradigm that cancer genes are linked predictably and 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.

 

Cytopathology Fellowship Available-

One position is available for an ACGME-accredited one-year Cytopathology Fellowship. The Fellowship is unique in integrating Cell Biology concepts related to Cytopathology and offering basic research opportunities related to understanding the molecular basis of diagnostic morphologic cellular changes in cancer cells. The program also offers extensive training in performance of ultrasound-guided FNA, and the potential to participate in technology development related to biopsy devices and specimen processing. Candidates must be AP or AP/CP eligible, and preference will be given to candidates interested in participating in ongoing research. The full curriculum includes a strong foundation in classical morphologic diagnosis (125,000 GYN, 10,000 non-GYN per year for the combined Quest-UMASS venture), ultrasound-guided FNA performance and interpretation (about 200 per year), integration of Molecular Pathology and flow cytometry, cytopreparatory methods, and laboratory management. Stipend is determined by years of post-graduate experience. Click here for more information.

 

One or more keywords matched the following items that are connected to Fischer, Andrew
Item TypeName
Academic Article Nuclear structure in cancer cells.
Academic Article Detection of malignancy in cytology specimens using spectral-spatial analysis.
Academic Article Circulating tumor cells: seeing is believing.
Academic Article Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer.
Academic Article Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis.
Academic Article Clinical and pathologic features and clinical impact of false negative thyroid fine-needle aspirations.
Academic Article Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations.
Academic Article Molecular aspects of diagnostic nucleolar and nuclear envelope changes in prostate cancer.
Academic Article Incorporating pathologists' criteria of malignancy into the evolutionary model for cancer development.
Academic Article Cell blocks of breast FNAs frequently allow diagnosis of invasion or histological classification of proliferative changes.
Academic Article Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations.
Academic Article Use of IMP3 in identification of carcinoma in fine needle aspiration biopsies of pancreas.
Academic Article Hemosiderin laden macrophages and hemosiderin within follicular cells distinguish benign follicular lesions from follicular neoplasms.
Academic Article The cytologic criteria of malignancy.
Academic Article Improved preoperative definitive diagnosis of papillary thyroid carcinoma in FNAs prepared with both ThinPrep and conventional smears compared with FNAs prepared with ThinPrep alone.
Academic Article Role of cytology in the management of non-small-cell lung cancer.
Academic Article 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.
Academic Article Five top stories in cytopathology.
Academic Article Catastrophic nuclear envelope collapse in cancer cell micronuclei.
Academic Article Evidence for increasing usage of low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) Pap test interpretations.
Concept Lung Neoplasms
Concept Rectal Neoplasms
Concept Prostatic Neoplasms
Concept Urinary Bladder Neoplasms
Concept Pancreatic Neoplasms
Concept Uterine Cervical Neoplasms
Concept Endometrial Neoplasms
Concept Thyroid Neoplasms
Concept Early Detection of Cancer
Concept Urologic Neoplasms
Concept Neoplasms, Ductal, Lobular, and Medullary
Concept Breast Neoplasms
Concept Neoplasms
Concept Skin Neoplasms
Concept Colonic Neoplasms
Academic Article Melanoma spheroid formation involves laminin-associated vasculogenic mimicry.
Academic Article The diagnostic pathology of the nuclear envelope in human cancers.
Academic Article Cytologic diagnosis of metastatic alveolar rhabdomyosarcoma to the thyroid gland by fine-needle aspiration.
Academic Article Prior high-risk human papillomavirus testing and Papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: results of a retrospective multicenter study.
Academic Article Metastasis-associated MCL1 and P16 copy number alterations dictate resistance to vemurafenib in a BRAFV600E patient-derived papillary thyroid carcinoma preclinical model.
Academic Article Technical and US regulatory issues in triaging material for the molecular laboratory.
Academic Article Causes of false-negative for high-grade urothelial carcinoma in urine cytology.
Academic Article Intranuclear cytoplasmic inclusions are a specific feature of intraductal papillary mucinous neoplasms that distinguish contaminating gastric epithelium.
Academic Article Significance of cytopathologist's review of Pap tests screened as negative for intraepithelial lesion or malignancy that are positive for high-risk human papillomavirus.
Academic Article Cytologic processing of ureteral microbiopsies is associated with higher sensitivity for detection of urothelial carcinoma compared with conventional biopsy processing.
Academic Article Colposcopic endocervical brushing cytology appears to be more sensitive than histologic endocervical curettage for detecting endocervical adenocarcinoma.
Academic Article Cytologically targeted next-generation sequencing: a synergy for diagnosing urothelial carcinoma.
Academic Article Diagnostic value of a comprehensive, urothelial carcinoma-specific next-generation sequencing panel in urine cytology and bladder tumor specimens.
Academic Article Lenvatinib Targets PDGFR-? Pericytes and Inhibits Synergy With Thyroid Carcinoma Cells: Novel Translational Insights.
Academic Article Fluorescence Polarization Imaging of Methylene Blue Facilitates Quantitative Detection of Thyroid Cancer in Single Cells.
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