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Clinical Cytology and Signal

Transduction Dysregulation

a Translational Approach

Mark J. Roth, M.D.

Cytology Section

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Expertise and Methods

Areas of Expertise

Cytopathology

Epidemiologic study principles and design

Molecular diagnostic and translational analysis

Technologies and methods used Light microscopy

Other technologies in collaboration with intramural and

extramural investigators

NanoString nCounter gene expression Analysis system

Microdissection technologies

Immunocytochemistry

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Clinical Cytology and

Signal Transduction Dysregulation

Malignant Mesothelioma, H+E

Malignant Mesothelioma,

Calretinin for xMD targeting

Cytology is a cost effective, minimally invasive approach for

diagnosis and screening. However, lesions that showminimal cytomorphologic and architectural

atypia, such as Malignant Mesothelioma and

Low-grade papillary urothelial carcinoma, can be

challenging and lead to more costly and less timely

diagnostic interventions.

Fortunately, these lesions are often associated with

significant kinase dysregulation.

Consequently, expression analysis may not only enhance

our diagnostic sensitivity, but could have therapeutic

implications.

In collaboration with the Molecular Diagnostics section, initial

efforts will include a NanoString nCounter multiplex

platform analysis to explore 519 human kinases.

In collaboration with the Pathogenetics unit, the latest

microdissection techniques e.g., xMD, will be incorporated,

to more specifically characterize the neoplastic

and non-neoplastic (e.g. inflammatory) elements.

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Research Implications

These efforts directly support the research mission of theLP, the NCI and the NIH by investigating the biology and

genetics of disease and developing and applying leading

edge technology to diagnostic pathology.

This collaborative research will translate into potential

clinical applications by uniquely and more accurately

characterizing reactive and neoplastic processes in

routine clinical samples.

This information will have direct patient care implications including:

Enhancing the diagnostic utility of routine, minimally invasive cytology

samples

Identifying and monitoring therapeutic targets such as tyrosine

kinases

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Future Directions

High throughput profiling of clinical cytology

samples

Diagnostic tool

Therapeutic monitoring and targeting

Enhanced biological understanding

Challenges and Obstacles

Reagents: including but not limited to biochemical

analytes and the resources for fresh recuts from

cytology paraffin blocks

Bioinformatic support

IRB approval for non-anonymized samples

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Collaborators

Members of the following LPsections/units:

Cytopathology

Anatomic

Molecular Diagnostics and

Immunohistochemical

Pathogenetics

Surgery Branch