The first crucial step in cancer management is to assure timely and accurate pathological diagnoses. Formalin fixation and paraffin embedding (FFPE) has been a standard tissue preservation method employed in over 90% cases for clinical histology diagnosis. Though it provides superior morphology and easy long- term storage of clinical specimens, FFPE is time-consuming and does not fully support current molecular analyses. The long-term goal of our research is to apply modern techniques to medical practice and pathological diagnosis to effectively fight cancers and other diseases. Our proposed project is to further develop the ultrasound-accelerated tissue preservation (UTP) technology for multiple tissues and to study the mechanism of ultrasound (US)-facilitated formalin fixation.
Our specific aims are: (1) to develop a multi- tissue preservation processor with an optional real-time digital system to monitor and standardize tissue fixation level; (2)to validate the UTP techniques by performing more statistical assessments on histopathology, macromolecule integrity, and their long-term stability; and (3) to conduct mechanism studies to elucidate the effects of formalin fixation with and without US on the formation of cross-linking, enzymatic activity, and protein conformational changes. We have demonstrated that in comparison to conventional FFPE, UTP provides similar preservation in tissue morphology with similar long-term storage stability, improved preservation of protein structure, antigen properties, and mRNA integrity. UTP allows easy general molecular profiling and analyses based on extracts from UTP-fixed tissues. UTP also provides a good opportunity to control and monitor fixation level by adjusting the time and strength of the ultrasound. We hypothesize that US-facilitated formalin fixation will greatly accelerate formaldehyde-induced macromolecule cross-linking in tissues and """"""""freeze"""""""" macromolecules and their conformation due to accelerated fixation reactions. Since tissue preservation is still a standard and general requirement before histology diagnosis, the innovation should have great impact in economy and public health. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA091166-04
Application #
7280481
Study Section
Special Emphasis Panel (ZCA1-SRRB-U (J1))
Program Officer
Chuaqui, Rodrigo F
Project Start
2001-04-01
Project End
2009-07-31
Budget Start
2007-09-06
Budget End
2008-07-31
Support Year
4
Fiscal Year
2007
Total Cost
$204,117
Indirect Cost
Name
American Registry of Pathology, Inc.
Department
Type
DUNS #
114400633
City
Washington
State
DC
Country
United States
Zip Code
20306
Zou, N; Liang, Q; He, H et al. (2011) Ultrasound-facilitated formalin fixation of biological specimens. Biotech Histochem 86:413-20