Kathy Q. Cai, MD, PhD
Assistant Research Professor
Office Phone: 215-214-3208
Areas of special interests
a. To develop and improve immunohistochemical (IHC; traditional and fluorescence-based) assays to detect and quantify important components of cell signaling pathways.
Automated and quantitative image analysis systems have been widely used in many research fields in recent years. We introduced and applied for the first time at Fox Chase Cancer Center the AQUA (Automated Quantitative) and Aperio IHC quantitation technologies. The AQUA platform, available now at the Biosample Repository, was specifically developed to provide an objective, continuous variable for measuring protein expression in defined regions of formalin-fixed, paraffin-embedded tissue sections using fluorescent light-based quantitative techniques. Aperio image analysis, utilized in the Histopathology Facility, is a chromagen-based/light microscopy system for traditional IHC data acquisition, image analysis and quantitation.
Markers already developed for use with these platforms include but are not limited to: oncogenes, tumorsuppressors, cell signaling pathway markers such as p53, Her-2, EGFR, pAKT, PTEN, pERK, ACK, pACK , pERK, pAurora A; proliferating markers such as Ki-67; cell cycle regulators such as p21, p27, p16, p14, p57; and DNA damage response proteins such as ERCC1, RRMI. See Image 1 and 2.
b. Understanding the molecular mechanism of ovarian cancer initiation and development.
Epithelial ovarian cancer is the leading cause of death from gynecological malignancy among women in developed countries. The high rate of recurrence and mortality of ovarian cancer underscores the need for a greater understanding of the molecular basis of the disease. A dualistic two-pathway model of ovarian tumorigenesis has been proposed based on clinico-pathological and molecular genetic studies. Different pathway cancers have different precursor lesions, molecular characteristics and clinical impacts. High-grade serous ovarian carcinoma (HGSOC), a major subtype of ovarian cancer, was recently suggested to arise from dysplastic tubal epithelium (tubal intraepithelial carcinoma, TIC) and is associated with early mutational loss of TP53. Our preliminary data show strongly staining of p53 (detecting mutant p53) both in areas of TIC and the concurrent ovarian carcinoma (Image 3). In order to address the stages of HGSOC progression, we are using a series of molecular genetic analyses to evaluate concurrent TIC and HGSOC to determine the additional molecular alterations that lead to disease development. Using AQUA technology and/or Aperio image analysis, biomarkers of cancer signaling are being evaluated on ovarian tissue microarrays (TMAs). The data will be statistically analyzed for the association of marker expression and clinicopathological variables and patient survivals. Results from Aperio and AQUA quantitation will be compared. Biomarker studies of ovarian cancer will improve our understanding of ovarian cancer initiation and progression as well as provide tools for better disease management.
Interpretative histopathological supports to FCCC research programs
As a pathologist of the Histopathology Facility, I have the opportunity to collaborate and provide histopathological and immunohistochemical support to numerous in-house research projects.
a. collaboration with Dr. Igor Astsaturov. Dr. Astsaturov is studying the role of C4-demethylating genes in the cholesterol pathway in regulating response of cancer cells to EGFR inhibitors. To support this work, I am performing histopathological evaluation, and immunohistochemistry-based interpretation of skin lesions in bioengineered mice using the Aperio image analysis system to quantitate effects on expression of EGFR and its effectors ERK1/2 and AKT.
b. collaboration with Dr. Jonathan Chernoff. Dr. Chernoff is studying the role of p21-activated kinase 1 (Pak1) during tumor formation and progression of a Ras-mediated skin cancer model. To support this work, I am performing histopathological evaluation, immunohistochemistry, and IHC manual scoring to assess ERk and Akt activity and the tumor proliferation rate, indicated by Ki-67 staining.