The Division of Anatomic Pathology has a proud record in translational and clinical research . Our 20 faculty members have created a research community that engages in diverse investigations to discover and study novel molecular biomarkers across patient populations suffering from various malignancies. Particular emphasis is placed on molecular epidemiology studies to establish biomarkers directly applicable to clinical practice to enhance patient care in areas of disease diagnosis, treatment, and prevention. For example, Dr. Zhong Jiang discovered and established the use of the P504 (AMACR) marker for the diagnosis of prostate cancer in 2001. This biomarker has since become part of routine tests in diagnosing prostate cancer by pathologists internationally. The collective efforts of our faculty members have generated many nationally well-known findings and publications in high-ranking scientific journals .
As part of the commitment from the Department of Pathology, the faculty of the Division enjoy a 600 square feet on-site research facility and two full-time highly experienced research technologists. Modern research techniques are available for use, including laser-capturing microscopy, tissue array techniques, FISH, automated processing and automated imaging processing, multicolor quantitative PCR, four-color capillary gel electrophoresis, Luminex liquid bead microarray analysis of microRNA, and Immunohistochemistry.
Pathology residents in training benefit from the research environment and are encouraged to participate in projects. Every year, their work is well represented in national meetings. In year 2009, our Division ranked in the top 10% of departments in number of abstracts presented at USCAP meeting among all institutions.
The following are some of our on-going research activities:
Studies on the prognostic value of biomarker, IMP3, in many malignant tumors:
Insulin-like growth factor-II mRNA binding protein 3 (IMP3) is a RNA binding protein involved in mRNA localization and translation. It is normally expressed only during embryogenesis. Dr. Jiang and his colleagues have found that some renal cell carcinomas express IMP3, and the expression of IMP3 predicts poor outcome independent of tumor staging and other factors. Testing for IMP3 expression is now a part of standard clinical care in our institution. Currently, several of our faculty members are investigating the prognostic value of IMP3 in a number of other malignancies, including urothelial carcinomas, endometrial carcinoma, and meningioma.
Searching for molecular markers that predict progression of cervical cancer precursors:
It has long been known that the vast majority of cervical cancer precursors are reversible. Only the irreversible precursors need surgical treatment. Dr. Lu and his colleagues are working to find ways to identify those irreversible precursors. Our studies evaluating the biomarker, IMP3, for this purpose is almost complete after the analysis of more than 1300 lesions. Currently, cDNA array and microRNA array studies are under way. Success of these studies will significantly impact cervical cancer prevention.
Endometrial cancer studies:
Screening for endometrial cancer is very difficult, as it requires invasive procedures, such as endometrial biopsy and curettage. Dr. Fischer and his colleagues are currently working on a project to evaluate the use of endometrial brushing technique for endometrial cancer screening. Additionally, since many endometrial lesions, especially the atypical complex hyperplasia, are difficult to diagnose by conventional histology, Dr. Lu and his colleagues are searching for biomarkers that will further clarify these lesions and establish more meaningful diagnosis.
Molecular diagnosis of solid tumors:
Molecular diagnosis of solid tumors is at the forefront of pathology research. The Division is using cutting edge technology to develop molecular diagnosis of such tumors. Drs. Cosar and Hutchinson are currently applying automated processing and automated imaging processing for FISH analysis of urothelial carcinomas, particularly for low-grade carcinomas that can not be diagnosed reliably by cytology. Other studies underway include improved molecular evaluation of Her2/neu expression by breast cancer cells, and accelerated and cost-effective genetic risk stratification in acute leukemia using spectrally addressable liquid bead microarrays.
Jiang, Z., Chu, P.G., Wu, C.L., Woda, B.A., Rock, K.L., Liu, Q., Balaji, K.C. Combination of Quantitative IMP3 and Tumor Stage (QITS): A new system to predict metastasis for patients with localized renal cell carcinomas. In press, Clinical Cancer Research.
Tang, G., Truong, F., Fadare, O., Woda, B.A., Wang, S.A. Diagnostic Challenges Related to Myeloid/Natural Killer Cells, a Variant of Myeloblasts. Int J Clin Exp Pathol 2008.
King, M., Pearson, T., Shultz, L.D., Leif, J., Bottino, R., Trucco, M. Atkinson, M.A., Wasserfall, C., Herold K.C., Woodland,R.T., Schmidt, M.R., Woda, B.A., Thompson, M.J., Rossini, A.A., Greiner, D.L. A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene. Clin Immunol 126:303-314, 2008.
Sitnikova, L., Mendese, G., Liu, Q., Woda, B.A., Lu, D., Dresser, K., Mohanty, S., Rock, K.L., Jiang, Z. IMP3 Predicts Aggressive Superficial Urothelial Carcinoma of the Bladder. Clin Cancer Res 15:1701-1706, 2008.
Stachurski, D., Smith, B.R., Pozdnyakova, O., Andersen, M., Xiao, Z., Raza, A., Woda, B.A., Wang, S.A. Flow cytometric analysis of myelomonocytic cells by a pattern recognition approach is sensitive and specific in diagnosing myelodysplastic syndrome and related marrow diseases: emphasis on a global evaluation and recognition of diagnostic pitfalls. Leuk Res, 32:215-224, 2008.
Yue, G., Hao, S., Fadare O, Baker, S., Pozdnyakova, O., Galili, N., Woda, B.A., Raza, A., Wang, S.A. Hypocellularity in myelodysplastic syndrome is an independent factor which predicts a favorable outcome. Leuk Res, 32:553-558, 2008.
Jiang Z, Lohse CM, Chu PG, Wu CL, Woda BA, Rock KL, and Kwon ED: The oncofetal protein IMP3: a novel molecular marker that predicts metastasis of papillary and chromophobe renal cell carcinomas. Cancer, 2008, 112:2676-2682
Hoffmann NE, Sheinin Y, Lohse CM, Cheville JC, Parker AS, Leibovich BC, Jiang Z, and Kwon ED: External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma, Cancer, 2008, 112:1471-79
Zheng WX, Yi XF, Fadare O, Liang SX, Martel M, Schwartz PE, and Jiang Z:The oncofetal protein IMP3: A novel biomarker for endometrial serous carcinoma. Am J Surg Pathol, 2008, 32: 304-15
Pozdnyakova O, Stachurski D, Hutchinson L, Ramakrishnan S , Minehart Miron, P. Trisomy 8 in and B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet. 2008 May;183(1):49-52.
Cerny J, Fadare O, Hutchinson L, Wang SA. Clinicopathological Features of Extramedullary Recurrence/Relapse of Multiple Myeloma. Eur J Haematol. 2008 Jul;81(1):65-9. Epub 2008 May 6.
Lu S, Simin K, Khan A, Mercurio A. Analysis of Integrin b4 Expression in Human Breast Cancer: Association with basal-like tumors and prognostic significance. Clin Cancer Res. 2008;14(4):1050-58