Tan A. Ince, MD, PhD

Effective classification systems allow a deeper understanding of the pathophysiology, diagnosis, and treatment of human cancers. Dr. Ince’s team previously showed that the same oncogenes can produce very different phenotypes in two different breast cells−a finding indicating the importance of cell-of-origin in tumor behavior. Based on this paradigm, Dr. Ince’s team now describes eleven mutually exclusive differentiation states in normal human breast cells. These differentiation states are maintained in breast tumors and are associated with significant differences in patient survival.

For decades, several forms of blood cancers have been successfully classified by exploiting the phenotypic resemblance of tumor cells to specific normal cell counterparts. Similarly, Dr. Ince proposes to show that breast cancers can also be accurately classified by using normal cell differentiation states as an objective reference point. In combination with other relevant information, such as HER2 amplification, he plans to develop a classification scheme that uses normal breast cells as a reference point to provide a stable system to classify human breast tumors.

Mid-year Progress: Research led by Dr. Ince previously showed that some tumor causing oncogenes produce highly malignant tumors in some normal human breast cell types, but not in others. With funds from BCRF these investigators have been trying to understand why some normal human breast cells give rise to more malignant tumors than others. So far, they have describe eleven normal breast cell types in human breast and showed that each breast tumor is similar to one of these normal cell types. Importantly, each normal cell type was associated with significant differences in patient survival. More recently, they discovered that Heat-Shock Factor 1 (HSF1), master regulator of the cellular stress response, is expressed at higher levels in some of these breast cells subtypes, but not in others. Dr. Ince's team found that patients whose tumors contain higher levels of HSF1 have a much worse outcome. They recently published papers that describe these results in scientific journals Proceedings of the National Academy of Science (PNAS) and Cell. Their hope is that this information will lead to better understanding and more precise classification of human breast tumors.

Read more about Dr. Ince's work on HealthCanal.com

Bio:
Dr. Ince is an Associate Professor of Pathology and director of Tumor Stem Cell Division at the Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine. After receiving his MD at Hacettepe University in Ankara, Dr. Ince received a PhD degree in Pharmacology from Cornell University. During this work, he identified a novel DNA binding site for the tumor suppressor protein p53 that regulates human multidrug resistance gene (MDR1), which may contribute to chemotherapy resistance in p53 mutated tumors. Following basic science training at Cornell, he continued his clinical training in Anatomic and Surgical Pathology at Massachusetts General Hospital and completed a subspecialty fellowship in breast and gynecologic pathology at Brigham and Women's Hospital, Harvard Medical School.

Dr. Ince received a career development award from National Cancer Institute for advanced research training in the laboratory of Dr. Robert Weinberg at the Whitehead Institute, Massachusetts Institute of Technology, where he stayed during 2000-07. While at the Whitehead Institute, Dr. Ince developed a new cell culture nutrient medium that is now widely used to grow human breast and ovary cells in the laboratory. This advancement provided the opportunity to directly compare genetically identical tumors that were created from various distinct normal human breast cell types. This work revealed that tumor cell behavior is strongly influenced by the nature of the normal cell type that serves as the precursor of the tumor cells.