Our group has previously determined the relevance of the surface markers CD24 and CD44, and the metabolic marker ALDH as defining the most tumorigenic subpopulations within head and neck squamous cell cancers (HNSCC), also defined as tumor initiating cells or cancer stem cells (CSC). In preclinical models we have shown these CSC markers are associated with worse outcome and resistance to therapy. We have characterized molecularly these subpopulations and have found a distinct molecular signature/profile profile of positive versus negative groups; highly tumorigenic CSC had higher PI3K and Notch/Wnt signaling. This implies that tumors may require different therapy depending on their CSC profile, but before moving forward and proposing clinical trials with specific inhibitorsthese preclinical observations need to be substantiated using clinical samples with long term outcome data. In this project we will determine the distribution of CD24, CD44, and ALDH subgroups using a 500-patient HNSCC retrospective tumor bank with up to 25 years of follow up. We will correlate CSC presence and distribution with tumor staging, tumor location, response to radiation/chemotherapy, as well as with overall survival and cure rates. Relevant signaling pathways associated with CSC, such as the PI3K or Notch/Wnt pathways, will be assessed in subgroups as warranted by the results. The candidate will coordinate the immunohistochemistry staining of the already collected samples, liaise with the HNSCC Program Pathologist, compile and analyze the data, prepare and present the report, as well as lead the writing of the resulting manuscript or sections of manuscript(s).