Abstract 5145: The niche architecture and nuclear structure of cancer stem cells

Background: Cell nuclei with fulgen-negative round areas of uniform diameter in the buccal mucosa were first reported by the author in 1962 as reflections of a primary malignant tumor in a distant site as well as in precursor lesions of the uterine cervix. These cells were designated as a malignancy-associated change (MAC). The origin of these cells was unknown. However, recent observations reveal that the nuclear structure of cancer stem cells is identical to MAC cell morphology. The nuclear pattern originally identified as MAC denotes a cancer stem cell at a distance from the primary tumor. Methods: This coincidental finding led to the review of 76 histologic sections of adenomatous colonic polyps, 60 specimens of peripheral blood and 299 buccal mucosal spreads. Evaluation of the cell nuclear structure was made by utilization of the highest microscopic magnification (100x objective, 10x ocular, tube length 1.25). Results: Review of the MAC cases revealed the cancer stem cell microenvironment with asymmetric cell division. The stem cell niche has a well organized but variable micro-environmental architecture depending upon developmental stages within the niche. Self-renewal daughter and progenitor cells were characterized by identical cribriform nuclear structure in fulgen-negative stained and hematoxylin-eosin unstained spherical areas with uniform diameters. These malignancy-associated stem/progenitor cells were identified in 19 of 28 cases of colonic adenomatous polyps with focal carcinoma at sensitivity of 68%, specificity 88%. Peripheral blood cells with identical nuclear pattern were observed as a manifestation of carcinomas of the bladder, kidney and prostate in 23 of 29 cases at sensitivity 79%, specificity 80%. In buccal mucosa specimens an identical nuclear pattern was noted in 112 of 145 cases at sensitivity 77%, specificity 86% as a reflection of tumors in the lung, urogenital and gastrointestinal tract. Discussion: The specific uniform nuclear structure in cells of the colon, peripheral blood and buccal mucosa distant from the primary tumor were identified as cancer stem cells. Self-renewal and progenitor cells in asymmetric division have an identical specific nuclear structure and retain their precise nuclear pattern during their migration and final destination at distant sites. The nuclear-specific structure of these cells permits not only their identification but also their role as a reflection of a primary tumor at a different site. Conclusion: Examination at the highest magnification of the light microscope revealed precise nuclear structure of self-renewal and progenitor cells. Visualization of the cancer stem cell niche architecture and of the stem cell specific nuclear structure offers additional parameters for identification of stem/progenitor cell morphology, migration pathways and detection of cancer manifestation in sites distant from the primary tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5145.