Over-Expression of ßII-Tubulin and Especially Its Localization in Cell Nuclei Correlates with Poorer Outcomes in Colorectal Cancer.

Tubulin is a heterodimer of α and ß subunits, both existing as isotypes differing in amino acid sequence encoded by different genes. Specific isotypes of tubulin have associations with cancer that are not well understood. Previous studies found that ßII-tubulin is expressed in a number of transformed cells and that this isotype is found in cell nuclei in non-microtubule form. The association of ßII expression and its nuclear localization with cancer progression has not previously been addressed. We here used a monoclonal antibody to ßII to examine patients with colorectal cancer and found that patients whose tumors over-express ßII have a greatly decreased life expectancy which is even shorter in those patients with nuclear ßII. Our results suggest that ßII-tubulin may facilitate cancer growth and metastasis and, to accomplish this, may not need to be in microtubule form. Furthermore, ßII expression and localization could be a useful prognostic marker. We also found that ßII appears in the nuclei of otherwise normal cells adjacent to the tumor. It is possible therefore that cancer cells expressing ßII influence nearby cells to do the same and to localize ßII in their nuclei by an as yet uncharacterized regulatory pathway.

Inter- and intra-tumoral relationships between vasculature characteristics, GLUT1 and budding in colorectal carcinoma.

Vascular characteristics, hypoxia and tumor budding are features that have been implied in the biology and prognosis of colorectal cancer. Internal relationships and the inter- and intra-tumoral variation of these tumor properties remain to be determined. In the current study we have characterized blood vessel status in different areas of CRC and in the peritumoral fibroblastic stroma. Analyses of these characteristics have been supplemented by characterization of budding and hypoxia. Analyses revealed significantly lower values of vessel perimeter (VP) and vessel lumen area (VL) at the invasive front and surrounding stroma as compared to the tumor center. Also, the number of vessels (VN) in the peritumoral stroma was higher than in the center. Thus, tumor center displays larger and fewer vessels as compared to the tumor periphery. GLUT1 expression was correlated directly with VN (r=0.351, p=0.028) and inversely with VL and VP (r=-0.432, p=0.006 and r=-0.484, p=0.002) at the invasive front. Moreover, GLUT1 expression, VP at the invasive front, and VN in the surrounding peritumoral stroma, were associated with budding score (r=0.574, p<0.000, r=-0.340, p=0,034 and r=-0.389, p=0.025 respectively). Furthermore, GLUT1, budding score, vessel number in peritumoral stroma, and vessel size in the invasive front, were significantly different in tumors with or without lymph node metastasis. This study reports previously unrecognized relationships between localization-specific vascular characteristics, hypoxia and tumor budding. The findings suggest potential functional relationships, which should be further explored, and also highlight the inter-tumoral variations in vasculature, which is highly relevant for ongoing efforts to identify vessel-based biomarkers.

Analysis of thyroid malignant pathologic findings identified during 3 rounds of screening (1997-2008) of a cohort of children and adolescents from belarus exposed to radioiodines after the Chernobyl accident.

BACKGROUND: Recent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear. METHODS: A cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression. RESULTS: In total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1; <1%). Higher I-131 doses were associated with higher frequency of solid and diffuse sclerosing variants of thyroid cancer (P < .01) and histologic features of cancer aggressiveness, such as lymphatic vessel invasion, intrathyroidal infiltration, and multifocality (all P < .03). Latency was not correlated with radiation dose. Fifty-two patients with self-reported thyroid cancers which were diagnosed before 1997 were younger at the time of the accident and had a higher percentage of solid variant cancers compared with patients who had screening-detected thyroid cancers (all P < .0001). CONCLUSIONS: I-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness.