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HMGA2 is a small, non-histone, chromatin-associated protein with a key role in tumorigenesis and adipogenesis. Indeed, HMGA2 overexpression has been frequently detected in several malignant neoplasms and inhibition of its expression prevents thyroid cell transformation. Moreover, HMGA2 null mice show a pigmy phenotype with a great reduction in fat tissue. To investigate whether HMGA2 expression correlates with clinico-pathological parameters and patient outcome, immunohistochemical analysis of HMGA2 expression was performed in ovarian cancer specimens from 117 patients. HMGA2 overexpression was found in 39% of the cases and, interestingly, positively correlated with the body mass index (BMI). Moreover, high BMI (≥ 25 kg/m(2) ) and high HMGA2 expression/BMI combined evaluation predicted shorter disease-free survival. High BMI (≥ 25 kg/m(2) ), high expression of HMGA2 and high HMGA2 expression/BMI combined evaluation predicted shorter overall survival. In multivariate analysis, the concomitant high expression of HMGA2 and high BMI (≥ 25 kg/m(2) ) was an independent prognostic factor. Finally, the BMI (≥ 25 kg/m(2) ) negatively correlated with the patient response to chemotherapy (P=0.039). Therefore, the data reported herein suggest that the combined evaluation of HMGA2 expression and obesity assessed through BMI can be considered a marker of poor prognosis in patients affected by ovarian carcinoma., (© 2013 Wiley Periodicals, Inc.)

The FEZ1/LZTS1 (FEZ1) gene maps to chromosome 8p22 and is frequently altered in human cancer. FEZ1 has been proposed as a candidate tumour suppressor gene and its loss may contribute to tumour progression. We have analysed the expression of FEZ1 protein in tissues from ovarian carcinomas in relation to clinico-pathological variables, response to chemotherapy and disease-free and overall survival. FEZ1 status was assessed by immunohistochemistry. Cytoplasmic staining for FEZ1 protein was absent or drastically reduced in 38% of tumours. FEZ1 protein expression was not related to tumour grade, histotype, disease-free survival, or overall survival. On the contrary, it was significantly correlated with age and with FIGO stage of disease. This finding indicates that FEZ1 is involved in ovarian carcinogenesis. Moreover, loss of FEZ1 protein significantly predicted a complete treatment response in patients who received taxane-based chemotherapy. In conclusion, the reduction or loss of FEZ1 protein could be an aid to the clinical management of patients affected by ovarian carcinoma., ((c) 2009 Wiley-Liss, Inc.)

HMGI(Y) proteins are overexpressed in experimental and human malignancies, including colon, prostate and thyroid carcinomas. To determine at which step of the carcinogenic process HMGI(Y) induction occurs, we analysed the expression of the HMGI(Y) proteins in hyperplastic, preneoplastic and neoplastic tissues of colorectal origin by immunohistochemistry. All the colorectal carcinomas were HMGI(Y)-positive, whereas no expression was detected in normal colon mucosa tissue. HMGI(Y) expression in adenomas was closely correlated with the degree of cellular atypia. Only 2 of the 18 non-neoplastic polyps tested were HMGI(Y)-positive. These data indicate that HMGI(Y) protein induction is associated with the early stages of neoplastic transformation of colon cells and only rarely with colon cell hyperproliferation., (Copyright 2001 Wiley-Liss, Inc.)

Follicular thyroid adenomas are epithelial tumors characterized by subgroups with specific chromosomal aberrations. Here we present a case with translocation t(1;6)(p35;p21). In 1p35 and 6p21, two genes of the high-mobility group of proteins are located. With P1-derived Artificial Chromosome (PACs) derived from the HMG17 gene located at 1p35 and HMGI(Y) located at 6p21, fluorescence in situ hybridization was performed. The breakpoints were located distal to HMG17 and proximal to HMGI(Y), but no rearrangement of the genes was shown by FISH. However, an overexpression of the HMGI(Y) gene was detected by RT-PCR as well as by immunohistochemistry techniques. This suggests a breakpoint in the proximity of the HMGI(Y) deregulating HMGI(Y) gene expression, a situation found in a variety of human benign mesenchymal tumors with involvement of chromosome band 6p21.

We have earlier shown that expression of the human activated Ki-ras, directed by the rat thyroglobulin (TG) promoter in the thyroid gland of transgenic mice, is able to induce thyroid benign tumors, albeit at low incidence. A likely explantation of our results is that the low levels of exogenous Ki-ras transcripts are not sufficient to induce multifocal tumors in the thyroid gland. We have performed experiments to analyze the effects of a similar construct in vitro upon thyroid-cell proliferation and differentiation. Transfection of FRTL-5 rat thyroid cells with the human Ki-rasval12 fused to the rat TG promoter is rapidly followed by reduced expression of the differentiation markers thyroglobulin, thyroperoxydase and thyrotropin receptor, but not by fully malignant cell transformation. The data reported support the hypothesis that Ki-ras mRNA levels are critical to the process of complete neoplastic transformation of thyroid epithelial differentiated cells in vitro.

We previously reported that galectin-1 gene expression increases up to 100-fold in oncogene-transformed rat thyroid cells compared with their normal counterparts and that the relative mRNA levels correlate with the degree of malignancy. In the present study we investigated whether galectin-1 is differentially expressed in human thyroid neoplasms, which range from well-differentiated tumors to undifferentiated anaplastic carcinomas. We analyzed 74 human thyroid specimens of neoplastic, hyperproliferative and normal tissues and several tumor cell lines. Galectin-1 mRNA and protein levels were higher in 6 thyroid carcinoma-derived cell lines than in normal thyroid primary cultures and adenoma cells. Galectin-1 mRNA levels increased in 28/40 papillary carcinomas and in 6/7 anaplastic carcinomas compared with normal or hyperplastic thyroid. Conversely, galectin-1 expression was unaffected in follicular carcinomas and benign adenomas. Immunohistochemical analysis of normal thyroid and papillary carcinoma sections revealed a higher content of galectin-1 protein in neoplastic follicular cells than in normal cells.