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β-Thymosins are structurally related, highly conserved acidic polypeptides, originally isolated from calf thymus. We have recently shown that the TB10 gene is overexpressed in human thyroid carcinoma cell lines and tissues, particularly in undifferentiated thyroid carcinomas, but expressed at an undetectable level in normal thyroid cells. The precise role of thymosin β-10 (TB10) activity in maintaining the malignant phenotype of thyroid cell lines is unknown. To investigate TB10 function and relevance in a model system we used an antisense methodology to suppress TB10 protein synthesis in two human thyroid carcinoma cell lines (NPA and ARO). The growth in soft agar of NPA and ARO cells carrying a TB10 construct in an antisense orientation was significantly reduced. Conversely, anchorage-dependent growth was unchanged in NPA and ARO cells carrying the TB10 construct in a sense orientation or carrying the backbone vector. TB10 expression also affected actin organization. In fact, stress fibers were long and thick in ARO cells in which TB10 expression was suppressed by the antisense construct. Conversely, they were scarce and short in the vector-transfected ARO cells. These data suggest that TB10 plays a critical role in the regulation of anchorage-independent growth and assembly of actin filaments.

Noninvasive thyroid nodules that exhibit borderline morphological signs of papillary cancer are difficult to diagnose and we do not know if they represent papillary carcinoma precursor lesions. Forty-six such nodules were analyzed for RET activation by immunohistochemistry and, in selected cases, by reverse transcriptase-polymerase chain reaction performed on RNA extracted after laser capture microdissection (LCM) of the tumor foci with and without papillary carcinoma features and positive RET immunoreactivity. RET immunoreactivity was identified, at least focally, in 30 of 46 (65.2%) of the nodules where it closely paralleled the morphological changes. Enough RNA was obtained after LCM in seven samples. RET/PTC1 or RET/PTC3 were detected in microscopic foci with papillary carcinoma features in most of the thyroid nodules (five of seven cases). No RET/PTC1 or RET/PTC3 rearrangements were detected in areas of the same tumors that lacked the cytological alterations. Analysis of clonality in the same nodules selected for LCM demonstrated that two were monoclonal and six were polyclonal. We conclude that RET activation closely parallels the morphological changes, that it is restricted to those areas of the tumor with the cytological alterations and that it is detectable in both mono- and polyclonal tumors. Although the finding of microscopic foci indicative of papillary carcinoma in a hyperplastic or adenomatous nodule does not justify the interpretation of the entire lesion as papillary carcinoma, it is possible that such foci may precede the development of invasive papillary cancer.

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. © 2001 Wiley-Liss, Inc.