P38 expression in colorectal adenomas: relationships to cell proliferation, stem phenotype and AKT pathway proteins.

BACKGROUND: The P38-protein is known to be expressed in colorectal adenomas (CRA). Expression in low- and high-grade tubular adenomas is decreased when compared to adenocarcinomas and increased with regard to normal mucosa. We aimed to study P38 expression in human CRAs and the relationships to cell proliferation Ki67-protein, stem-phenotype CD133-protein and, to mTOR-protein (AKT pathway). METHODS: The immunohistochemical expression of P38 was evaluated in CRAs on tissue microarrays. Data were analyzed with the Kendall-rank-correlation test. RESULTS: Nuclear P38 correlated to low-grade dysplasia (Kendall P<0.01/tau=-0.254) and to decreased adenoma size (P<0.01/tau=-0.267). Nuclear P38 also correlated to cytoplasmic or membrane mTOR (P<0.01/tau=-0.223 and P<0.01/tau=-0.340) and to cytoplasmic CD133 (P<0.01/0.293). An inverse relationship was observed to Ki67 (P<0.00/ tau=-0.110). CONCLUSIONS: Our results suggest an interference of P38 with initial steps of colorectal adenomagenesis. The correlation to mTOR suggests a biological crosstalk between the MAPK- and AKT-signaling-pathways in colorectal adenomagenesis at P38 level.

Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation.

Thyroid heterotopic bone formation (HBF) in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33-82 years). The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.). Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.). The number and size of HBFs (total: 28) ranged between 1 and 23/thyroid gland (one bilateral) and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular). The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp.) without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm), and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated.

PTEN expression in colorectal adenomas: relationship to morphology and cell heterogeneity.

INTRODUCTION: Colorectal adenomas are the most frequent benign colorectal tumors. These tumors are characterized by dysplasia, low and high grade, the latter having the potential to evolve to adenocarcinoma. The aim of this study was to study the expression patterns of PTEN protein in a series of colorectal adenomas and the relationships to cell proliferation and CD133, marker of stem phenotype. METHODS: Colorectal adenomas were studied for the immunohistochemical expression of PTEN on tissue microarrays. PTEN expression was analysed with regard to morphological features and with regard to the Ki67 and CD133-positive cell compartments by using the Kendall rank-correlation test. RESULTS: PTEN was expressed in 92% adenomas, either in a cytoplasmic or nuclear pattern. Cytoplasmic PTEN was correlated to cytoplasmic CD133 (p = 0.02, tau 0.191) while nuclear PTEN to decreased adenoma size and to tubular architecture (p = 0.01, τ-0.184 and p = 0.01, τ-0.183). Nuclear PTEN was also correlated to low grade intraepithelial neoplasia, while global PTEN (nuclear or cytoplasmic) was correlated to the presence of a decreased Ki67-positive component but with marginal significance (p = 0.06, τ-0.144 and p = 0.07, τ-0.213). CONCLUSION: The results of this study suggest a role for PTEN in colorectal adenoma morphogenesis and cell protein heterogeneity, being correlated to decreased size, tubular architecture and a high CD133-positive component.