Expression, Epigenetic, and Genetic Changes of HNF1B in Colorectal Lesions: an Analysis of 145 Cases.

Hepatocyte nuclear factor 1 beta (HNF1B) is transcription factor which plays a crucial role in the regulation of the development of several organs, but also seems to be implicated in the development of certain tumours, especially the subset of clear cell carcinomas of the ovary and kidney. Depending on the type of the tumour, HNF1B may act as either a tumour suppressor or an oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using immunohistochemical approach and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B on 40 cases of colorectal adenomas and 105 cases of colorectal carcinomas. The expression of HNF1B was correlated with the benign or malignant behaviour of the lesion, given that carcinomas showed significantly lower levels of expression compared to adenomas. In carcinomas, lower levels of HNF1B expression were associated with recurrence and shortened disease-free survival. The mutation analysis revealed three somatic mutations (two frameshift and one nonsense) in the carcinoma sample set. Promoter methylation was detected in three carcinomas. These results suggest that in colorectal cancer, HNF1B may play a part in the pathogenesis and act in a tumour suppressive fashion.

Stathmin is a potential therapeutic target but not a prognostic marker in melanoma: an immunohistochemical study of 323 melanocytic lesions.

In several solid tumors, an increased stathmin expression is associated with both poor prognosis and resistance to certain chemotherapy types. However, the data regarding melanocytic lesions are very limited. The goals of our study are as follows: the assessment of stathmin expression in benign and malignant melanocytic lesions, and the significance of its expression for the differential diagnostics between benign and malignant lesions; the analysis of the prognostic significance of stathmin expression in melanoma; and the evaluation of stathmin expression in melanoma and melanoma metastases with respect to possible therapeutic targeting. Immunohistochemical analysis of stathmin expression was done in 323 melanocytic lesions, including 205 primary cutaneous melanomas, 60 melanoma metastases, and 58 melanocytic nevi. Stathmin expression was found in all analyzed groups of melanocytic lesions. Using the H-scoring system, the observed intensity of expression was as follows: melanocytic nevi: 146.1 (mean) and 150 (median); melanomas: 116.7 (mean) and 110 (median); and melanoma metastases: 136.8 (mean) and 140 (median). The stathmin expression was significantly lower in the cohort of primary melanomas when compared with metastases and nevi (P=0.001). The stathmin expression showed no prognostic significance. The high stathmin expression in melanoma suggests that stathmin might be a promising marker for therapeutic targeting in ongoing clinical trials. Compared with several other solid tumors, stathmin expression in melanoma showed no prognostic significance. The potential use of stathmin expression in differential diagnostics is limited by its common expression, and despite the statistically significant differences between nevi and melanoma, it may not be used in this setting.