Background: Despite identification of the major genes and pathways involved in the development of colorectal cancer (CRC), it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that lead towards CRC. Therefore we wanted to improve our understanding of the genetic mechanisms of CRC development. Methods: We used microarrays to identify novel genes involved in the development of CRC. Real time PCR was used for mRNA expression as well as to search for chromosomal abnormalities within candidate genes. The correlation between the expression obtained by real time PCR and the presence of the KRAS mutation was investigated. Results: We detected significant previously undescribed underexpression in CRC for genes SLC26A3, TPM1 and DCN, with a suggested tumour suppressor role. We also describe the correlation between TPM1 and DCN expression and the presence of KRAS mutations in CRC. When searching for chromosomal abnormalities, we found deletion of the TPM1 gene in one case of CRC, but no deletions of DCN and SLC26A3 were found. Conclusion: Our study provides further evidence of decreased mRNA expression of three important tumour suppressor genes in cases of CRC, thus implicating them in the development of this type of cancer. Moreover, we found underexpression of the TPM1 gene in a case of CRCs without KRAS mutations, showing that TPM1 might serve as an alternative path of development of CRC. This downregulation could in some cases be mediated by deletion of the TPM1 gene. On the other hand, the correlation of DCN underexpression with the presence of KRAS mutations suggests that DCN expression is affected by the presence of activating KRAS mutations, lowering the amount of the important tumour suppressor protein decorin.

: The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed. The endpoint of the study was disease-free survival and cancer-specific survival. Overall, variant histology was identified as a significant predictor of disease-free survival (P = 0.035). The presence of any specific variant histology (squamous, glandular, micropapillary, nested, microcystic, inverted growth, villous-like, basaloid, and lymphoepithelioma-like) was identified as a significant predictor of disease-free survival (P = 0.008) and cancer-specific survival (P = 0.0001) in HGT1 bladder cancer. Therefore, our results support including micropapillary HGT1 urothelial carcinoma within the aggressive high-risk category, as suggested by some recent clinical guidelines, but also favor nested, glandular, and basaloid to be placed in the high-risk category due to their potential of aggressive, life-threatening behavior and their limited response to bacillus Calmette-Guerin therapy. Conversely, the low-risk category would include urothelial carcinomas with squamous, inverted growth, or microcystic morphology, all with limited life-threatening potential and good response to current therapy. A very low-risk category would finally include patients whose tumors present villous-like or lymphoepithelioma-like morphology. In conclusion, our findings support the value of reporting the variant histology as a feature of variable aggressiveness in HGT1 urothelial carcinoma of the bladder.

Thyroid-like follicular carcinoma of the kidney (TLFC), a rare neoplasm with low malignant potential, is histologically similar to primary thyroid follicular carcinoma, but characteristically lacks thyroid immunohistochemical markers. We report a case of 34-year old patient with nephrolithiasis. Ultrasound revealed hepatorenal cysts consistent with adult type polycystic kidney disease (ATPKD) and a cytologically confirmed left kidney tumor. Nephrectomy specimen contained sharply demarcated lesion of unusual morphology. Tubular and cystic structures lined by mostly cuboidal cells and filled with amorphous eosinophillic material, reminiscent of follicular carcinoma of the thyroid gland, were diagnostic for TLFC. Thyroid markers were negative. To our knowledge this is the first report of TFLC associated to ATPKD. Brief review of previously published TFLCs, possible relationship between entities and differential diagnosis are discussed.

Alterations of cell cycle proteins contribute to the development and biological behaviour of malignant tumours. We evaluated the distribution and prognostic significance of immunohistochemically detected proteins p53, p21, Rb, and cyclin D1 in 101 laryngeal and hypopharyngeal squamous cell carcinomas (SCC) and adjacent epithelial hyperplastic lesions (EHL). Protein expression was correlated with tumour grade and stage.Varying patterns of protein expression were found in SCC. A significant correlation (p <0.05) was found between Rb expression and tumour grade. Different grades of EHL exhibited randomly distributed p53 and cyclin D1 positive cell clusters with no association to the pattern of their expression in SCC.Our study demonstrated derailment of cell cycle regulation in almost all cases of SCC of the larynx and hypopharynx. However, only cyclin D1 expression had an independent prognostic value for cancer-specific survival. The results also suggest that Rb gene inactivation, although rare, might be more important in the development of SCC than previously thought.

Malignant salivary gland tumours are rare histologically and clinically heterogeneous group of tumours, missing prognostic factors and therapeutic targets. MicroRNAs (miRNAs), small noncoding RNAs, and posttranscriptional regulators of mRNA are poorly described in different subtypes of salivary gland tumours. Epidermal growth factor receptor (EGFR), an important therapeutic target and target of certain miRNAs (i.e.,miR-133b), shows variable degrees of expression in salivary gland tumours. Our study included 70 parotid gland tumours of different histological subtypes. Expression, mutations, and copy number variations (CNVs) of EGFR were determined using immunohistochemistry, single-stranded conformation polymorphism, quantitative polymerase chain reaction (qPCR), and fluorescence in situ hybridization. Expression ofmiR-99b,miR-133b,miR-140,miR-140-3p, andlet-7awas analysed using qPCR. Expression of EGFR was observed in 37% of tumours with low and 40% of tumours with high malignant potential. There were no mutations, with the majority of samples showing polysomy of chromosome 7. Based on histological subtypes, we found differential expression of all five miRNAs. We confirmed association of reactivity of EGFR,miR-133b,miR-140,miR-140-3p, andlet-7awith CNV of EGFR and a positive association betweenmiR-133b/let-7aand reactivity of EGFR. Age and need for postoperative radiotherapy were characterized as significant in multivariate survival analysis.