HER3 overexpression and hypomethylation in colorectal adenocarcinoma.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cancer in Malaysia. Despite advanced therapies, many cases of recurrence and resistance have been reported. Aberrant DNA methylation of HER3 has been implicated in carcinogenesis of CRC mainly through the regulation of gene expression. Hence, the objective of this study was to determine the status of HER3 DNA methylation and its effects on gene expression in CRC. MATERIALS AND METHODS: Fifty-nine of archival formalin-fixed, paraffin-embedded CRC cases with the adjacent normal colon tissues were retrieved. Manual micro-dissection was performed prior to RNA and DNA extraction. HER3 gene expression and DNA methylation status was evaluated by qPCR and methylation-specific PCR (MSP) techniques respectively. RESULTS: Upregulation of HER3 mRNA was found in CRC tissue compared to its adjacent normal colon tissue (8.04-fold). Of 59 CRC samples, 8.5% were methylated and 91.5% were unmethylated (hypomethylation). In the adjacent normal colon tissues, methylated and unmethylated tissue were observed in 6.8%and 93.2% respectively. DNA methylation of HER3 showed a significant association with tumour differentiation and tumour location. CONCLUSION: This study showed upregulation and hypomethylation of the HER3 gene in CRC cases. Epigenetic alterations were also found in the adjacent normal colon tissues. Thus, upregulation and hypomethylation of HER3 may play a key role in carcinogenesis of CRC. Hypomethylation of CpG islands might be associated with early steps during carcinogenesis. The findings of this biomarker serve a powerful approach to improve the current diagnostic and therapeutic measures.

Juxtarenal/pararenal Wilms' tumour in a six-year-old Malay girl.

We report a six-year-old Malay girl who presented with a right retroperitoneal tumour that measured 7.5 cm in diameter. A wide excision of the lesion was performed. The tumour was separated from a normal-appearing right kidney by a capsule. Microscopically, this well-encapsulated tumour was composed of classical triphasic components: epithelial, mesenchymal and blastemal areas. The immunohistochemical study showed WT1 expression in the blastemal area. Thus, a diagnosis of Wilms' tumour with favourable histology was made. The patient was well for 12 months. Extrarenal Wilms' tumour is uncommon, with the majority of cases occurring in the retroperitoneal and inguinal areas. Wilms' tumour that is not arising from the intrarenal area but shares a common capsule with the ipsilateral kidney, is even rarer. Indeed, our case would be more appropriately classified as juxtarenal/pararenal Wilms' tumour. Despite its rarity, an extrarenal or even juxtarenal/pararenal Wilms' tumour should be included in the differential diagnosis of retroperitoneal tumour.

Solid variant of papillary renal cell carcinoma.

Solid variant of papillary renal cell carcinoma is a newly recognized renal epithelial neoplasm. We encounter a case of a 36-year-old male patient with a solitary right renal tumor. The tumor is composed of solid sheets of small uniform cell with intervening micronodules, resembling the glomeruloid bodies in a metanephric adenoma. Abortive papillae rather than typical papillary formations are found in the micronodules. Furthermore, the cells in these micronodules demonstrate more cellular atypia with abundant eosinophilic cytoplasm comparing to the intervening cells. Both types of neoplastic cells are immunoreactive for epithelial membrane antigen, cytokeratins 7 and 17, but not vimentin and 34 beta E12. The features of the tumor are consistent with solid variant of papillary renal cell carcinoma. Solid variant of papillary renal cell carcinoma is similar in certain morphological and genetic features to metanephric adenoma, suggesting that they might be related.

Search for immunomodulatory effects of blood transfusion in gastric cancer patients: flow cytometry of Th1/Th2 cells in peripheral blood.

Allogeneic transfusion seems to drive the immune system toward a Th2 response and away from a Th1 response, providing a hypothetical mechanism for transfusion-induced immunomodulation. By means of an intracytoplasmic cytokine detection technique with flow cytometry, it is possible to measure Th1 and Th2 cells derived from peripheral blood mononuclear cells. This study evaluated the presence of transfusion-induced immunomodulation in 11 gastric cancer patients after gastrectomy with perioperative blood transfusion, compared to 11 gastric cancer patients who were treated by gastrectomy without transfusion. Lymphocytes subsets, including CD4 T cells, CD8 T cells, CD4/CD8 Ratio, CD2(+) T cells, CD3(+) T cells, and CD19(+) B cells, were measured in these patients, as well as variables that might suggest transfusion-induced immunomodulation, such as duration of antibiotic use, duration of hospital stay, and total hospital charges. This study also measured changes in the Th1/Th2 ratio. Th1 and Th2 lymphocytes were characterized by measuring intracellular expression of cytokines with flow cytometry. Cells were stimulated with phorbol myristate acetate and ionomycin in the presence of brefeldin-A. The results showed no significant differences in lymphocyte subsets, Th1/Th2 ratio, total hospital charges, or duration of antibiotic utilization between the groups of transfused and non-transfused gastric cancer patients after gastrectomy. The only significant difference was a longer hospital stay for transfused patients (mean 20.5 da) compared to non-transfused patients (mean 16.2 da). The anticipated finding of a Th2 response after blood transfusion was not observed. A larger group of patients may be needed to document such an effect, since many confounding variables affect the morbidity and outcome of surgery in these patients.