Selective expression of KCNA5 and KCNB1 genes in gastric and colorectal carcinoma.

BACKGROUND: Gastric and colorectal cancers are the most common malignant tumours, leading to a significant number of cancer-related deaths worldwide. Recently, increasing evidence has demonstrated that cancer cells exhibit a differential expression of potassium channels and this can contribute to cancer progression. However, their expression and localisation at the somatic level remains uncertain. In this study, we have investigated the expression levels of KCNB1 and KCNA5 genes encoding ubiquitous Kv2.1 and Kv1.5 potassium channels in gastric and colorectal tumours. METHODS: Gastric and colorectal tumoral and peritumoral tissues were collected to evaluate the expression of KCNB1 and KCNA5 mRNA by quantitative PCR. Moreover, the immunohistochemical staining profile of Kv2.1 and Kv1.5 was assessed on 40 Formalin-Fixed and Paraffin-Embedded (FFPE) gastric carcinoma tissues. Differences in gene expression between tumoral and peritumoral tissues were compared statistically with the Mann-Whitney U test. The association between the clinicopathological features of the GC patients and the expression of both Kv proteins was investigated with χ2 and Fisher's exact tests. RESULTS: The mRNA fold expression of KCNB1 and KCNA5 genes showed a lower mean in the tumoral tissues (0.06 ± 0.17, 0.006 ± 0.009) compared to peritumoral tissues (0.08 ± 0.16, 0.16 ± 0.48, respectively) without reaching the significance rate (p = 0.861, p = 0.152, respectively). Interestingly, Kv2.1 and Kv1.5 immunostaining was detectable and characterised by a large distribution in peritumoral and tumoral epithelial cells. More interestingly, inflammatory cells were also stained. Surprisingly, Kv2.1 and Kv1.5 staining was undoubtedly and predominantly detected in the cytoplasm compartment of tumour cells. Indeed, the expression of Kv2.1 in tumour cells revealed a significant association with the early gastric cancer clinical stage (p = 0.026). CONCLUSION: The data highlight, for the first time, the potential role of Kv1.5 and Kv2.1 in gastrointestinal-related cancers and suggests they may be promising prognostic markers for these tumours.

Expression of epidermal growth factor receptor (EGFR) in colorectal cancer: An immunohistochemical study.

BACKGROUND AND STUDY AIM: The epidermal growth factor receptor (EGFR) plays an important role in tumourigenesis and tumour progression of colorectal cancer (CRC) and leads to the activation of intracellular signaling pathways. The use of anti-EGFR-targeted therapy has increased for patients with metastatic CRC. Today, the clinical utility of immunohistochemistry has remained somewhat inconclusive. It is based on EGFR screening methods using paraffin-embedded tumour specimen to select patients eligible for treatment. There is still lack of agreement on reproducible scoring criteria for EGFR immunohistochemistry has in various clinical trials. PATIENTS AND METHODS: We retrospectively reviewed 36 CRC patients who underwent surgeries during 2011 in Habib Thameur hospital in Tunis. We analyzed the immunohistochemical overexpression of EGFR using a score based on immunostaining intensity. In addition, we analyzed the correlation between this overexpression and patients' clinicopathologic parameters. RESULTS: The positive expression rate of EGFR was 78% (28/36). Using the immunoreactivity score, 21 cases were considered low grade expression and 15 tumours were high grade. Immunohistochemical expression of EGFR showed a significant difference with tumour's location (p = 0.034) and vascular invasion (p = 0.03). This expression was not significantly associated with age, gender, tumour size, histological type, grade, TNM staging and perineural invasion. CONCLUSIONS: EGFR expression by immunohistochemistry in CRC is variably correlated with clinicopathological parameters. Its assessment by this method has still not proved its predictive value.