Abstract
The Wnt/β-catenin pathway plays an important role in the genesis of familial adenomatous polyposis, the most common form of inherited colorectal carcinoma (CRC). Also, the inflammatory bowel diseases (IBDs) predispose to cancer development; and cyclooxygenase 2 (COX-2) seems to be pivotal in their pathogenesis. This study aimed to investigate the relationship between the expression of COX-2 protein and β-catenin in colorectal cancer. The study enrolled 45 patients, all of whom underwent surgery and immunohistochemical staining of tissue specimens for COX-2 and β-catenin was done. Correlation between the two modulators and their relationship with clinicopathological features were examined. In 34 cases (75.56%) of the tumor samples; β-catenin immunoreactivity was found in the cytoplasm and/or membrane compartment. On the other hand, COX-2 immunoreactivity was weakly and/or strongly positive in 32 cases (71.11%) and negative in 13 (28.89%). Positivity was detected in the cytoplasm and in the perinuclear area. Increased expression of β-catenin was correlated to Duke stage (P=0.009). Furthermore, nuclear β-catenin localization showed a correlation to the Duke stage (P=0.029) and insignificant correlation with distant metastases (P = 0.336). Positive COX-2 expression showed a significant relation to, liver metastases (P = 0.042), and Duke stage (P = 0.011) and insignificant correlation to lymph node invasion (P=0.25). These data indicate that cytoplasmic/membrane β-catenin over-expressions as well as positive COX-2 expressions are associated with a more aggressive behavior of the disease.
Highlights
Colorectal cancer (CRC) is one of the most frequent malignancies and is the third most common cause of cancer-related death worldwide [1,2]
Positive cyclooxygenase 2 (COX-2) expression showed a significant relation to, liver metastases (P = 0.042), and Duke stage (P = 0.011) and insignificant correlation to lymph node invasion (P=0.25). These data indicate that cytoplasmic/membrane β-catenin over-expressions as well as positive COX-2 expressions are associated with a more aggressive behavior of the disease
The Wnt/β-catenin pathway plays a pivotal role in the genesis of familial adenomatous polyposis, the most common form of inherited CRC [1,6]
Summary
Colorectal cancer (CRC) is one of the most frequent malignancies and is the third most common cause of cancer-related death worldwide [1,2]. It might be related to a number of predisposing factors including the prior existence of benign tumours (adenomas), the prior existence of ulcerative colitis, inherited syndromes such as familial adenomatous polyposis, dietary factors such as a low fiber diet and so on [3]. The Wnt/β-catenin pathway plays a pivotal role in the genesis of familial adenomatous polyposis, the most common form of inherited CRC [1,6]. Loss-of-function mutations of the DNA repair genes coupled with genome instability are the leading causes of human non-polyposis colorectal cancer, the other inherited form of CRC [7]. Mutations of the Wnt/β-catenin pathway play a causative role in 60- 80% of sporadic cases [1,6].
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