Clinicopathological and prognostic significance of androgen receptor overexpression in colorectal cancer. Experience from Al-Madinah Al-Munawarah, Saudi Arabia.

OBJECTIVES: To examine the androgen receptor (AR) status in colorectal cancer (CRC) patients by the immunohistochemical method and to correlate the findings with all available clinicopathological parameters of prognostic significance. METHODS: Archival tumor samples were studied using immunohistochemistry for AR expression in 324 patients with CRC. Patients were diagnosed at the Pathology Department at a tertiary care Hospital, Al-Madinah Al-Munawarah, Saudi Arabia, between January 2006 and December 2017. RESULTS: There is a complete lack of AR expression in normal colonic mucosa; however, AR was expressed in 16 cases (40%) of colorectal adenoma. In CRC, AR expression was high in 118 cases (36.4%). There were no significant correlations between AR expression and gender, age, tumor histologic type, and tumor location. However, AR expression revealed a significant correlation with tumor size (p=0.026), tumor differentiation (p=0.047), American Joint Committee on Cancer (AJCC)  staging (p=0.043), lymph node positivity (p=0.018), lymphovascular invasion (p=0.018), and distant metastasis (p=0.049). In univariate Kaplan-Meier survival analysis, there was a significant (p=0.002) difference in overall survival between AR positive and negative tumors in favor of the latter. In multivariate (COX) models, high AR expression (p=0.002), AJCC (p less than 0.001), and lymphovascular invasion (p less than 0.001) were the only significant independent prognostic indicators of overall survival in CRC.Conlusion: Our study showed that the patients with higher AR expression had a significantly poorer survival rate, AR expression had the potential to be a prognostic marker of CRC.

The prognostic significance of p63 cytoplasmic expression in colorectal cancer. An immunohistochemical study.

OBJECTIVES:   To evaluate p63 expression pattern in Saudi colorectal cancer (CRC) patients and correlate that with clinicopathological parameters and its role in carcinogenesis and prognosis. METHODS: Archival tumor samples were analyzed by immunohistochemistry for p63 expression in 324 consecutive Saudi patients diagnosed with CRC between January 2006 and December 2017 at the Pathology Department of a tertiary care Hospital, Madinah, Saudi Arabia. RESULTS: P63 over-expression was absent in normal mucosa, while 12.5% cases of adenoma showed its over-expression. In CRC, p63 expression was high in 24.1% of cases. There were no significant correlations between p63 expression and gender, tumor location, tumor size and tumor histologic differentiation. However, high p63 expression revealed a significant correlation with age (p=0.035), tumor type (p=0.004), American Joint Committee on Cancer stage (p=0.046), lymph node metastasis (p=0.006), lymphovascular invasion (p=0.006), distant metastasis (p=0.049), high Ki67 expression (p=0.000) and K-ras expression (p=0.002). The Kaplan-Meier analysis revealed a shorter period of survival with p63 over-expression (p less than 0.001). The Cox-regression model analysis showed that p63 over-expression was an independent prognostic marker in CRC (p=0.000). CONCLUSION: P63 expression was increased from normal to adenoma to carcinoma sequence. Moreover, p63 cytoplasmic expression seems to be related to high Ki67 indexing, K-ras expression, advanced tumor stage and poor clinical outcome of CRC. These findings suggest a significant role of cytoplasmic p63 expression in tumor progression and prognosis.

Impact of cyclooxygenase-2 over-expression on the prognosis of colorectal cancer patients. An experience from Western Saudi Arabia.

OBJECTIVES: To evaluate cyclooxygenase-2 (COX-2) over-expression in colorectal cancer (CRC) and its role in carcinogenesis and prognosis. METHODS: It was a retrospective study. Archival samples were obtained from Pathology Department at King Fahad Hospital, Madinah, Saudi Arabia, over 11 years' period (January 2006 to December 2017). Samples were analyzed using immunohistochemistry for COX-2 and Ki67 over-expression in 324 CRC patients, 40 cases of colorectal adenomas and 20 cases of normal colonic mucosa. RESULTS: Cyclooxygenase-2 over-expression was observed in 40% of normal colonic mucosa, 65% of colorectal adenoma and 84.6% of CRC cases. There were no significant correlations between COX-2 over-expression and age, gender, tumor site, or tumor size. However, COX-2 over-expression revealed highly significant correlations with tumor differentiation, lymph node metastasis, lympho-vascular invasion, distant metastasis, advanced stages, and high Ki67 expression. Univariate Kaplan-Meir survival analysis showed that patients with high COX-2 expression had significantly shorter periods of survival. Multivariate analysis by means of the COX-2 regression model revealed that high COX-2 over-expression, AJCC, and Ki67 expression were the only significant independent prognostic indicators. CONCLUSION: Cyclooxygenase-2 over-expression increases during normal-adenoma-carcinoma sequence, moreover COX-2 over-expression is associated with advanced tumor stage and Ki67 over-expression. These findings suggest a significant role of COX-2 in the carcinogenesis and prognosis of CRC in our study population.