The Expression of Stem Cell Marker LGR5 and Its Coexpression with Β-Catenin in Sporadic Colorectal Carcinoma and Adenoma: A Comparative Immunohistochemical Study.

Background: LGR5 is one of the most important stem cell markers for colorectal cancer (CRC), as it potentiates Wnt/Β-catenin signaling. The well-characterized deregulation of Wnt/Β-catenin signaling that occurs during adenoma/carcinoma sequence in CRC renders LGR5 a hopeful therapeutic target. We assessed the immunohistochemical expression of LGR5 and Β-catenin in normal colonic and tumorous lesions with a clinicopathological correlation. Methods: Tissue blocks and clinical data of 50 selected cases were included: 8 from normal mucosa, 12 cases of adenoma, and 30 cases of CRC, where sections were cut and re-examined and the immunohistochemical technique was conducted using anti-LGR5 and anti-Β-catenin to measure the staining density. Results: There was no expression of LGR5 in normal mucosa compared to samples of adenoma and CRC samples. The association analysis showed that CRC specimens were more likely to have strong LGR5 and Β-catenin expressions than the other two groups (p = 0.048 and p < 0.001, respectively). Specimens with high-grade dysplastic adenoma were more likely to express moderate-to-strong expression of LGR5 and Β-catenin (p = 0.013 and p = 0.036, respectively). In contrast, there were no statistically significant associations between LGR5 and Β-catenin expression with grade and stage. Conclusion: These results suggest and support the possible role of LGR5 as a potential marker of cancer stem cells in sporadic colorectal carcinogenesis in addition to a prognostic value for LGR5 and Β-catenin in adenomatous lesions according to immunohistochemical expression density. A potential therapeutic role of LGR5 in CRC is suggested for future studies based on its role in pathogenesis.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

INTRODUCTION: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. METHODS: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. RESULTS AND CONCLUSION: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.