Altered expressions of Notch-1 signaling proteins and beta-catenin in progression of carcinoma in situ into squamous carcinoma of uterine cervix

Abstract

Background: Activation of Notch-1 signaling pathway and loss of membranous beta-catenin have been known to play key roles in the progression of uterine cervix cancer and thus this study focused any alteration in the expression patterns for Notch-1, p53, and cyclin D1 as well as beta-catenin in squamous carcinoma in situ (CIS) and invasive squamous carcinomas to investigate their roles in the progression of CIS to squamous carcinomas. Materials and Methods: Three Notch-1 signaling proteins, such as Notch-1, TP53, and cyclin D1, and a component of cell adhesion complex, beta-catenin, were immunohistochemically stained in 112 uterine cervical tumors including 74 CIS and 38 invasive squamous carcinomas (11 microinvasive and 27 invasive carcinomas). Each immunohistochemical result was compared between CIS and squamous carcinoma groups and the difference was statistically analyzed. Results: Notch-1 protein expression was significantly higher in the microinvasive and invasive carcinomas than in CIS lesions (P = 0.001). Cyclin D1 and p53 immunoreactivities tended to be expressed higher in the invasive group than in CIS (P = 0.056 and 0.060). Membranous beta-catenin expression was significantly reduced in squamous carcinomas compared to CIS (P = 0.000). However, both CIS and squamous carcinoma groups revealed no interrelationship among Notch-1 signaling proteins and beta-catenin. Conclusion: Altered expressions of Notch-1 signaling proteins and beta-catenin in the progression of CIS into squamous carcinoma of uterine cervix suggests that Notch-1 signaling pathway and cell adhesiveness might play key roles in the stromal invasion of CIS cells.

Keywords

• Beta-catenin
• carcinoma in situ
• cyclin D1
• Notch-1 protein
• squamous carcinoma
• TP53 protein
• uterine cervix