Cyclin D1, Retinoblastoma and p16 Protein Expression in Carcinoma of the Gallbladder

Abstract

Background: Cancer of the gallbladder is a relatively rare neoplasm with a poor prognosis. The exact mechanisms of its genesis are not known and very little information is available on molecular events leading to labeling this as an orphan cancer. Materials and Methods: In this prospective case control study we evaluated the expression of p16, pRb and cyclin D1 by immunohistochemistry to study the G1-S cell-cycle check point and its possible role in gallbladder carcinogenesis. A total of 25 patients with gallbladder carcinoma (group I), 25 with cholelithiasis (group II) and 10 normal controls. were enrolled Results: Cyclin D1 expression was seen in 10 (40%) patients each with carcinoma and cholelithiasis while only in 2 (20%) of the normal gallbladders but differences were not statistically significant (p value=0.488). p16 was expressed in 12% patients of carcinoma of the gallbladder and 28% of cholelithiasis, however this difference was not statistically significant (p value=0.095). Retinoblastoma protein was found to be expressed in 50% of normal gallbladders and 6 (24%) of carcinoma and 8 (32%) of gallstones. The present study failed to demonstrate any conclusive role of cyclin D1/RB/ p16 pathway in carcinoma of the gallbladder. Conclusions: The positive relation observed between tumor metastasis and cyclinD1 expression and p16 with nodal metastasis suggested that higher cyclin D1/p16 expression may act as a predictive biomarker for aggressive behavior of gallbladder malignancies.

Expression of epidermal growth factor receptor, p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma

“…Overexpression of cyclin D1 has been observed in 64% of patients in our study, however, previously published studies reported 5.6-41% overexpression and associated with low-grade tumors, papillary tumor morphology and predictors of survival. [2829424344] We also observed that overexpression was more in the patients with poorly differentiated tumors (84.6%), and distant metastasis (71.4%), although the result was not statically significant. This could be due to the fact that cyclin D1 influences the cell cycle by excreting its effect on cyclin dependent kinases.…”

Elevated GRP78 expression is associated with poor prognosis in patients with pancreatic cancer

“…Our tests on the cell cycle after regulating GRP78 expression reached the same conclusion, suggesting that GRP78 might affect the proliferation of PDAC cells by changing the cell cycle. Overexpression of CyclinD1 and CDK4/CDK6 was also observed in many human malignancies, including gall bladder cancer, endometrial carcinoma, and ovarian serous carcinomas 25 26 27 28 . Moreover, the apoptosis assay was also performed by FCS, but no significant difference was observed, likely because the spontaneous apoptosis of PDAC cell lines occurred at a relatively low level ( supplementary material ).…”

Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma

“…In this process, as an important member of the cyclin-dependent kinase inhibitors (CKIs), the p16 protein can competitively bind to CDK4/6, inhibit CDK4/6 activity, antagonize CCND1 function, and inhibit the progression of the cell cycle. However, the p16 gene is inactivated in most tumor tissues [5]. Our preliminary study demonstrated that the reactivation of p16 expression can induce the cell cycle arrest, promote the apoptosis of cancer cells, and inhibit the growth of tumors [6].…”