Related Experiment Video
Updated: Aug 19, 2026

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Cell cycle-related gene abnormalities and product expression in esophageal carcinoma
M Roncalli1, S Bosari, A Marchetti
1Department of Pathology, Humanitas Clinical Institute, University, University of Milan School of Medicine, Rozzano, Italy.
Abstract:
In esophageal carcinoma, individual genetic alterations of cyclins, cyclin-dependent kinase inhibitors, and final effectors of the G1-to-S transition have been documented. Our aim was to design a comprehensive analysis of the role and clinical significance of some critical genes, namely cyclin D1, MTS1, and Rb. To this end, cyclin D1 gene amplification and protein accumulation, Rb gene allelic loss and protein expression, and MTS1 gene mutation and DNA methylation were investigated in a series of 74 esophageal carcinomas. Cyclin D1 amplification was documented in 17 of 55 (31 %) cases, being a feature of squamous cell type (14 of 17 amplified cases). Cyclin D1 accumulation significantly correlated with lymph node metastasis (p < 0.02), advanced tumor stage (p < 0.05), and a reduced overall survival rate (p < 0.03). Rb gene loss of heterozygosity occurred in 14 of 39 (36%) informative cases and was associated with an unfavorable survival rate (p < 0.01). MTS1 gene mutations were detected in 2 adenocarcinomas only; gene methylation was observed in 17 of 72 cases (24%) without any correlations with the variables investigated. A direct association between cyclin D1 and Rb gene accumulation (p < 0.0005) and an inverse one between RB loss of heterozygosity and MTS1 abnormalities (p < 0.05) emerged from this study. These results have important clinical implications because both cyclin D1 and Rb gene deregulation are significantly related to an unfavorable survival rate. In addition, cyclin D1 amplification is associated with esophageal carcinoma of squamous cell type, being totally absent in adenocarcinomas (p < 0.01). The combined evaluation of these genes also demonstrates that molecular abnormalities of genes belonging to the same pathway are mutually exclusive and unnecessary for the neoplastic transformation and tumor progression.
Insights
Genetic alterations in cyclin D1 and Rb genes are linked to poor survival in esophageal carcinoma. Cyclin D1 amplification specifically indicates squamous cell type, highlighting their clinical significance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Esophageal carcinoma exhibits genetic alterations in cell cycle regulators.
- Previous studies identified individual genetic changes in G1-to-S transition genes.
Purpose of the Study:
- To comprehensively analyze the role and clinical significance of cyclin D1, MTS1, and Rb genes in esophageal carcinoma.
- To investigate gene amplification, protein accumulation, allelic loss, mutation, and methylation of these critical genes.
Main Methods:
- Analysis of cyclin D1 gene amplification and protein accumulation.
- Investigation of Rb gene allelic loss and protein expression.
- Assessment of MTS1 gene mutation and DNA methylation in 74 esophageal carcinomas.
Main Results:
- Cyclin D1 amplification (31%) was associated with squamous cell carcinoma and poor survival.
- Rb gene loss of heterozygosity (36%) correlated with unfavorable survival.
- MTS1 mutations were rare; methylation (24%) showed no significant correlations.
- Direct association between cyclin D1 and Rb accumulation; inverse association between Rb loss and MTS1 abnormalities.
Conclusions:
- Deregulation of cyclin D1 and Rb genes significantly predicts poor survival in esophageal carcinoma.
- Cyclin D1 amplification is a marker for squamous cell type, absent in adenocarcinomas.
- Molecular abnormalities within the same pathway appear mutually exclusive in neoplastic progression.
Related Concept Videos
Mitogens and the Cell Cycle
Abnormal Proliferation
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Abnormal Proliferation

