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Published on: April 22, 2019
p16INK4A in oral squamous cell carcinomas--a correlation with biological behaviors: immunohistochemical and FISH
Hiroyuki Suzuki1, Haruhiko Sugimura, Kenji Hashimoto
1Department of Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. hrsuzuki@hama-med.ac.jp
Purpose:
The p16(INK4A) gene and Rb gene are key tumor suppressor genes in a cell cycle regulatory pathway that is commonly inactivated in various cancers. The disruption of p16(INK4A) expression has been reported in several types of carcinoma but sparse in the area of oral oncology.
Materials And Methods:
The study included 66 cases who were diagnosed as oral squamous cell carcinoma. Immunohistochemical p16(INK4A) and pRb expression, fluorescence in situ hybridization analysis were performed to the resected materials.
Results:
p16(INK4A) protein expressions were detected in 14 cases without lymph node metastasis versus in 4 cases with metastasis (P = .04). As to histopathological grading of the effect of chemotherapy, almost all the p16(INK4A)-positive cases (9 cases out of 10) exhibited the histological feature of being rather sensitive to chemotherapy (2B and better response according to Ohboshi and Shimosato's criteria) versus 17 of 33 negative cases (P = .02). Survival curves showed that the survival rate of patients with loss of p16(INK4A) expression was significantly worse than those with amplification and normal genetic dosage of p16(INK4A) (P < .0001).
Conclusions:
The expressions of p16(INK4A) were significantly correlated with biological behavior of OSCCs. These results indicate we can use p16(INK4A) as a marker of a prognostic prediction of oral cancer and it is useful for management of OSCCs.
Insights
The p16(INK4A) gene is a crucial tumor suppressor. Its expression levels correlate with oral squamous cell carcinoma (OSCC) behavior, chemotherapy response, and patient survival, making it a valuable prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p16(INK4A) gene and Rb gene are critical tumor suppressors regulating the cell cycle.
- Their inactivation is common in various cancers, yet p16(INK4A) disruption is less studied in oral oncology.
Purpose of the Study:
- To investigate the role and prognostic significance of p16(INK4A) expression in oral squamous cell carcinoma (OSCC).
- To assess the correlation between p16(INK4A) expression and clinicopathological features, chemotherapy response, and patient survival in OSCC.
Main Methods:
- Analysis of 66 OSCC cases using immunohistochemistry for p16(INK4A) and pRb expression.
- Fluorescence in situ hybridization (FISH) was performed on resected tumor tissues.
Main Results:
- p16(INK4A) expression was significantly lower in OSCC cases with lymph node metastasis (P = .04).
- A higher proportion of p16(INK4A)-positive cases showed sensitivity to chemotherapy (P = .02).
- Loss of p16(INK4A) expression was associated with significantly worse patient survival (P < .0001).
Conclusions:
- p16(INK4A) expression is significantly correlated with the biological behavior of OSCC.
- p16(INK4A) serves as a potential prognostic marker for oral cancer.
- Evaluating p16(INK4A) expression can aid in the clinical management of OSCC.
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