p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma

Abstract

CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a) may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC) are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a) in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3%) were positive for p16 (INK4a) and this expression was more intense in non-smoking patients (P = 0.050), whose tumors showed negative vascular embolization (P = 0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was possible to predict a probability of lower survival (P = 0.055) as well as tumors presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010). Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a) appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis.

The Prognostic Value of P16 Expression in Laryngeal Squamous Cell Carcinomas: A Large Cohort Study of Chinese Patients

“…Our data showed that the p16 positive rate in LSCC of Chinese patients was lower than the p16 positive rate in previous studies that were predominantly P16 expression has been well known as the single most important prognostic variable in OPSCC, with p16 positive OPSCC patients having better survival outcomes [13]. P16 overexpression was also proven to be associated with better prognosis of LSCC, while p16 negativity determined tumor progression and poor outcome in previous studies [26,27]. Nevertheless, the other studies on the prognostic role of p16 in laryngeal cancer present contradictory results.…”

P16 Expression Independent of Human Papilloma Virus in Egyptian Patients with Head and Neck Squamous Cell Carcinoma: A Retrospective Study

“…When underexpressed it causes uncontrolled proliferation of cancer cells, while its overexpression leads to arrest of cell division at G1-S phase thus affects the tumor size and nodal metastases i.e. the stage of tumor [33], [32], [40]. [23] could not detect a significant impact of p16 expression on T-stage of the studied 31 patients with laryngeal and hypophayngeal SCC (p 0.94).…”

“…The tumor site was not associated with p16 expression in Smith et al [32] and Ralli et al [27] trials, and in our study (p 0.4, p 0.334, and p 0.840 respectively). Silva et al [33] in their report of a cohort of laryngeal and oropharyngeal HNSCC did not show statistical difference between p16 expression and tumor localization (p16 + in 58.3% and 52.4% respectively). The carcinogenesis caused by tobacco and alcohol abuse and HPV infection is known to be synergistic to development of HNSCCs [34][35][36].…”

Expression of p16 (INK4a), cytokeratin 19, and Ki-67 in canine laryngeal squamous cell carcinoma

“…Inactivation of p16 was noted in neoplastic cell lines, which may suggest its antineoplastic effect (33). On the other hand, several authors have demonstrated high expression of the protein in malignant tumours, such as uterine carcinoma and adenocarcinoma, lymphatic leukaemia, malignant melanoma, and squamous cell carcinoma (1,39,44). Moreover, the expression was found to be correlated with the grade of tumour malignancy (1).…”