EZH2 (Enhancer of zeste homolog 2) promotes tumor growth and survival through numerous
mechanisms and is a promising target for novel therapeutic approaches. We aimed to
characterize the expression of EZH2 in the tumors of young head-and-neck squamous
cell cancer (HNSCC) patients in comparison with the general HNSCC patient population.
We used formalin-fixed, paraffin-embedded tissue blocks from 68 random young HNSCC
patients (≤39 years, median age: 36 years; diagnosed between 2000 and 2018), which
were compared with the samples of 58 age- and gender-matched general HNSCC subjects
(median age: 62 years; all diagnosed in the year 2014). EZH2 and p53 expression of
the tumors was detected using immunohistochemical staining. Lower EZH2 expression
was found to be characteristic of the tumors of young HNSCC patients as opposed to
the general population (median EZH2 staining intensity: 1 vs. 1.5 respectively, p
< 0.001; median fraction of EZH2 positive tumor cells: 40% vs. 60%, respectively,
p = 0.003, Mann–Whitney). Cox analysis identified a more advanced T status (T3-4 vs.
T1-2), a positive nodal status, and alcohol consumption, but neither intratumoral
EZH2 nor p53 were identified as predictors of mortality in the young patient group.
The lower EZH2 expression of young HNSCC patients’ tumors discourages speculations
of a more malignant phenotype of early-onset tumors and suggests the dominant role
of patient characteristics. Furthermore, our results might indicate the possibility
of an altered efficacy of the novel anti-EZH2 therapies in this patient subgroup.
