SMAD4 and metastatic malignant neoplasm in the lymph nodes: Multivariate analysis showed that lymph node metastasis (relative risk (RR): 2.222, P = 0.014), negative Smad4 IHC labeling (RR: 0.269, P < 0.001) and negative P16 IHC labeling (RR: 0.360, P < 0.001) were independent predictors of OS (Table 3).