SMAD4 and pachyonychia congenita: Moreover, even if the ratios of SMAD4 loss may be similar in each single study, the majority of studies claiming SMAD4 loss as a strong negative prognostic biomarker were carried out in resected PC of primarily Asian populations [10,15,16,17], whereas some equally large studies in European, American or Australian populations did not detect this association [9,12,19,20].