Simple SummaryWe are going to highlight new prognostic and predictive factors, CD44, PDL1, and ATG7, in surgical samples from patients with laryngeal squamous cell carcinoma (LSCC). Immunohistochemical analysis with primary antibodies anti-CD44, PD-L1 and ATG7 was performed using the tissue microarray (TMA) technique. Considering follow-up data, the 5-year disease-free survival (DFS) was 85.71% and 36% for CD44-negative and -positive tumors. The 5-year DFS was 60% and 33.33% for negative and positive PDL1 tumors, respectively. At the follow-up, 5-year DFS was 58.06% and 37.50% for negative and positive ATG7 tumors.AbstractWe focus on the new prognostic and predictive factors CD44, PDL1, and ATG7 in our study of surgical samples of patients with laryngeal squamous cell carcinoma (LSCC) using tissue microarray (TMA). Thirty-nine previously untreated patients affected by laryngeal carcinoma who then underwent surgical treatment were considered in this retrospective study. All surgical specimens were sampled, embedded in paraffin blocks, and stained with hematoxylin and eosin. A representative sample of the tumor was chosen and transferred into a new block of paraffin, the recipient block, to perform immunohistochemical analysis with the primary antibodies anti-CD44, PD-L1, and ATG7. At follow-up, 5-year disease-free survival (DFS) for negative and positive tumors was determined as 85.71% and 36% for CD44, 60% and 33.33% for PDL1, and 58.06% and 37.50% for ATG7, respectively. Multivariate analysis revealed that CD44 expression is an independent predictive factor of low-grade tumors (p= 0.008), lymph node metastasis at the time of diagnosis, and AGT7 negativity. Thus, CD44 expression is a potential marker for more aggressive forms of laryngeal cancer.