angiogenin and Laryngeal-Neoplasms

Combining primary surgery with postoperative radiotherapy (RT) significantly reduces locoregional recurrence rates in selected patients with laryngeal squamous cell carcinoma (SCC). A prognostic model was used to see if associating laryngeal SCC tissue markers (mammary serine protease inhibitor [MASPIN], CD105, angiogenin [ANG], and nm23-H1) with conventional criteria could better discriminate higher-risk patients warranting postoperative RT.. The study involved 76 consecutively operated patients with laryngeal SCC not recommended for postoperative RT, in accord with current guidelines.. On multivariate statistical modeling, non-nuclear MASPIN expression (p = .022), a CD105 expression ≥ 5.28% in vascular endothelial cells (p = .003), an nm23-H1 nuclear expression in carcinoma cells ≤ 12.0% (p = .028), and an ANG expression ≥ 5.0% (p = .07, statistical trend) showed a negative prognostic significance. The discriminatory power for disease recurrence of the 4 considered biomarkers generated an area under the curve (AUC; receiver operating characteristic [ROC]) of 0.872. The Hosmer-Lemeshow scale indicated an excellent discriminatory power.. This panel's ability to predict laryngeal SCC recurrence warrants further prospective, randomized studies to assess its use among the parameters routinely considered before recommending postoperative RT for patients with laryngeal SCC.

Topics: Aged; Analysis of Variance; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cohort Studies; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Laryngeal Neoplasms; Laryngectomy; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; NM23 Nucleoside Diphosphate Kinases; Pilot Projects; Predictive Value of Tests; Prognosis; Radiotherapy, Adjuvant; Ribonuclease, Pancreatic; ROC Curve; Sensitivity and Specificity; Serpins; Squamous Cell Carcinoma of Head and Neck; Survival Analysis

Patients with head and neck squamous cell carcinoma (SCC) respond very differently to radiotherapy (RT). Since clinical factors cannot accurately predict its effects, biological parameters have been investigated, including tumor hypoxia. CD105 is a hypoxia-inducible glycoprotein emerging as a potential prognostic indicator for several solid malignancies. Angiogenin is upregulated under hypoxic conditions and supports primary and metastatic tumor growth. Epidermal growth factor receptor (EGFR) activation stimulates tumor proliferation and angiogenesis. The aim of the present study was to ascertain the prognostic importance of hypoxia-inducible factors (CD105, angiogenin) and EGFR in a series of patients who underwent primary surgery followed by RT for laryngeal SCC. 25 consecutive patients with laryngeal SCC given postoperative RT have been investigated. CD105, angiogenin, and EGFR immunohistochemical expressions in primary laryngeal SCCs have been evaluated also with image analysis. The recurrence rate was significantly higher in SCC patients with a CD105 expression >10.0% (P = 0.012) and their disease-free survival (DFS) was shorter (P = 0.044). Neither angiogenin (in the carcinoma cells or endothelial cells) nor EGFR expression were associated with the prognosis in our patients after primary surgery followed by RT for laryngeal SCC. CD105 should be studied as a potentially predictive biomarker for identifying laryngeal SCCs at higher risk of early recurrence after postoperative RT. Targeted anti-CD105 therapy associated with RT should also be investigated in patients with laryngeal SCCs characterized by high CD105 expression.

Topics: Aged; Antigens, CD; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Endoglin; ErbB Receptors; Female; Follow-Up Studies; Humans; Immunohistochemistry; Italy; Laryngeal Neoplasms; Laryngectomy; Male; Neoplasm Staging; Postoperative Period; Prognosis; Receptors, Cell Surface; Retrospective Studies; Ribonuclease, Pancreatic; Survival Rate

  Angiogenin regulates angiogenesis supporting primary and metastatic tumour growth. CD105 is a proliferation-associated protein expressed in angiogenic endothelial cells. The aim of this study was to investigate for the first time angiogenin expression in laryngeal squamous cell carcinoma (LSCC) and to evaluate the relationship between angiogenin and CD105 expression, clinicopathological and prognostic parameters..   A total of 108 consecutive operable LSCCs were studied. Angiogenin expression was determined immunohistochemically in both carcinoma cells and intratumoral vessels. CD105 expression was evaluated in endothelial cells of LSCC and calculated by a computer-based image analysis system. The percentage of the fields occupied by CD105-assessed microvessels was determined. Angiogenin expression in carcinoma cells was higher in LSCC patients who experienced loco-regional recurrence of disease (P=0.032). Disease-free survival (DFS) was shorter in cases with carcinoma cells showing angiogenin expression >21.0% (P=0.035). Angiogenin expression in carcinoma cells was correlated strongly with the angiogenin score in endothelial cells of intratumoral vessels (P=0.0000). Higher loco-regional carcinoma recurrence rate and shorter DFS in patients with high CD105 expression were found (P=0.0004, P=0.0001)..   Angiogenin expression in laryngeal carcinoma cells and CD105 expression can be considered as potentially useful to detect LSCC patients with higher risk of disease recurrence who might benefit from more aggressive therapy.

Topics: Aged; Antigens, CD; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Endoglin; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Kaplan-Meier Estimate; Laryngeal Neoplasms; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Neovascularization, Pathologic; Receptors, Cell Surface; Ribonuclease, Pancreatic