title: Clinical significance of molecular alterations in histologically negative surgical margins of head and neck cancer patients.
abstract: The development of locoregional recurrence is the main reason for treatment failure in head and neck squamous cell carcinomas (HNSCC) and the remaining of tumor cells in surgical margins is associated with recurrence. Surgical margins are considered negative based on histologic assessment of the pathological specimen. However, this method lacks sensitivity in identifying cells that already started malignant transformation but have not yet developed a pathologic phenotype. We investigated the usefulness of assessing the expression of PTHLH, EPCAM, MMP9, LGALS1 and MET for the detection of molecular alterations in histologically negative surgical margins and determine the correlation of these tumor-related alterations with clinical and prognostic parameters. Differential gene expression was determined by quantitative RT-PCR analyses in normal mucosa, HNSCC and negative margin samples. Thirty-eight percent of the histologically negative surgical margins examined were margin-positive for overexpression of at least one of the genes evaluated. Moreover, MMP9 and PTHLH overexpression in the surgical margins was associated with the development of second primary tumors (p=0.002) and lower rates of local control (log rank test p=0.022; HR=4.186; p=0.035), respectively. These findings demonstrate that the overexpression of tumor-related genes in histologically negative surgical margins is a frequent event. The use of qRT-PCR may be an useful tool in detecting actually negative HNSCC surgical margins and the overexpression of specific genes in these margins could be helpful in the identification of patients with a higher risk of developing second primary tumors and local recurrences, thus aiding the surgeon in the delineation of the HNSCC resection extent and helping in the planning of adjuvant therapy.
authors: Laboratory for Molecular Cancer Biology, Department of Biological Sciences, Federal University of São Paulo, Rua Pedro de Toledo, 669, 11° andar, São Paulo, SP 04039-032, Brazil.
authors: Ana Carolina
authors: AC
authors: de Carvalho
authors: Luiz Paulo
authors: LP
authors: Kowalski
authors: Antônio Hugo José Fróes Marques
authors: AH
authors: Campos
authors: Fernando Augusto
authors: FA
authors: Soares
authors: André Lopes
authors: AL
authors: Carvalho
authors: André Luiz
authors: AL
authors: Vettore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D005500:Follow-Up Studies; D037483:Galectin 1 / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018365:Neoplasm, Residual / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D037483:Galectin 1; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020780:Matrix Metalloproteinase 9