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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Clinical significance of molecular alterations in histologically negative surgical margins of head and neck cancer patients

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Author(s):
de Carvalho, Ana Carolina [1] ; Kowalski, Luiz Paulo [2] ; Froes Marques Campos, Antonio Hugo Jose [3] ; Soares, Fernando Augusto [3] ; Carvalho, Andre Lopes [4] ; Vettore, Andre Luiz [1]
Total Authors: 6
Affiliation:
[1] Univ Fed Sao Paulo, Lab Mol Canc Biol, Dept Biol Sci, BR-04039032 Sao Paulo - Brazil
[2] Hosp Canc AC Camargo, Fundacao Antonio Prudente, Dept Head & Neck Surg, BR-01509010 Sao Paulo - Brazil
[3] Hosp Canc AC Camargo, Fundacao Antonio Prudente, Dept Pathol, BR-01509010 Sao Paulo - Brazil
[4] Hosp Canc Barretos, Dept Head & Neck Surg, Fundacao PIO 12, BR-14784400 Barretos, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Oral Oncology; v. 48, n. 3, p. 240-248, MAR 2012.
Web of Science Citations: 30
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. (C) 2011 Elsevier Ltd. All rights reserved. (AU)