Prognostic impact of intra-field heterogeneity in oral squamous cell carcinoma
VIRCHOWS ARCHIV
Authors: Gabusi, Andrea; Gissi, Davide Bartolomeo; Montebugnoli, Lucio; Asioli, Sofia; Tarsitano, Achille; Marchetti, Claudio; Balbi, Tiziana; Helliwell, Timothy R.; Foschini, Maria P.; Morandi, Luca
Abstract
Genetic heterogeneity displayed by tumour cells (intratumoural heterogeneity, ITH) represents a diagnostic challenge when assessing tumour mutational profile. In oral squamous cell carcinoma (OSCC), ITH may be found both in tumour cells and in adjacent mucosa. Genetic heterogeneity of the adjacent mucosa can be interpreted as evidence of the field cancerization (field heterogeneity, FH). The aim of the study was to investigate the impact of intratumoural and intrafield heterogeneity on locoregional control. Ten OSCC patients (5 recurrent and 5 nonrecurrent) were studied. Multiple areas were sampled from the bulk of the tumour and the adjacent nonneoplastic mucosa. A panel of 10 tumour-specific OSCC driver genes was analysed for each sample and was used to calculate heterogeneity. Values were compared among recurrent and nonrecurrent OSCC. Mutational analysis highlighted that a single tumour sample has limited accuracy in assessing the genetic profiles of tumours. High values of ITH considering shared mutations between specimens were found in both recurrent and non-recurrent OSCC (p = 0.095). On the contrary, the intrafield genetic heterogeneity was significantly less frequently in the non-recurrent OSCC group (p = 0.032). Heterogeneity within each specimen calculated with variant allele frequency confirmed that there was better discrimination between recurrent and nonrecurrent groups using nonneoplastic adjacent mucosa than tumour tissue (p value 0.0006 and 0.0048 respectively). In agreement with the theory of field cancerization, intrafield genetic heterogeneity correlates with a higher risk of developing loco-regional recurrences and second primaries. In order to reduce the ITH effects, analysis of multiple tumour areas should be encouraged.
Quantitative Characterization of Bone Viability of Femoral Head and Subchondral Bone by Using Single Photon Emission Computerized Tomography/Computerized Tomography (SPECT/CT)
MEDICAL SCIENCE MONITOR
Authors: Cao, Lu; Liao, Yanan; Song, Chunfeng; Jiang, Haochen; Chen, Zenggan; Yan, Zuoqin; Guo, Changan
Abstract
Background: Vascularized fibular grafting (VFG) has been successfully employed for treating avascular necrosis of the fem-oral head (ANFH). In this study, we aimed to evaluate the bone viability of the femoral head and subchondral bone following VFG by using single photon emission computerized tomography and computerized tomography (SPECT/CT). Material/Methods: Between March 2011 and June 2014, 14 ANFH patients (17 hips) treated with VFG at Zhongshan Hospital, Fudan University, were prospectively enrolled. The patients included 9 males and 5 females with an average age of 26.6 years (range, 18-34 years). According to the ARCO (Association Research Circulation Osseous) stage criteria, 3 hips corresponded to stage IIA, 4 hips to stage IIB, 2 hips to stage IIC, 5 hips to stage IIIA, and 3 hips to stage IIIB. A novel method based on SPECT/CT was developed to quantitative characterized the bone viability of femoral head and subchondral bone prior to surgery and at 3 months after VFG. All patients were followed for an average duration of 3.8 years (ranging 2.6-5.5 years). Results: The bone viability of the femoral head (V-fh) and subchondral bone (V-sb) of patients' hips at ARCO stage III was 58.9 +/- 7.6 and 48.9 +/- 6.1, respectively, which were significantly lower than the preoperative V-fh (78.1 +/- 5.2) and V-sb (69.8 +/- 4.3) of hips at stage II (P<0.05). The V-fh of hips at stage II improved to 104.0 +/- 9.7 at 3 months post-intervention, and there was no significant difference compared with the V-fh (97.3 +/- 7.4) of hips at stage III (P=0.15). The V-sb of hips at stage III improved to 80.4 +/- 7.3 at 3 months after VFG; however, this value was significantly lower than that of hips at stage II (92.7 +/- 5.5) (P<0.05). Conclusions: The V-fh and V(sb )of our patients were associated with their ARCO stages, and could be improved after vascularized fibular grafting procedure as measured by SPECT/CT.