Prognostic impact of intra-field heterogeneity in oral squamous cell carcinoma
Prognostic impact of intra-field heterogeneity in oral squamous cell carcinoma
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DOI：
10.1007/s00428-019-02656-z
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发表时间：
2020-04-01
期刊：
影响因子：
3.5
通讯作者：
Morandi, Luca
中科院分区：
文献类型：
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作者：
Gabusi, Andrea;Gissi, Davide Bartolomeo;Morandi, Luca
肿瘤细胞显示的遗传异质性（肿瘤内异质性，ITH）是评估肿瘤突变谱时的诊断挑战。在口腔鳞状细胞癌（OSCC）中，ITH可以在肿瘤细胞和邻近粘膜中发现。邻近粘膜的遗传异质性可被解释为野区癌变的证据（野区异质性，FH）。该研究的目的是研究肿瘤内和场内异质性对局部区域控制的影响。我们研究了10例OSCC患者（5例复发，5例非复发）。从肿瘤的主体和邻近的非肿瘤性粘膜上取样多个区域。对每个样本的10个肿瘤特异性OSCC驱动基因进行分析，并用于计算异质性。比较复发性和非复发性OSCC的数值。突变分析强调，单个肿瘤样本在评估肿瘤遗传谱方面的准确性有限。在复发性和非复发性OSCC中，考虑到标本之间共有的突变，ITH值都很高（p = 0.095）。相反，非复发性OSCC组的场内遗传异质性显著降低（p = 0.032）。通过变异等位基因频率计算每个标本内的异质性，证实使用非肿瘤邻近粘膜比肿瘤组织更好地区分复发组和非复发组（p值分别为0.0006和0.0048）。与野区癌变理论一致，野区内遗传异质性与发生局部区域复发和第二次原发的高风险相关。为了减少ITH的影响，应鼓励对多个肿瘤区域进行分析。
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.