Recurrent loss of the <i>FHIT</i> gene and its impact on lymphatic metastasis in early oral squamous cell carcinoma

다국어 초록 (Multilingual Abstract)

<P><I>Conclusion:</I> Our findings show that copy number loss of <I>FHIT</I> is associated with lymph node metastasis (LNM) and suggest that the down-regulation of Fhit indicates poor prognosis in early oral squamous cell carcinoma (OSCC). <I>Objectives:</I> The purpose of this study was to identify alterations in genetic markers related to LNM in early OSCC. <I>Methods:</I> Genome-wide copy number alterations were analyzed in 14 early OSCCs with (<I>n</I> = 7) or without (<I>n</I> = 7) cervical LNM using 180K array-comparative genomic hybridization. To explore the prognostic implications of the most significantly associated genetic alteration with cervical LNM, immunohistochemical analysis was conducted in 30 OSCCs. <I>Results:</I> A total of 11 recurrently altered regions (RARs) were identified in the 14 OSCC cases. Six RARs on chromosomes 3p26-3p14, 5q22, and 9p21 were found to be significantly more common in early OSCC with LNM (<I>p</I> < 0.05). Among these, loss of 3p14.2 (where the <I>FHIT</I> gene is located) was the most frequent (five of seven patients with LNM, and none of seven without LNM), and most significantly associated with cervical LNM (<I>p</I> = 0.005). Fhit immunohistochemical staining of 30 OSCCs showed that Fhit negativity was associated with cervical LNM (<I>p</I> = 0.032) and poor disease-specific survival (<I>p</I> = 0.045).</P>