Recurrent loss of the FHIT gene and its impact on lymphatic metastasis in early oral squamous cell carcinoma.
CONCLUSIONS
Our findings show that copy number loss of FHIT 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).


OBJECTIVE
The purpose of this study was to identify alterations in genetic markers related to LNM in early OSCC.


METHODS
Genome-wide copy number alterations were analyzed in 14 early OSCCs with (n = 7) or without (n = 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.


RESULTS
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 (p < 0.05). Among these, loss of 3p14.2 (where the FHIT 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 (p = 0.005). Fhit immunohistochemical staining of 30 OSCCs showed that Fhit negativity was associated with cervical LNM (p = 0.032) and poor disease-specific survival (p = 0.045).
Department of Otorhinolaryngology, Head and Neck Surgery, College of Medicine, Catholic University of Korea, Seoul, Korea.
Young-Hoon
YH
Joo
Sung-Won
SW
Park
Seung-Hyun
SH
Jung
Yeon-Soo
YS
Lee
In-Chul
IC
Nam
Kwang-Jae
KJ
Cho
Jun-Ook
JO
Park
Yeun-Jun
YJ
Chung
Min-Sik
MS
Kim
D017766:Acid Anhydride Hydrolases / Q000737:chemistry / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D009333:Neck; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D012189:Retrospective Studies; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase