Loss of Fhit Expression in Head and Neck Squamous Cell Carcinoma and Its Potential Clinical Implication

Tai, Shyh Kuan; Lee, Janet I.; Ang, K. Kian; El‐Naggar, Adel K.; Hassan, Khaled A.; Liu, Diane; Lee, J. Jack; Ren, Hening; Hong, Waun Ki; Li, Mao

doi:10.1158/1078-0432.ccr-04-0208

Cited by 21 publications

(23 citation statements)

References 21 publications

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“…A tumor suppressor role for FHIT was postulated based on the ability of FHIT to eliminate or reduce the tumorigenicity of tumor cells in nude and knockout mice (34,35) and is now widely accepted (6). Several reports showed previously that loss of heterozygosity occurs frequently at the chromosome region containing FHIT (4,5,36) and that the expression of FHIT is frequently altered in head and neck SCC (11,19,21,37,38) and POLs (6,22,39).…”

Section: Discussionmentioning

confidence: 99%

Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Kujan

Oliver

Roz

et al. 2006

Clinical Cancer Research

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Pupose: Fragile histidine triad (FHIT) expression in precursor oral lesions (POL) and oral squamous cell carcinomas (OSCC) was studied with regard to (a) the frequency of loss of FHIT expression, (b) whether loss of FHITexpression correlates with degree of dysplasia in POLs, (c) whether FHIT loss predicts high-risk POLs that are more likely to transform, and (d) whether FHIT loss in OSCCs correlates with survival. Experimental Design: Ninety-four POLs and 86 OSCCs were immunostained for FHIT. Survival analysis was done for cases with validated clinical outcomes. Results: By optimizing the immunostaining protocol, we found that FHIT is expressed in a distinctive strong nuclear and weak cytoplasmic pattern in oral tissues. Loss of FHIT expression was found in 42 of 94 (45%) POLs and in 66 of 86 (77%) OSCCs. We observed a statistically significant positive correlation between frequency of FHIT loss and increasing grade of dysplasia (m 2 = 13.8; degrees of freedom = 4; P = 0.008). Loss of FHITexpression in POLs that progressed to malignancy was more frequent than in those that did not [17 of 25 (68%) versus 12 of 29 (41.4%), respectively]. This difference was statistically significant (m 2 = 3.8; degrees of freedom = 1; P = 0.046). In OSCCs, loss of FHIT staining indicated a worse prognosis (survival rate, 36.2%) than when positive FHIT staining was observed (survival rate, 50%), but the difference was not statistically significant (P = 0.546, Kaplan-Meier, log-rank). Conclusions: FHITseems to localize to both nuclear and cytoplasmic domains. FHIT inactivation occurs early in oral carcinogenesis and may be useful molecular marker for progressive dysplastic oral lesions.

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Section: Discussionmentioning

confidence: 99%

Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Kujan

Oliver

Roz

et al. 2006

Clinical Cancer Research

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“…17 The tumor suppressor gene fragile histidine triad (FHIT) spans the FRA3B fragile site, 18 and abnormal FHIT transcription and low FHIT expression were detected in various human cancers, including oral squamous cell carcinomas. 19,20 Studies of the two most frequently affected common fragile site loci, FRA3B and FRA16D, have provided compelling evidence that these regions are indeed prone to DNA instability in cancer cells. 21 It has also been shown that exposure to environmental carcinogens such as smoking and alcohol consumption increases the potential for chromosome breakage at fragile sites FRA3B and FRA16D in esophageal, non-small-cell lung and cutaneous squamous cancer.…”

Section: Introductionmentioning

confidence: 99%

Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias

et al. 2008

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SummaryOral leukoplakia is the most prevalent and potentially malignant disorder of the oral mucosa. Previous studies have demonstrated that molecular changes of the WWOX gene (WW-domain containing oxidoreductase), a candidate tumor suppressor gene located at 16q23.3-24.1 that spans FRA16D, the second most common fragile site, are present in several malignant neoplasias, including oral squamous cell carcinoma. In this report, the role of the WWOX gene was investigated in 23 cases of oral leukoplakias. Using nested RT-PCR and immunohistochemistry, altered mRNA transcription and/or reduced Wwox protein expression was observed in 35% of the lesions when compared with normal mucosa. The majority of lesions (4/6) with altered transcripts had a reduction in the expression of Wwox protein. Although normal WWOX expression was found in some lesions with dysplasia, all lesions with WWOX mRNA and/or protein expression showed histological evidence of dysplasia and none of the cases without dysplasia presented this alteration. These results show that the WWOX gene alteration is an early genetic alteration and may contribute to oral carcinogenesis.

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“…It has been reported that the risk of distant metastasis is higher, but not statistically significant, yet as loco regional recurrence is cross-referenced, it was found to be rare in patients with FHIT expression loss. It has been argued that in patients with FHIT expression loss, sensitivity to radiotherapy is higher, hence loco regional recurrence is lower [22]. It has thus been concluded that the tumors in patients with decreasing FHIT expression are radiosensitive.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Fhit and Wwox Proteins Expression in Laryngeal Cancer

G¹

2013

Otolaryngology

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Loss of Fhit Expression in Head and Neck Squamous Cell Carcinoma and Its Potential Clinical Implication

Abstract: ABSTRACT

Cited by 21 publications

References 21 publications

Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias

Prognostic Significance of Fhit and Wwox Proteins Expression in Laryngeal Cancer

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