Long-term histopathological changes of the nasal mucosa after total laryngectomy: a prospective cohort study.

BACKGROUND: Changes in the nasal function following total laryngectomy resulted in histopathological alterations of the nasal mucosa. We aimed to evaluate the long-term histopathological changes and the mucociliary clearance (MCC) of the nasal mucosa after total laryngectomy. METHODS: We performed a histological examination of inferior turbinate biopsy, and saccharine test to assess the MCC time for patients who were candidates for total laryngectomy before the procedure, 6-12 months after surgery, and at least two years postoperatively. RESULTS: Seventy-five patients scheduled for total laryngectomy were initially enrolled in our study. We excluded patients who received postoperative radiotherapy or were lost during the follow-up period. Eventually, 63 and 54 patients were available for assessment 6-12 months after surgery and at least two years postoperatively, respectively. Except for ciliary and goblet cell destruction, which were significantly reduced 6-12 months postoperatively, there were no statistically significant differences in the histopathological findings of the nasal mucosa before surgery and 6-12 months postoperatively. After two years, the histopathological alterations of the nasal mucosa were statistically more evident than those before surgery and 6-12 months postoperatively; the most common histopathological findings were mononuclear cell infiltration and stromal fibrosis. The mean MCC time preoperatively was 12.56 minutes that statistically significantly decreased to 11.81 minutes 6-12 months after surgery; then, it significantly increased to 20.98 minutes at least two years postoperatively. CONCLUSIONS: After total laryngectomy, the nasal mucosa showed histopathological alterations and early enhancement of the MCC, which was later impaired due to nasal mucosal atrophy and the saprophytic infection.

Magnetic resonance imaging features of hip disorders in an Egyptian pediatric population.

Hip disorders in a pediatric population are a diagnostic challenge. The aim of the study is to assess the role of magnetic resonance imaging (MRI) in the evaluation of non-traumatic hip disorders in a series of Egyptian patients and to review the literature on the most common hip conditions. Seventy two consecutive patients [40 males (55.6%) and 32 females (44.4)] with acute onset of hip complaints unrelated to trauma or falls were recruited. All patients underwent an initial full clinical assessment and blood tests as well as contrast enhanced MRI of both hips. The most common diagnosis in this group of Egyptian patients was transient synovitis in 29 (40.3%) cases, followed by seronegative enthesopathy and arthropathy syndrome in 8 (11.1%), septic arthritis in 10 (13.9%), tuberculous arthritis in 4 (5.6%), sickle-cell disease in 7 (9.7%), complicated with septic arthritis in 3 (4.2%), transient bone marrow edema (BME) in 3 (4.2%), osteomyelitis in 2 (2.8%), osteosarcoma in 2 (2.8%), sciatic nerve injury in 1 (1.4%), leukemia with BME in 1 (1.4%), coxa vara of both hips and L5/S1 facet joint ankylosis in 1 (1.4%), and a benign bone cyst in 1 (1.4%). MRI studies showed hip effusion in a total of 51 patients (70.8%), joint space narrowing in 9 (12.5%), and BME in 15(20.8%). MRI is a sensitive tool for assessing hip disorders in a pediatric population and can play an important role in both diagnosis and management of different hip disorders, irrespective of the underlying pathology.

Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts.

BACKGROUND: Myelodysplastic syndromes are a diverse and common group of chronic hematologic cancers. The identification of new genetic lesions could facilitate new diagnostic and therapeutic strategies. METHODS: We used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in 9 patients with low-grade myelodysplasia. Targeted resequencing of the gene encoding RNA splicing factor 3B, subunit 1 (SF3B1), was also performed in a cohort of 2087 patients with myeloid or other cancers. RESULTS: We identified 64 point mutations in the 9 patients. Recurrent somatically acquired mutations were identified in SF3B1. Follow-up revealed SF3B1 mutations in 72 of 354 patients (20%) with myelodysplastic syndromes, with particularly high frequency among patients whose disease was characterized by ring sideroblasts (53 of 82 [65%]). The gene was also mutated in 1 to 5% of patients with a variety of other tumor types. The observed mutations were less deleterious than was expected on the basis of chance, suggesting that the mutated protein retains structural integrity with altered function. SF3B1 mutations were associated with down-regulation of key gene networks, including core mitochondrial pathways. Clinically, patients with SF3B1 mutations had fewer cytopenias and longer event-free survival than patients without SF3B1 mutations. CONCLUSIONS: Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes. (Funded by the Wellcome Trust and others.).

Urban legends series: oral leukoplakia.

To date, the term oral leukoplakia (OL) should be used to recognize 'predominantly white plaques of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk of cancer'. In this review, we addressed four controversial topics regarding oral leukoplakias (OLs): (i) Do tobacco and alcohol cause OLs?, (ii) What percentage of OLs transform into oral squamous cell carcinoma (OSCC)?, (iii) Can we distinguish between premalignant and innocent OLs?, and (iv) Is proliferative verrucous leukoplakia (PVL) a specific entity or just a form of multifocal leukoplakia? Results of extensive literature search suggest that (i) no definitive evidence for direct causal relationship between smoked tobacco and alcohol as causative factors of OLs, (ii and iii) the vast majority of OLs follow a benign course and do not progress into a cancer, and no widely accepted and/or validated clinical and/or biological factors can predict malignant transformation, and (iv) the distinction between multifocal/multiple leukoplakias and PVL in their early presentation is impossible; the temporal clinical progression and the high rate of recurrences and development of cancer of PVL are the most reliable features for diagnosis.

Development of Perovskite (MACl)0.33FA0.99MA0.01Pb(I0.99Br0.01)3 Solar Cells via n-Octylammonium Iodide Surface Passivation.

The influence of n-octylammonium iodide (OAI, passive layer) on the types of phases formed in a (MACl)0.33FA0.99MA0.01Pb(I0.99Br0.01)3 perovskite film was studied using X-ray diffraction. Using UV spectrophotometric techniques, it was determined how varied OAI additive layer ratios affected the linear and nonlinear optical characteristics of glass substrates/FTO/compact TiO2/mesoporous TiO2/(MACl)0.33FA0.99MA0.01Pb(I0.99Br0.01)3 films. All films' direct optical bandgap energies were determined to be 1.54 eV. The effects of OAI addition on the films' photoluminescence intensity and emitted colors were also investigated. For the fabricated perovskite solar cells (PSCs) without an OAI passivation layer, the corresponding power conversion efficiency (PCE), open-circuit voltage (VOC), short-circuit current density (JSC), and fill factor (FF) values were 18.8%, 1.02 V, 24.6 mAcm-2, and 75%, respectively. When the concentration of OAI reached 2 mg, the maximum obtained values of PCE, VOC, JSC, and FF were 20.2%, 1.06 V, 24.2 mAcm-2, and 79%, respectively. The decreased trap density and increased recombination resistance were responsible for the improvement in solar cell performance.

Structural, Optical, and Electrical Parameters of Doped PVA/PVP Blend with TPAI or THAI Salt.

The 70% polyvinyl alcohol/30% polyvinyl pyrrolidone (PVA/PVP) polymer blends, with different weight ratios of tetrapropylammonium iodide (TPAI) or tetrahexylammonium iodide (THAI) salt, were prepared using dimethyl sulfoxide (DMSO) as a solvent. The X-ray diffraction technique was used to trace the crystalline nature of the formed blends. The SEM and EDS techniques were applied to figure out the morphology of the blends. The variation in the FTIR vibrational bands was used to investigate the chemical composition and the effect of different salt doping on the functional groups of the host blend. The influence of the salt type (TPAI or THAI) and its ratio on the linear and nonlinear optical parameters for the doped blends were investigated in detail. Absorbance and reflectance are highly enhanced in the UV region reaching a maximum for the blend with 24% TPAI or THAI; so, it can be employed as shielding materials for UVA and UVB types. The direct (5.1 eV) and indirect (4.8 eV) optical bandgaps were reduced continuously to (3.52, 3.63 eV) and (3.45, 3.51 eV) while increasing the content of TPAI or THAI, respectively. The blend doped with 24% wt TPAI exhibited the highest refractive index (around 3.5 in 400-800 nm). The DC conductivity is affected by the content and type of salt, its dispersion, and blend-salt interaction. The activation energies of different blends were obtained by applying the Arrhenius formula.

Impact of ZnS/Mn on the Structure, Optical, and Electric Properties of PVC Polymer.

The most efficient way to create novel materials that may be used in a variety of optoelectronic applications is thought to be doped mixed polymers with appropriate fillers. Undoped and doped PVC polymers with ZnS/Mn formed at different temperatures were fabricated using the casting method. The Rietveld method was used to discover the structure and microstructure of Zn0.95Mn0.05S prepared at T = 300, 400, and 500 °C. The distribution and existence of the nanofiller over the PVC matrix were determined via XRD, FTIR, EDS, and SEM techniques. The effect of the preparation temperatures of the ZnS/Mn nanofiller on the absorption, transmittance, reflectance, refractive index, extinction coefficient, dielectric constant, AC conductivity, electrical modulus, and DC conductivity activation energy data of the PVC polymer was studied using the diffused reflectance technique. Doping PVC with ZnS/Mn (prepared at 300 °C) lowered the direct and indirect optical band gaps from 5.4 and 4.52 eV to minimum values of 4.55 and 3.63 eV. The fluorescence intensity of pure PVC is greatly enhanced upon loading with ZnS/Mn. The PVC exhibited two near UV peaks, one violet and one blue color, while, in addition, the doped polymers exhibited green and orange colors. The corresponding CIE diagram for all the samples was also determined.

Third window approach assisted middle meatal antrostomy: prospective cohort study of the two ports technique in management of hard to reach maxillary sinus pathology.

OBJECTIVE: This study aimed to assess the outcomes of a prelacrimal recess approach assisted middle meatal antrostomy in the management of hard to reach maxillary sinus pathologies. METHOD: Twenty-five patients with maxillary sinus pathology underwent prelacrimal recess approach assisted middle meatal antrostomy (with a prelacrimal recess width of more than 3 mm). Patients were prospectively evaluated using both the Arabic version of the Sino-Nasal Outcome Test-22 and nasal endoscopy at least 6 months post-operatively. RESULTS: Our study included 25 maxillary sinuses (13 with antrochoanal polyps, 10 with maxillary fungal ball and 2 with a migrated part of a tooth). At a mean follow-up period of 10.9 months, all patients showed significant improvement in total mean Sino-Nasal Outcome Test-22 score. There was recurrence of one case with antrochoanal polyp and two cases with asymptomatic synechia. Injury to the nasolacrimal duct was not reported. CONCLUSION: A prelacrimal recess approach assisted middle meatal antrostomy is a reliable and safe technique to manage pathologies in hard to reach regions within the maxillary sinus.

A genetic mouse model for metastatic lung cancer with gender differences in survival.

Lung cancer is a devastating disease with poor prognosis. The design of better therapies for lung cancer patients would be greatly aided by good mouse models that closely resemble the human disease. Unfortunately, current models for lung adenocarcinoma are inadequate due to the absence of metastases. In this study, we incorporated both K-ras and p53 missense mutations into the mouse genome and established a more faithful genetic model for human lung adenocarcinoma, the most common type of lung cancer. Mice with both mutations developed advanced lung adenocarcinomas that were highly aggressive and metastasized to multiple intrathoracic and extrathoracic sites in a pattern similar to that of human lung cancer. These mice also showed a gender difference in cancer-related death. Additionally, the presence of both mutations induced pleural mesotheliomas in 23% of these mice. This mouse model recapitulates the metastatic nature of human lung cancer and will be invaluable to further probe the molecular basis of metastatic lung cancer and for translational studies.

Contrasting effects of an Mdm2 functional polymorphism on tumor phenotypes.

MDM2, an E3 ubiquitin ligase, is a potent inhibitor of the p53 tumor suppressor and is elevated in many human cancers that retain wild-type p53. MDM2 SNP309G is a functional polymorphism that results in elevated levels of MDM2 (due to enhanced SP1 binding to the MDM2 promoter) thus decreasing p53 activity. Mdm2SNP309G/G mice are more prone to spontaneous tumor formation than Mdm2SNP309T/T mice, providing direct evidence for the impact of this SNP in tumor development. We asked whether environmental factors impact SNP309G function and show that SNP309G cooperates with ionizing radiation to exacerbate tumor development. Surprisingly, ultraviolet B light or Benzo(a)pyrene exposure of skin shows that SNP309G allele actually protects against squamous cell carcinoma susceptibility. These contrasting differences led us to interrogate the mechanism by which Mdm2 SNP309 regulates tumor susceptibility in a tissue-specific manner. Although basal Mdm2 levels were significantly higher in most tissues in Mdm2SNP309G/G mice compared with Mdm2SNP309T/T mice, they were significantly lower in Mdm2SNP309G/G keratinocytes, the cell-type susceptible to squamous cell carcinoma. The assessment of potential transcriptional regulators in ENCODE ChIP-seq database identified transcriptional repressor E2F6 as a possible negative regulator of MDM2 expression. Our data show that E2F6 suppresses Mdm2 expression in cells harboring the SNP309G allele but not the SNP309T allele. Thus, Mdm2 SNP309G exhibits tissue-specific regulation and differentially impacts cancer risk.

Blood Hematological and Biochemical Constituents, Antioxidant Enzymes, Immunity and Lymphoid Organs of Broiler Chicks Supplemented with Propolis, Bee Pollen and Mannan Oligosaccharides Continuously or Intermittently.

This study investigate the effect of bee pollen (BP) and/or propolis (Pro) as an alternative to Mannan oligosaccharides (Bio-MOS, a hydrolyzed yeast with natural and artificial flavors Alltech Inc) when given continuously or intermittently on antioxidant enzymes, immunity, weight and morphology of lymphoid organs of broilers. Thus, 324 unsexed one-day-old Arbor Acres broilers were randomly distributed into nine treatment groups, each replicated 6 times of 6 birds per replicate. The chicks were kept in wire cages and fed the same basal diet and were submitted to the following treatments: control without supplementation (control) or supplemented with BP at 300 mg, Pro at 300 mg, BP+Pro at 300 mg each and Bio-MOS at 0.5 g/kg diet. Each supplemented group was subdivided into two subgroups in which the additives were supplied continuously or intermittently. In the continuously supplemented groups, supplementations were given from one till 36 days of age, and in the intermittently supplemented groups, the administration was only three days before, on the day of and day after vaccination. The BP and Pro supplied continuously or intermittently was equally potent for improving immunity, antioxidant enzymes similar to Bio-MOS. All supplements supplied either continuously or intermittently resulted a significantly higher thymus (P < .04) and bursa weights (P < .001) than the control group. Combining BP with Pro resulted in a further increase in thymus weights and small follicle diameter compared to the control group. In addition, thymus percentage in the group received BP+Pro showed a further increase compared to the control and Pro supplemented intermittently. Bio-MOS, when supplied continuously or intermittently, resulted in the greatest response in splenic lymphoblasts. Supplementation with either BP or Pro intermittently, is adequate to promote health and immune response of broiler chicks, with 40% saving of supplementation costs.

Phenotype and genotype of advanced premalignant head and neck lesions after chemopreventive therapy.

BACKGROUND: The goal of chemoprevention is to reduce the risk of cancer development by reversing or blocking the tumorigenic process through the use of pharmacologic or natural agents. To determine the potential role of genetic alterations in assessing cancer risk and in evaluating the efficacy of chemopreventive agents, we studied 22 patients with advanced premalignant lesions of the head and neck who were part of a prospective cancer prevention trial that is investigating a regimen of 13-cis-retinoic acid, interferon alfa, and alpha-tocopherol administered for 12 months or until disease progression. METHODS: We used polymerase chain reaction analysis of microsatellite DNA sequences in cells from precancerous lesions to determine the frequencies of genetic alterations--namely, loss of heterozygosity (LOH) and microsatellite instability--at chromosomal loci that are commonly deleted in head and neck cancer. RESULTS: Prior to treatment, 17 (81%) of 21, eight (44%) of 18, and eight (42%) of 19 patients who were informative (i.e., heterozygous) at chromosomes 9p21, 3p14, and 17p13, respectively, exhibited LOH in at least one of their lesion biopsy specimens. Among nine patients who exhibited LOH at chromosome 9p21 in pretreatment biopsy specimens and who had completed at least 5 months of therapy, the genetic loss persisted in eight--including three of the four patients who exhibited complete histologic responses (i.e., no evidence of dysplasia in their biopsy specimens). IMPLICATION: Our data suggest that clinical and histologic assessments of the response to chemopreventive agents may be insufficient to determine their efficacy and that critical genetic alterations could be used as independent biomarkers to augment the ability to evaluate the efficacy of such agents.

Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer.

BACKGROUND: Preclinical studies in animal models have demonstrated tumor regression following intratumoral administration of an adenovirus vector containing wild-type p53 complementary DNA (Ad-p53). Therefore, in a phase I clinical trial, we administered Ad-p53 to 28 patients with non-small-cell lung cancer (NSCLC) whose cancers had progressed on conventional treatments. METHODS: Patients received up to six, monthly intratumoral injections of Ad-p53 by use of computed tomography-guided percutaneous fine-needle injection (23 patients) or bronchoscopy (five patients). The doses ranged from 10(6) plaque-forming units (PFU) to 10(11) PFU. RESULTS: Polymerase chain reaction (PCR) analysis showed the presence of adenovirus vector DNA in 18 (86%) of 21 patients with evaluable posttreatment biopsy specimens; vector-specific p53 messenger RNA was detected by means of reverse transcription-PCR analysis in 12 (46%) of 26 patients. Apoptosis (programmed cell death) was demonstrated by increased terminal deoxynucleotide transferase-mediated biotin uridine triphosphate nick-end labeling (TUNEL) staining in posttreatment biopsy specimens from 11 patients. Vector-related toxicity was minimal (National Cancer Institute's Common Toxicity Criteria: grade 3 = one patient; grade 4 = no patients) in 84 courses of treatment, despite repeated injections (up to six) in 23 patients. Therapeutic activity in 25 evaluable patients included partial responses in two patients (8%) and disease stabilization (range, 2-14 months) in 16 patients (64%); the remaining seven patients (28%) exhibited disease progression. CONCLUSIONS: Repeated intratumoral injections of Ad-p53 appear to be well tolerated, result in transgene expression of wild-type p53, and seem to mediate antitumor activity in a subset of patients with advanced NSCLC.

Variable expression of cytokines in human head and neck squamous cell carcinoma cell lines and consistent expression in surgical specimens.

Head and neck squamous cell carcinomas (HNSCCs) are associated with abnormal cell-mediated immunity at the primary tumor site. We investigated tumor-derived cytokines as factors underlying such abnormalities. Cytokine mRNA and protein of eight HNSCC-derived cell lines were tested; reverse transcription-PCR results indicated the presence of mRNAs for interleukin 1alpha (IL-1alpha) and transforming growth factor alpha (8 of 8); transforming growth factor beta and IL-1beta (7 of 8); and IL-4 and IL-6 (4 of 8). IL-2, IFN-gamma, and tumor necrosis factor alpha mRNA were not detected. Supernatants from six of these cell lines were analyzed by ELISA; IL-1alpha, IL-1beta, and IL-6 were found to be markedly increased compared to human papillomavirus-16-immortalized human oral keratinocytes. To determine whether the cell line findings are applicable to primary tumors, we performed immunohistochemical analysis on tumor specimens from 12 patients with invasive HNSCC. Universal intracellular production of IL-1alpha, IL-1beta, and IL-6 protein was detected. We conclude that the aberrant elaboration of biologically active IL-1 and IL-6 may contribute to altered immune status in HNSCC patients.

Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival.

Few molecular genetic alterations have been identified in endometrial cancers that are associated with poor clinical outcome. Overexpression of HER-2/neu, transforming growth factor alpha, and p53 proteins have all been associated with poor prognosis in women with endometrial cancer. In this study, the level of HER-2/neu gene amplification and expression was characterized in 92 endometrial cancers. Fluorescence in situ hybridization (FISH) was used to characterize HER-2/neu gene copy number, and immunohistochemistry was used to characterize expression. Forty-seven of the 90 (52%) endometrial cancers were characterized as showing moderate or high immunostaining. HER-2/neu gene amplification was detected in 17 of 81 (21%) cases. Immunohistochemical staining and FISH results were both available for 80 cases. Fourteen of these cases showed both moderate or high immunostaining and gene amplification. Clinical follow-up information was available for 76 women in this study. Women whose endometrial cancer exhibited HER-2/neu gene amplification by FISH had a shorter overall survival than women whose endometrial cancer lacked amplification (P = 0.018). Likewise, tumors with moderate or high HER-2/neu immunostaining were associated with a lower cumulative overall survival than tumors with low immunostaining by log rank analysis (P < 0.0001). Multivariate analysis of survival rates revealed HER-2/neu overexpression to be an independent predictor of overall survival (P = 0.0163). Among those patients with HER-2/neu overexpression, adjuvant chemotherapy or radiation therapy was associated with an improved overall survival (P = 0.039). However, among those women whose tumor lacked overexpression, overall survival was not improved by adjuvant treatment.

Sequential loss of heterozygosity at microsatellite motifs in preinvasive and invasive head and neck squamous carcinoma.

Studies of sequential molecular alterations in noninvasive and invasive head and neck squamous carcinoma are few in number. Consequently, the genetic changes associated with the neoplastic transformation of these carcinomas have not been defined. To identify chromosomal alterations in preinvasive and invasive head and neck squamous carcinoma, we analyzed DNA from microdissected normal squamous epithelium, severe dysplasia, and invasive carcinoma samples from 20 patients for loss of heterozygosity (LOH) at microsatellite loci by multiplex PCR. Twenty-five microsatellite repeats on chromosomes 3p, 5q, 8p, 9p and 9q, 11q, 17p, 17q, and 18p and 18q regions were used. In informative cases, LOH in noninvasive lesions was observed in 9p (28%), 9q and 18q (10%), 11q and 17p (7%), and 3p and 18p (5%). A high incidence of LOH in invasive carcinoma was observed at 9p (72%), 8p (53%), 3p (47%), 9q (35%), and 11q (33%). LOH was also associated with DNA aneuploidy, high tumor stage, and poor histological differentiation. Our results indicate that: (a) the high incidence of LOH at loci on chromosomes 9p, 8p, 3p, 9q, and 11q implicate these regions in head and neck squamous carcinoma tumorigenesis; (b) 9p loci alterations are manifested in the early development of these tumors; (c) LOH is correlated with poor prognostic clinicopathological factors; and (d) LOH at 8p loci appears to be associated with the tumor's aggressive features.

The genetic locus NRC-1 within chromosome 3p12 mediates tumor suppression in renal cell carcinoma independently of histological type, tumor microenvironment, and VHL mutation.

Human chromosome 3p cytogenetic abnormalities and loss of heterozygosity have been observed at high frequency in the nonpapillary form of sporadic renal cell carcinoma (RCC). The von Hippel-Lindau (VHL) gene has been identified as a tumor suppressor gene for RCC at 3p25, and functional studies as well as molecular genetic and cytogenetic analyses have suggested as many as two or three additional regions of 3p that could harbor tumor suppressor genes for sporadic RCC. We have previously functionally defined a novel genetic locus nonpapillary renal carcinoma-1 (NRC-1) within chromosome 3p12, distinct from the VHL gene, that mediates tumor suppression and rapid cell death of RCC cells in vivo. We now report the suppression of tumorigenicity of RCC cells in vivo after the transfer of a defined centric 3p fragment into different histological types of RCC. Results document the functional involvement of NRC-1 in not only different cell types of RCC (i.e., clear cell, mixed granular cell/clear cell, and sarcomatoid types) but also in papillary RCC, a less frequent histological type of RCC for which chromosome 3p LOH and genetic aberrations have only rarely been observed. We also report that the tumor suppression observed in functional genetic screens was independent of the microenvironment of the tumor, further supporting a role for NRC-1 as a more general mediator of in vivo growth control. Furthermore, this report demonstrates the first functional evidence for a VHL-independent pathway to tumorigenesis in the kidney via the genetic locus NRC-1.

Loss of Fhit expression is a predictor of poor outcome in tongue cancer.

Abnormalities of FHIT, a candidate tumor suppressor gene located at 3pl4.2, have been found frequently in multiple tumor types, including head and neck squamous cell carcinoma. To determine the role of FHIT in tongue cancers, Fhit expression was determined by immunohistochemistry studies in tissue samples from 41 patients with stages II-IV squamous cell carcinomas of the tongue. All of the patients underwent curative surgical treatment with a median of 83 months of follow-up care. We found that 28 (68%) of the 41 tumor specimens demonstrated a lack of or significantly decreased staining for Fhit. Fhit expression tended to be stronger in well-differentiated tumor areas than it was in poorly differentiated areas, although this trend was not statistically significant. There was no significant correlation between Fhit expression and a patient's age or sex or the histological grade or clinical stage of disease. As expected, clinical stage and nodal involvement correlated with prognosis. Interestingly, patients whose tumors demonstrated low levels of or no Fhit expression had a significantly shorter time of disease-free survival than those whose tumors had high Fhit expression (P = 0.035, by log-rank test). This prognostic value of Fhit was independent of other clinical parameters, including stage of disease and nodal status. We conclude that Fhit plays an important role in the development of squamous cell carcinomas of the tongue and that loss of Fhit expression may be an independent prognostic indicator for clinical outcome in patients with this tumor type.