[Is effective a shortened surveillance system of bloodstream infection?]. / Es eficaz un sistema de vigilancia acortado en las infecciones del torrente sanguíneo?

INTRODUCTION: Surveillance is necessary for bloodstream infection control. Daily monitoring of the central venous catheter (CVC) use, a time-demanding process, is the standard denominator to calculate the infection rate; surveillance of only one day per week has been proposed as alternative. OBJECTIVE: To determine whether surveillance of one day per week is similar to daily monitoring in a second-level hospital. MATERIAL AND METHODS: Daily monitoring of CVC utilization ratio was done during nine weeks in four locations of a second-level hospital. For each day, proportional differences respect to the global CVC utilization ratio was estimated. An ANOVA test was done to find differences between each weekday. RESULTS: CVC usage surveillance was performed for 9 weeks, so nine determinations were obtained for each weekday. No significant differences were found between each day (F = 2.20, p = 0.056). The lowest sampling discrepancy was found on Wednesdays. CONCLUSIONS: According to previous studies, and our own data, monitoring the CVC use one day per week is a reasonable alternative to the daily surveillance.

Warthin adenocarcinoma: analysis of 2 cases of a distinct salivary neoplasm.

Carcinomas arising in or from the epithelial component of preexisting parotid Warthin tumors (WTs) are rare; the other histologic types of carcinoma found to arise from WTs are adenocarcinoma not otherwise specified, undifferentiated, mucoepidermoid, squamous cell, and oncocytic. The aim of this study is to describe the clinicopathologic features of a distinct salivary gland neoplasm, previously undescribed, with a striated duct phenotype arising from WT. We have designated this neoplasm "Warthin adenocarcinoma" (WA). In this retrospective study, we searched the surgical pathology files of the Department of Pathology at The University of Texas M.D. Anderson Cancer Center for cases of malignant WT and salivary adenocarcinoma not otherwise specified diagnosed from January 1, 1985, through December 31, 2006, and evaluated patients' medical records and pathologic material. We obtained tissue sections and immunohistochemically stained them with antibodies against p63; Bcl-2; cytokeratin (CK)903, CK7, CK14, and CK18; antimitochondrial antibody (AMA); smooth muscle actin; calponin; S-100; and Ki-67. We identified 2 cases of WA; both patients were women, 44 and 60 years of age, with 4.0- and 4.5-cm tumors in the left parotid gland. Histologically, the tumors were composed of bilayered duct-like structures: The inner layer was formed by a single row of columnar oxyphilic cells expressing CK7, CK14, CK18, and AMA. The outer layer was composed of multiple layers of small round dark cells with scanty cytoplasm that expressed p63, Bcl-2, and CK903 and were focally positive for AMA and negative for myoepithelial markers. The Ki-67 proliferative indices were 20%; and 25%. A residual WT with transition to carcinoma was identified in both cases. Treatment had consisted of total parotidectomy with postoperative irradiation. Patients were free of disease 1 and 3 years after treatment. Warthin adenocarcinoma is a unique salivary gland carcinoma representing the malignant epithelial counterpart of WT. The identification of additional cases would help to better elucidate the line of differentiation of the tumor and further define its natural history.

Clinical features and differential diagnoses of solitary extramedullary plasmacytoma of the thyroid: a case report.

A 40-year-old woman presented with a rapidly enlarging palpable thyroid mass. The patient underwent a total thyroidectomy. The tumor fulfilled the criteria of primary solitary extramedullary plasmacytoma (SEP), including cellular expression of the CD138 and lambda light chain antibodies. Solitary extramedullary plasmacytoma of the thyroid occurs most commonly in patients with Hashimoto thyroiditis and must be distinguished from involvement of thyroid in multiple myeloma, inflammatory pseudotumor plasma cell variant, mucosa-associated lymphoid tissue lymphoma, and medullary carcinoma. The distinction is determined on the basis of histologic findings, immunohistochemical analysis, and other laboratory tests. Currently, no standard treatment exists for this entity. In this report, we discuss the differential diagnosis of SEP of the thyroid and the clinical features observed in this case.

Sinonasal chondromyxoid fibroma.

Chondromyxoid fibroma (CMF) is a rare benign cartilaginous tumor that usually arises from the metaphysis of long bones. In rare cases, however, CMF presents in unusual locations, such as the facial bones and sinonasal tract. We present a case of a 60-year-old woman with a CMF of the nasal septum. The initial radiographic findings were suggestive of a vascular tumor or a malignancy, but microscopic examination revealed the typical pathologic features of CMF, and SOX9 immunostaining confirmed its cartilaginous origin. The tumor was successfully excised, and the patient was free of disease at 12-month follow-up. Recognizing CMF is important when it presents in unexpected locations, especially because of its histologic resemblance to chondrosarcoma. We believe that the use of SOX9 in our case assisted in the recognition of the chondroid nature of the lesion and facilitated the diagnosis of CMF.

Thyrolipoma and thyrolipomatosis: 5 case reports and historical review of the literature.

Because thyrolipoma (adenolipoma of thyroid) and thyrolipomatosis (diffuse lipomatosis of thyroid) are distinctively rare conditions with only few cases reported in the literature, we are reporting 5 additional cases. All the 5 patients were adult females, with ages from 38 to 79 years, who presented with thyroid masses. Four of the patients had normal thyroid function tests and one had mild hypothyroidism. All patients received partial or total thyroidectomy. The thyroid specimens showed either circumscribed yellow-tan masses (cases 1, 2, and 3) or diffuse yellow-brown discoloration (cases 4 and 5). Histologic examination revealed abundant mature fat infiltrating the affected thyroid tissue in 3 distinct patterns: (1) fat infiltration limited to follicular adenomas (thyrolipoma); (2) fat diffusely infiltrating throughout the thyroid gland (thyrolipomatosis); or (3) fat infiltration involving both follicular adenoma and their surrounding thyroid tissue. Because of the rarity of thyroid fat-containing lesions, confusion in differential diagnosis may occasionally occur. It is important to be aware during frozen section that these lesions may present as extrathyroidal nodules, which can be radioactive on intraoperative scan for parathyroid glands. In addition, a papillary thyroid carcinoma was also identified in one case of thyrolipomatosis. All patients recovered well after surgery and there has been no recurrence of the lesions after 1 to 24 years of clinical follow-up. In summary, we are reporting 5 rare cases of thyrolipoma and thyrolipomatosis with distinct histologic patterns. Previously reported cases of thyrolipomatosis were reviewed and analyzed with the current cases.

Primary sinonasal choriocarcinoma.

Primary choriocarcinoma of sinonasal tract has not been previously documented. The aim of the study was to report, for the first time, 2 cases of primary sinonasal choriocarcinoma. The differential diagnosis is discussed and also the theories concerning the histogenesis of this neoplasm are briefly reviewed. Two male patients of 44 and 49 years of age complained of epistaxis and nasal obstruction of 2-week duration. Computerized axial tomographic scan of the head revealed an opacity of the left nasal cavity in one patient and a destructive lesion of the maxillary sinus in the other. Histopathologically, the lesions disclosed a dual cell population composed of cytotrophoblastic cells with uniform, round nuclei, clear cytoplasm, admixed with large multinucleated syncytiotrophoblastic cells, with bizarre nuclei, and abundant eosinophilic cytoplasm. Immunohistochemically, the tumors were notable for strong keratin and beta-chorionic gonadotrophin (HCG) positivity. The serum levels of HCG were 13 000 and 779 mIU/mL, respectively. One patient treated with maxillectomy, postoperative radiotherapy, and 5 courses of VIP chemotherapy (cisplatinum, etoposide, ifosfomide) died with brain metastases 10 months after diagnosis. The other patient received 4 courses of etoposide, and he is alive without tumor, 10 months after diagnosis. The serum levels of HCG are still negative. The present cases demonstrated the widespread distribution of germ cell tumors in the human body and lead to further support of the existence of primary choriocarcinomas in the sinonasal tract. Correct identification of this neoplasm is therefore important for institution of specific therapy.

CRTC1/MAML2 fusion transcript in Warthin's tumor and mucoepidermoid carcinoma: evidence for a common genetic association.

Translocations and gene fusions have an important early role in tumorigenesis. The t(11;19) translocation and its CRTC1/MAML2 fusion transcript have been identified in several examples of both Warthin's tumor and mucoepidermoid carcinoma and are believed to be associated with the development of a subset of these tumors. To determine whether Warthin's tumor and mucoepidermoid carcinoma are genetically related, we used reverse transcriptase-polymerase chain reaction and DNA sequencing to analyze microdissected components of three tumors consisting of Warthin's tumor and mucoepidermoid carcinoma. We also investigated a metastatic melanoma to Warthin's tumor and a Warthin's carcinoma of the parotid gland for comparison. The fusion transcript was identified in both Warthin's tumor and matching mucoepidermoid carcinoma components of all three tumors, in the Warthin's carcinoma, and in the Warthin's tumor component but not in the metastatic melanoma. The results provide evidence for a link between the t(11;19) fusion gene and the development of a subset of Warthin's tumors with concurrent mucoepidermoid carcinoma and possible malignant transformation to Warthin's carcinoma. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

Eosinophil-rich squamous carcinoma of the oral cavity: a study of 13 cases and delineation of a possible new microscopic entity.

We report 13 cases of squamous cell carcinoma (SCC) of the oral cavity characterized by a prominent eosinophilic infiltration of the stroma. All patients were adults, 10 men and 3 women (aged 54 to 92 years; median, 71 years). They presented with tumors of the gingiva (5 cases), tongue (3 cases), palatine tonsil (2 cases), palate (2 cases), and mucosal aspect of lip (1 case). Metastatic involvement of regional lymph nodes was seen in 5 cases. The metastatic foci were associated with heavy eosinophilia as well. No patient had an abnormal eosinophil count in blood. Microscopically, the clusters of eosinophils were characteristically noticed in intimate admixture with the advancing edge of squamous carcinoma, either as nests or small tumor cords. The pattern of eosinophilic infiltration was comparable, regardless of tumor site or grade. Data from our series indicate that SCC with a reactive inflammatory infiltrate rich in eosinophils is consistently associated with stromal invasion. This observation may be useful in dealing with small tissue fragments where subepithelial stromal invasion cannot be easily assessed by conventional criteria. In addition, our data seem to confirm that eosinophil-rich SCC, although associated with metastatic involvement of cervical lymph node, seems to pursue a less aggressive course if compared with ordinary SCC.

Eosinophilic angiocentric fibrosis of the sinonasal tract.

Eosinophilic angiocentric fibrosis (EAF) is an uncommon inflammatory fibrosing lesion of the upper respiratory tract and orbit that occurs mainly in young to middle-aged women. The etiology of EAF is unknown. To our knowledge, approximately 28 cases have been previously reported in the English literature. We report here 3 additional cases of EAF of the sinonasal tract; 2 in women aged 19 and 31 years, and 1 in a man aged 49 years. The 19-year-old woman is the youngest patient with EAF ever described. The patients presented with a nasal cavity mass, face pain, or nasal obstructive symptoms of long duration.

Cytomegalovirus infection in patients with lymphoma: an important cause of morbidity and mortality.

BACKGROUND: Cytomegalovirus (CMV) antigenemia (CMV-A) and CMV disease (CMV-D), known causes of morbidity and mortality among patients with leukemia and recipients of hematopoietic stem cell transplantations, are described sporadically in patients with lymphoma. We sought to determine the risk factors and outcome of CMV-A and CMV-D among patients with lymphoma. PATIENTS AND METHODS: We conducted a retrospective cohort study with such patients identified between 1997 and 2003 at The University of Texas M. D. Anderson Cancer Center. Seventy-one patients with 82 episodes of CMV-A and/or CMV-D (CMV-A in 38 episodes and CMV-D in 44 episodes) were studied. RESULTS: Cytomegalovirus antigenemia and/or CMV-D were more common among patients with non-Hodgkin's lymphoma than among those with Hodgkin's disease (P = 0.01). Most CMV infectious episodes occurred in patients who had active (88%) and stage III/IV lymphoma (84%). Eleven of 65 patients (17%) with outcome data died with CMV-A and/or CMV-D. Death with CMV infection was more common among patients with CMV-D than among those with CMV-A (29% vs. 3%, respectively, P = 0.005). Predictors of death by univariate analysis included intensive care unit admission, mechanical ventilation, high antigenemia burden, relapse of CMV-A and/or CMV-D, and antiviral-associated toxicity (all P < 0.05). Multivariate analysis identified antiviral toxicity as the only independent predictor of death (P = 0.01). CONCLUSION: In an era of intense and pleiotropic immunosuppressive therapy in patients with lymphoma, CMV-A and CMV-D are significant infections. Preventive strategies might be warranted for patients at risk.

Differential expression profiling of head and neck squamous carcinoma: significance in their phenotypic and biological classification.

The genetic events associated with the development and progression of head and neck squamous carcinoma (HNSC) are largely unknown. We analysed 12 matched pairs of histologically normal squamous mucosa and tumor specimens from six conventional and six phenotypic variants HNSC to define the differentially expressed genes in these tumors. Parallel expression analysis of 8055 unique genes was performed, and the level of the hybridization signal for each gene was measured after normalization. Hierarchical cluster analysis of the expressed genes showed distinct inter- and intra-tumoral patterns in and between conventional squamous carcinoma and squamous carcinoma variants. We also identified 26 (0.32%) differentially expressed genes that were consistently different between matched pairs of normal and tumor specimens; a selected set of the overexpressed genes was validated using real-time quantitative RT-PCR. The majority of the genes were associated with differentiation and proliferation. Our study defines a set of genes that could form the basis for the construction of limited HNSC targeted expression array and in-depth studies and further highlights gene profile differences that may be useful in pathobiologic classification of HNSC.

Gastrointestinal cytomegalovirus disease in patients with cancer: a two decade experience in a tertiary care cancer center.

Although gastrointestinal cytomegalovirus disease (GI-CMVd) is not common in cancer patients, it is associated with high morbidity and mortality. Herein, we review our 2-decade experience with GI-CMVd in such patient population at The University of Texas M.D. Anderson Cancer Center. Forty-seven patients were identified. Thirty-four patients (72%) had an underlying haematological malignancy, and 18 patients (38%) developed GI-CMVd following hematopoietic stem cell transplantation (HSCT). Nine (25%) of the 36 cancer patients with data available had AIDS. Upper-GI tract involvement was more common in patients with haematological malignancies than in those with solid tumours (P=0.02). Patients with AIDS were more likely to have colonic involvement than were those without AIDS (67% vs. 15%, P=0.006), and patients without AIDS were more likely to have gastric involvement (59% vs. 11%, P=0.01). The CMV-attributable mortality rate was 42%. Independent predictors of death by multivariate analysis included disseminated CMV and AIDS (P<0.01). The presentation of GI-CMVd varies according to the type of cancer, and AIDS. GI-CMVd is associated with a high mortality among cancer patients, particularly those with disseminated CMV disease or AIDS.

Gene expression screening of salivary gland neoplasms: molecular markers of potential histogenetic and clinical significance.

Salivary gland neoplasms comprise phenotypically and biologically diverse lesions of uncertain histogenesis. The molecular events associated with their development and clinicopathological heterogeneity remain unknown. To reveal these events, we performed microarray expression analysis using a nylon-filter membrane platform on 18 primary lesions representing the most common benign and malignant types. Our study identified a small set of genes that are differentially altered between normal salivary gland tissues and benign and malignant tumors. Of the 5000 genes arrayed, 136 genes were differentially expressed by normal tissue, benign tumors, and various malignant neoplasms. Hierarchical clustering analysis differentiated between adenoid cystic carcinomas (ACCs) and other malignant subtypes. Non-ACC specimens manifested overlapping patterns of gene expression within and between tumors. Most of the differentially expressed genes share functional similarities with members of the adhesion, proliferation, and signal transduction pathways. Our study identified: 1) a set of genes that differentiate normal tissue from tumor specimens, 2) genes that differentiate pleomorphic adenoma and ACCs from other malignant salivary gland neoplasms, and 3) different patterns of expression between ACCs arising from major and minor salivary gland sites. The differentially expressed genes provide new information on potential genetic events of biological significance in future studies of salivary gland tumorigenesis.

Sarcomatoid carcinoma of the head and neck: molecular evidence for evolution and progression from conventional squamous cell carcinomas.

The underlying events associated with the development of sarcomatoid head and neck squamous carcinoma and the biologic significance remain unknown. To investigate the genetic events involved in the evolution of this entity, comparative analysis of matched microdissected epithelial and sarcoma-like components from 11 primary sarcomatoid carcinomas was performed using microsatellite markers. Nine markers on chromosomes 4p, 9p, and 17p regions (3 per each chromosomal region) were selected based on their informativeness, small product size, and the high alterations in head and neck squamous carcinomas. In this study, loss of heterozygosity (LOH) in at least one marker in either component was noted in all 11 tumors, and instability was found in 10 instances (six in 3 paired specimens and four in the sarcomatoid area only). Concordant results in both components were found in 58 (79.5%) reactions (37 LOH and 21 retention of heterozygosity), and paradoxical findings were noted in 15 instances (20.5%). The latter included LOHs in only two conventional epithelial components and 13 sarcomatoid components. Both keratin-positive and -negative sarcomatoid tumors had a comparable frequency of LOH. The most frequently altered markers in both components were D9S168 and D9S171 (75% each) and D4S1587 (66%). The sarcomatoid components manifested distinctly high alterations at marker D17S520 on chromosome 17p. Our study supports: 1) an evolution of sarcomatoid carcinoma from the conventional epithelial-type, 2) a malignant nature of the sarcomatoid component, and 3) that molecular progression is associated with the sarcomatoid transformation.

Molecular analysis of chromosome 16q regions in dermal analogue tumors of salivary glands: a genetic link to dermal cylindroma?

Dermal analogue tumor, an uncommon subtype of basal cell monomorphic adenoma of the parotid gland, has a remarkable clinical and histologic resemblance to dermal cylindroma. Molecular studies of familial and sporadic cylindromas have shown frequent alterations at chromosome 16q12-13 that have recently been found to house the cylindromatosis gene (CYLD). To determine the involvement of the chromosome 16q12-13 region in dermal analogue tumors, we performed loss of heterozygosity analysis using microsatellite markers flanking the cylindromatosis gene locus in 21 sporadic dermal analogue salivary tumors and 12 salivary and dermal lesions from two sisters. Loss of heterozygosity was identified in 17 (80.9%) of the 21 sporadic tumors and in nine of the 12 dermal and salivary gland dermal analogue tumors from the two sisters; a parathyroid adenoma from one sister and two lymphoepithelial lesions from the second sister showed no microsatellite alterations. Microsatellite instability was only identified in three sporadic tumors at marker D16S308. Markers D16S409 (centromeric), D16S541, and D16S308 (telomeric) to the CYLD gene showed the highest incidence of loss of heterozygosity (>65%). The minimally deleted region was flanked proximally by marker D16S389 and distally by marker D16S419 and spanned the 771.5-megabase fragment that included the CYLD locus. We conclude that dermal analogue tumor and cylindroma share similar incidence of alterations at the 16q12-13 region, supporting a common molecular origin.

Molecular and clinicopathologic comparisons of head and neck squamous carcinoma variants: common and distinctive features of biological significance.

To investigate, for the first time, the events associated with the phenotypic and clinical diversities of head and neck squamous carcinomas (HNSC), we performed molecular analyses on 92 primary tumors representing the entire spectrum of the morphologic subtypes using microsatellite markers at chromosome 3p, 4p, 8p, 9p, 11q, 17p, and 18q regions and correlated the results with the clinicopathologic features and patients' survival. Loss of heterozygosity (LOH) at D9S168 and D9S171 markers on chromosome 9p regions was commonly identified in all subtypes. Distinctive alterations in certain subtypes were noted at chromosomes 3p, 4p, 8p, and 11p regions. In general, less aggressive types (verrucous, papillary, and well-differentiated conventional) had a significantly lower LOH incidence than the more aggressive (basaloid, sarcomatoid, and high-grade conventional squamous carcinoma) categories. Significant association between LOH and age, stage, nodal status, and patient outcome was found. Survival analysis revealed that pathologic categorization (less versus more aggressive) and LOH at marker D11S4167 and D3S2432 are independent predictors of patients' survival. Our analysis also defined a set of limited markers that account for most of alterations within and across these tumor subtypes. Our study indicates that 1) certain genetic markers are common to all subtypes of HNSC supporting their early involvement in tumorigenesis, 2) inter- and intratumoral genetic differences evolve subsequently and may underlie their morphologic heterogeneity, 3) high incidence of LOH in certain regions characterizes aggressive tumors, 4) categorical classification and LOH at 11p and 3p regions independently correlated with patient survival, and 5) a limited set of markers identify the majority of genetic alterations in these tumors.

Differential expressions of cyclin-dependent kinase inhibitors (p27 and p21) and their relation to p53 and Ki-67 in oral squamous tumorigenesis.

The cyclin-dependent kinase inhibitors p27Kip1 and p21WAF1/Cip1 play important roles in cell-cycle regulation. Although alterations of these genes have been linked to tumorigenesis of several human carcinomas, their involvement in head and neck squamous tumorigenesis is rarely investigated. To determine the role of these genes in the evolution of squamous carcinoma of the head and neck we evaluated their protein expression by immunohistochemistry in non-dysplastic squamous epithelium, premalignant lesions and oral squamous carcinomas. The p53 gene and Ki-67 expressions were correlated with traditional clinicopathologic variables. Our study shows that in histologically non-dysplastic squamous epithelium, p27 expression was noted mainly in superficial differentiated cells, whereas p21, p53 and Ki-67 staining was observed in basal and suprabasal cells. In dysplasia, divergent expression between p27 and p21 was observed: p27 precipitously decreased and p21, p53, and Ki-67 increased with histologic progression. In squamous carcinomas, p27 was mainly expressed in well differentiated tumor cell nests, while the expressions of p21, p53, and Ki-67 were variable in the poorly differentiated tumor areas. A significant inverse relationship between p27 expression and those of p21, p53, and Ki-67 was observed, but no significant association between any of these markers and clinicopathologic factors was noted in this cohort. Our study indicates that: i) down-regulation of p27 and up-regulation of p21 are associated with early progression of HNSC, ii) p21 expression correlates positively with proliferation while p27 correlates positively with cell differentiation and iii) concurrent p27 and p21 expression analysis may allow for better assessment of HNSC progression.

Sinonasal adenocarcinoma: evidence for histogenetic divergence of the enteric and nonenteric phenotypes.

Adenocarcinomas of nonsalivary origin represent approximately 10% to 20% of all sinonasal malignancies and are characterized by varying histopathologic features and uncertain histogenesis. To better understand the histogenesis and phenotypic heterogeneity of these tumors, we performed immunohistochemical analyses for cytokeratin (CK) 7 and CK20 on 12 primary sinonasal adenocarcinomas (SNACs) representing the histopathologic spectrum of these tumors, adjacent normal mucosa, and 2 metastatic adenocarcinomas from colonic primaries. The demographic and clinicopathologic characteristics of our cohort were similar to those in previously published series. Our results indicate that histologically normal respiratory-type epithelium and submucosal seromucous glands show restricted reactivity to CK7. Epithelial metaplasia of surface epithelium associated with enteric SNACs was accompanied by a conversion from CK7 positivity to CK20 positivity. All primary enteric-type carcinomas and the 2 colonic metastases were reactive to CK20, but all nonenteric-type tumors were negative for CK20 (P=0.003) and positive for CK7. In some of the enteric types, coexpression of CK7 and CK20 was noted. We conclude that (1) nonenteric-type (seromucinous) adenocarcinoma may originate directly from surface respiratory-type epithelium or from seromucous glands, (2) metaplastic transformation of surface respiratory to enteric-type epithelium precedes the development of enteric adenocarcinoma, and (3) coordinate analyses of CK7 and CK20 reactivity may aid the differential diagnosis of adenocarcinoma in the sinonasal tract.

Differential expression of p53 gene family members p63 and p73 in head and neck squamous tumorigenesis.

p73 and p63 are recently cloned genes that share considerable structural and functional homologies with the p53 tumor suppressor gene. These genes, unlike p53, express multiple mRNA isoforms with variable biologic functions, and their suppressor nature has yet to be confirmed. To determine the interrelationship between these genes in the tumorigenesis of head and neck squamous carcinoma (HNSC), we performed immunohistochemical analyses of their protein products and compared the data with clinicopathologic parameters in 38 patients. In histologically normal epithelium, p53 and p73 showed similar basal and/or parabasal expression, but that of p53 was weaker and discontinuous. p63 staining was noted in more suprabasal cellular layers and was stronger. In dysplasias, all three markers manifested variable but gradual increase in extent and intensity of cellular expression with histologic progression. In carcinomas, p63 was the most frequently expressed (94.7%), followed by p73 (68.4%) and p53 (52.6%). Significant statistical correlation was noted only between p63 and p73 expressions (P =.04). Although no statistical correlation was found between p53 and p63 or p73, p53-negative tumors overexpressed either p63 or p73. p73 expression was associated with distant metastasis and perineural/vascular invasion. Our study indicates that (1) p63 and p73 expression may represent an early event in HNSC tumorigenesis, (2) the lack of correlation between p73 or p63 and p53 expression suggests an independent and/or compensatory functional role, (3) p73 expression may play a part in HNSC progression, and (4) p73 and p63 may function as oncogenes in the development of these tumors.