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The underlying molecular abnormalities associated with head and neck squamous cell carcinoma in young adults (< 40 years) are unknown. We analyzed DNA extracted from paired microdissected samples of normal squamous epithelia and invasive oral squamous cell carcinomas from 36 young adults at microsatellite loci commonly found in older patients and correlated the results with clinicopathologic parameters and outcome. Our results showed that 30 of the 36 (83%) tumors manifest loss of heterozygosity (LOH) in at least one marker. Microsatellite instability was manifested in only six tumors (< 17%). The highest incidences of alterations were noted at markers D9S168 (9p23-22), TP53 (17p13), and D17S799 (17p11) on the short arms of chromosomes 9 and 17. In general, the incidences of LOH at 3, 9 and 17p regions in young adults were similar to those found in older patients. No correlation between LOH at chromosomes 3, 9, and 17p and clinicopathologic parameters was found. Our study indicates that chromosomal regions with frequent genetic alterations involved in young adult squamous tumorigenesis are similar to those reported in older patients. Further studies of other chromosomes in this population are underway to define the novel molecular features of these tumors.

Background: The clinical course of laryngeal squamous cell carcinoma (LSCC) varies considerably among patients. New biologic markers are needed to facilitate the stratification of individual patients within the conventional clinicopathologic stages of LSCC., Methods: Eighty-three LSCCs from an equal number of patients who received at least 10 years of follow-up were investigated for p53, p21WAF1/CIP1, and bcl-2 protein expression by immunohistochemical techniques. The results were correlated with various clinicopathologic parameters, DNA content, and patient outcome by univariate and multivariate statistical analyses., Results: Stage IV disease, large tumor size (>3 cm), positive lymph node status, extranodal extension, and p53 overexpression (in > 75% of cells) correlated significantly with prognosis in univariate analysis. There was no correlation between patient outcome and age, gender, race, histologic differentiation, or expression of bcl-2 or p21WAF1/CIP1. In multivariate analysis, lymph node status and p53 overexpression were the only factors significantly associated with survival., Conclusions: High p53 expression and positive lymph node status were independent predictors of the outcomes of patients with LSCC. These factors may assist in prognostication and better classification of patients for treatment.

Background: Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). Detection of EBV in biopsy specimens may serve as a tumor marker., Methods: To assess the sensitivity and specificity of the polymerase chain reaction (PCR) and in situ hybridization in the diagnosis of NPC, formalin fixed, paraffin embedded nasopharyngeal biopsies from patients in Taiwan suspected of having NPC were studied., Results: In specimens from 107 patients with NPC, EBV was detected by PCR in 97 cases (90.7%) and by EBER in situ hybridization in 105 cases (98.1%). In specimens from 61 patients without neoplasia, EBV was detected by PCR in 7 cases (11.5%) and by EBER in situ hybridization in 0 cases., Conclusions: These results suggest that although EBV DNA may occasionally be detected in nonneoplastic nasopharyngeal tissues, cells expressing EBER are not. EBER in situ hybridization may therefore prove to be a useful adjunct in the diagnosis of NPC.

Chronic suppurative otitis media, averaging 20 or more years of duration, has been associated with cancer in this region in 40%-80% of cases. Although human papillomaviruses (HPV) have been implicated in many human squamous-cell neoplasms, their role in the pathogenesis of middle-ear malignancies remains unexplored. In this study, we investigated the presence and subtypes of HPV in middle-ear carcinomas. Formalin-fixed and paraffin-embedded tumor tissues were sampled for DNA extraction. PCR was done with consensus primers, capable of detecting HPV 16, 18, 31, 33, 52b and 58. Typing of the products generated by consensus primers was performed with restriction enzyme digestion. It was found that a resulting 89% (8/9) of the middle-ear carcinomas contained HPV DNA. Coexistence of HPV 16 and 18 was detected in 3 squamous-cell carcinomas. HPV 16 was detected in 4 squamous-cell carcinomas and 1 adenocarcinoma. The high prevalence of high-risk-type HPV in carcinomas of the middle ear suggests that viral infection may be an important etiologic component in the carcinogenic process.

Squamous cell carcinoma of the middle ear (MESCC) is an uncommon tumor and is associated with a history of long-term chronic otitis media (COM) in most cases. Although the human papillomaviruses (HPVs) have been implicated in many human neoplasms, its role in the pathogenesis of MESCC has not been studied. Polymerase chain reaction (PCR) using consensus primers for the detection of HPV types 6, 11, 16, 18, 31, 33, 52b, and 58 was applied in screening fourteen cases of MESCC from archival material. Further subtyping was performed by restriction enzyme digestion of PCR products and by in situ hybridization method on tissue sections. Of the fourteen cases of MESCC, eleven were found to have HPV DNA. HPV-16 was detected in all positive cases. Five cases revealed both HPV-16 and -18. A history of long-term COM (> 3 years) was found in thirteen of the cases. This is the first report to localize HPV-16/18 in MESCC on both the tissue level and the molecular level. The high prevalence of HPV in COM-associated MESCC therefore provides a good model to explain the pathogenesis of chronic-inflammation-related human malignancies.

Sixty squamous cell carcinomas of tongue and buccal mucosa were examined for expression of p53 protein by using an immunohistochemical technique improved by an antigen retrieval method. Twenty-seven (45%) tumors demonstrated strongly positive staining. Thirteen of p53-positive tumors (48%) also exhibited overexpression of p53 in immediately adjoining hyperplastic or pre-malignant epithelium. All 22 metastatic lymph nodes and 18 local recurrent lesions (except two) had an identical p53 immunophenotype to their corresponding primary sites. Mitotic indices were significantly higher in p53-positive tumors (P < 0.01); however, no association of PCNA scores with p53 expression was found (P > 0.1). There was no correlation between p53 overexpression and tumor grade, size and staging, vascular invasion, lymph node metastasis, and early local recurrence. Overexpression of p53 was found to be relatively higher, although not statistically significant, in nonsmokers than in heavy smokers (66.7% vs. 42.9%), and in nonbetel-quid chewers than in heavy chewers (62.5% vs. 34.2%). These data are consistent with the hypothesis that inactivation of p53 protein may occur in the early phases of oral tumorigenesis. It may not be a useful prognostic marker but could possibly be used for risk assessment and surveillance of local recurrence.

Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S phase of the cell cycle which can be detected immunohistochemically in paraffin-embedded tissue as a useful marker for the proliferating fraction of cells in tissue specimens. Thirty-eight cases of oral squamous cell carcinoma were studied in groups according to clinical staging and histological grading (UICC system), these included 5 cases of T1, 13 cases of T2, and 20 cases of T3, and 19 cases of G1, 12 cases of G2, and 7 cases of G3. The mean percentage of PCNA positively stained tumor cells in this series was 29.2. The mean percentages of PCNA-positive cells in each stage and grade were: T1 (13.7%), T2 (24.4%), and T3 (34.3%); G1 (30.5%), G2 (24.8%), and G3 (33.2%). The results indicate that the percentage of PCNA positively stained tumor cells in oral squamous cell carcinoma was significantly greater when tumor size was larger than 2 cm (T1 versus T2/T3). However, there was no significant difference between T2 and T3. There was no correlation between the number of PCNA-stained tumor cells and histological grade.

The distribution pattern of certain monosaccharides in the epithelial cells of the hamster buccal pouch was studied during carcinoma development induced by 9,10-dimethyl-1,2-benzathrancene (DMBA). An avidin-biotin-peroxidase complex (ABC) immunohistochemical technique with high affinity biotinylated lectins was employed to identify monosaccharides. Lectins used in this experiment included Concanavalin A (Con A), for identifying mannose or glucose, Ricinus communis agglutinin I(RCA-I), for identifying galactose, and Ulex europaeus agglutinin I(UEA-I), for identifying fucose. The results show that in normal buccal pouch epithelial cells, fuctose or galactose were concentrated predominantly on the cellular membrane, while mannose and glucose were distributed in the cytoplasm. In the epithelial cells undergoing neoplastic transformation induced by DMBA, most cells showed decreased staining of the above-mentioned monosaccharides, while in other areas the cells were heavily stained. However, the most striking change which occurred was that galactose and fucose shifted from the cellular membrane to the intracytoplasmic area during the malignant transformation. Thus, the changes of anatomic location and intensity of staining of monosaccharides in the buccal pouch epithelium may be used as a criteria for early histochemical diagnosis of malignant transformation.