Faculty Bibliography

Beta-6 Integrin, tenascin-C, and MMP-1 (matrix metalloproteinase-1) are invasion-related proteins that are frequently overexpressed in many human malignancies. The objective of this study was to determine whether there is overexpression of these molecules in three types of salivary neoplasms showing markedly different behavior. A total of 55 formalin-fixed, paraffin-embedded archived specimens comprising 19 adenoid cystic carcinomas (ACC), 18 polymorphous low-grade adenocarcinomas (PLGA) and 18 pleomorphic adenomas (PA) were utilized in this study. A standard immunohistochemical technique was used to determine the expression levels of beta-6 integrin, tenascin-C, and matrix metalloproteinase-1 (MMP-1) proteins. Sections were assessed semiquantitatively, and tumors were divided into two groups, low-expressors (0-1+) and high-expressors (2-3+) for statistical analysis. Staining was graded as 0 (<1% positive tumor cells), 1+ (<25% positive tumor cells), 2+ (25-50% positive tumor cells), and 3+ (>50% positive cells). The results showed that the malignant tumors were higher expressors of beta-6 than the benign tumors. ACCs showed significantly higher expression of beta-6 than PAs (p=0.04). No significant difference was observed between ACCs and PLGAs. beta-6 expression was rarely seen in normal salivary gland epithelium and was occasionally present in mucosa overlying the tumors. PAs were high-expressors of tenascin-C with a significant difference relative to ACCs (p=0.03). A majority of tumors in all three tumor types showed high expression of MMP1 with expression significantly greater in the PAs compared to ACCs (p=0.008). We conclude that ACCs and PLGAs express beta-6, tenascin-C, and MMP-1, but that their expression patterns are not significantly different. beta-6 appears to be more closely associated with the malignant tumors, and MMP-1 more closely associated with the benign tumors. We believe that beta-6, tenascin-C, and MMP-1 proteins are part of the molecular repertoire used by salivary tumors for malignant invasion and benign tumor expansion

In this study we have developed and tested a novel pain questionnaire to measure the pain experienced by patients with oral squamous cell carcinoma. The questionnaire consisted of 8 questions rated by the patient on a visual analog scale. Patients completed the questionnaire at the time of initial presentation before surgical treatment. None of the patients were taking analgesics. The responses were then scored and compiled with patient data and pathology reports. Of the 15 completed questionnaires, 14 patients reported some level of functional restriction from pain (mean, 46.6 +/- 25.2, scale of 0 to 100 mm). On average, patients experienced significantly higher function-related, rather than spontaneous, pain intensity and sharpness. Men (n = 8) had a significantly higher level of function-related pain intensity and sharpness than women had (n = 7). There was a strong correlation between nodal disease and increased levels of spontaneous intensity, sharpness, throbbing, and overall functional restriction. PERSPECTIVE: The results of this study indicate the heterogeneous nature and function dependence of oral cancer pain. The questionnaire we have developed in this study will allow for correlations between pain parameters and specific tumor biology in future studies

PURPOSE: Although an important risk factor for oral cancer is the presence of epithelial dysplasia, many lesions will not progress to malignancy. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases capable of digesting various structural components of the extracellular matrix. Because MMPs are frequently overexpressed in oral squamous cell carcinoma (SCC), we hypothesized that they are also overexpressed in oral dysplasias; we also hypothesized that those dysplasias that progress to oral cancer express higher levels of MMPs than those lesions that do not progress. EXPERIMENTAL DESIGN: In this retrospective study, we examined changes in MMP-1, -2, and -9 mRNA expression using quantitative TaqMan reverse transcription-polymerase chain reaction in 34 routinely processed oral dysplasias and 15 SCCs obtained from 34 patients. After several years of close follow-up, 19 dysplasias progressed to oral SCC and 15 did not. RESULTS: Overall, MMP-1 mRNA was overexpressed (>2-fold) in 24 of 34 (71%) dysplasias and 13 of 15 (87%) oral SCCs. MMP-2 overexpression was seen in 11 of 34 (32%) dysplasias and 7 of 15 (47%) cancers; for MMP-9, overexpression was identified in 29 of 34 (85%) dysplasias and 15 of 15 (100%) cancers. MMP-1 and -9 levels were significantly higher in the SCCs compared with all oral dysplasias (P = 0.004 and P = 0.01, respectively). MMP-1 and -9 mRNA levels were significantly higher in the oral dysplasias that progressed to oral cancer compared with those that did not (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: Levels of MMP-1 and -9 mRNA may be markers of malignant transformation of oral dysplasia to oral cancer

PURPOSE: The study goal was to evaluate neurosensory changes after liquid nitrogen cryotherapy in the management of mandibular lesions in close proximity to the inferior alveolar nerve. PATIENTS AND METHODS: The design of the study was a retrospective review. Sixteen patients with posterior mandibular lesions (15 odontogenic keratocysts and 1 fibromyxoma) in close proximity to the inferior alveolar nerve were treated with a standardized enucleation and cryotherapy technique. Postoperative evaluation included patients report of symptoms and formal neurosensory testing. RESULTS: All patients had altered sensation in the distribution of the inferior alveolar nerve immediately after cryotherapy. Two patients experienced anesthesia, and the remaining 14 patients showed paresthesia. The average time for return or improvement in sensation was 91 days (range, 6 to 235 days). The average time of follow-up was 2.6 years (range, 0.5 to 7.3 years). At the time of last follow-up, no patients had anesthesia or dysesthesia. Four patients had full return of sensation and 12 patients had paresthesia. No patients reported significant difficulty from abnormal nerve function. All 16 patients experienced some return of sensation; 9 patients had full or near full return of sensation. CONCLUSIONS: Based on these results, the combination of enucleation and liquid nitrogen cryotherapy produces minimal alteration of inferior alveolar nerve function

PURPOSE: The association between tobacco smoking and oral squamous cell carcinoma is well established. However, few studies have evaluated the smoking history based on a smoking versus never-smoking history or analyzed the relationship between smoking history and site and stage of presentation. The purpose of this study was to examine the relationship between smoking versus never-smoking history and the stage and site of presentation of oral squamous cell carcinoma. PATIENTS AND METHODS: The design of this study was a retrospective review of all patients presented at the Legacy Emanuel Hospital Head and Neck Tumor Board in Portland, Oregon, with a biopsy-proven oral squamous cell carcinoma between 1998 and 2000. Data collected included age, gender, smoking history (smoker versus never smoker), pack-years of tobacco, site, and stage (T, N, and group stage) at presentation. RESULTS: A total of 67 patients were reviewed; 33% of patients were never smokers and 67% of patients had a history of smoking with an average of 49.4 pack-years. The floor of mouth and gingiva were the most commonly affected sites. There was a statistically significant difference between site of presentation and a history of smoking (P =.0007). The 2 sites that showed a significant association with smoking were posterolateral tongue and floor of mouth. CONCLUSIONS: The findings of this study demonstrate that approximately one third of patients with oral squamous cell carcinoma will report that they have never smoked. There was a strong association between a history of smoking and carcinoma involving the posterolateral tongue and floor of mouth

PURPOSE: Maxillary reconstruction after maxillectomy remains a great challenge for the reconstructive oral and maxillofacial surgeon. This article is a clinical retrospective analysis of patients reconstructed with zygomaticus implants after maxillary ablation. PATIENTS AND METHODS: The design of the study was a retrospective review of 9 patients requiring near-total or total maxillectomy for pathologic reasons. Clinical records, photographs, and radiographs were studied. Financial billing statements were reviewed to determine charges for implant reconstruction and method of payment. RESULTS: Maxillary reconstruction using zygomaticus and standard endosseous implants was performed in 9 patients. Maxillary resection was performed for the following reasons: salivary gland malignancy (n = 2), squamous cell carcinoma (n = 5), maxillary mucormycosis (n = 1), and extensive maxillary atrophy and infection secondary to subperiosteal maxillary implant placement (n = 1). A total of 28 zygomaticus implants and 10 standard endosseous implants were used to reconstruct the 9 patients. Six zygomaticus implants and 3 standard endosseous implants failed. The time of zygomaticus implant placement ranged from placement at the time of resection to 3.2 years after the resection. Five patients received radiation therapy. Five patients have been reconstructed with a maxillary obturator and have been functioning with the prosthesis for a minimum of 2 years. CONCLUSION: The combination of zygomaticus and standard endosseous implants can be used to reliably reconstruct patients after extensive resection of the maxilla

The nasolabial flap is a straightforward and time-tested reconstructive option suitable for a variety of facial and oral defects. The superiorly and inferiorly based variants are well described in the literature and offer a rapid and reliable alternative to time-consuming microvascular free flaps and less esthetic skin grafts. Despite newer and more complex alternatives, the nasolabial flap maintains its prominent position in the reconstructive armamentarium of the oral and maxillofacial surgeon