Hanna Strømme Koppang

DNA CONTENT AS A PROGNOSTIC MARKER IN PATIENTS WITH ORAL LEUKOPLAKIA

BACKGROUND Oral leukoplakia may develop into squamous-cell carcinoma, which has a poor prognosis. Risk factors for oral carcinoma have been identified, but there are no reliable predictors of the outcome in individual patients with oral leukoplakia. METHODS We identified 150 patients with oral leukoplakia that was classified as epithelial dysplasia and measured the nuclear DNA content (ploidy) of the lesions to determine whether DNA ploidy could be used to predict the clinical outcome. Biopsy specimens obtained at annual follow-up visits were graded histologically and classified with respect to DNA content in a blinded fashion. Disease-free survival was assessed in relation to DNA ploidy and the histologic grade. The mean duration of follow-up was 103 months (range, 4 to 165). RESULTS Among 150 patients with verified epithelial dysplasia, a carcinoma developed in 36 (24 percent). Of the 150 patients, 105 (70 percent) had diploid (normal) lesions, 20 (13 percent) had tetraploid (intermediate) lesions, and 25 (17 percent) had aneuploid (abnormal) lesions at the time of the initial diagnosis. A carcinoma developed in 3 of the 105 patients with diploid lesions (3 percent), as compared with 21 of the 25 patients with aneuploid lesions (84 percent), yielding a negative predictive value of 97 percent with respect to the diploid lesions and a positive predictive value of 84 percent with respect to the aneuploid lesions. Carcinoma developed in 12 of 20 patients with tetraploid lesions (60 percent). The mean time from the initial assessment of the DNA content to the development of a carcinoma was 35 months (range, 4 to 57) in the group with aneuploid lesions and 49 months (range, 8 to 78) in the group with tetraploid lesions (P=0.02). The cumulative disease-free survival rate was 97 percent among the group with diploid lesions, 40 percent among the group with tetraploid lesions, and 16 percent among the group with aneuploid lesions (P<0.001). CONCLUSIONS The DNA content in cells of oral leukoplakia can be used to predict the risk of oral carcinoma.

Cyclooxygenase-2 (COX-2) expression in high-risk premalignant oral lesions.

Emerging data indicate a link between genetic instability and up-regulation of cyclooxygenase-2 (COX-2). To see if individuals at high risk of oral cancer are candidates for treatment with selective COX-2 inhibitors (coxibs), levels of COX-2 expression in healthy, premalignant and cancerous oral mucosa were compared with the occurrence of DNA ploidy status as a genetic risk marker of oral cancer. COX-2 gene product was evaluated immunohistochemically in 30 healthy persons, in 22 patients with dysplastic lesions without previous or concomitant carcinomas, and in 29 patients with oral carcinomas. The immunohistochemical findings were verified by western blotting. COX-2 expression was correlated to DNA content as a genetic risk marker of oral cancer. COX-2 was up-regulated from healthy to premalignant to cancerous oral mucosa. Thus, COX-2 expression was found in 1 case of healthy oral mucosa (3%). All specimens from healthy mucosa had a normal DNA content. In patients with premalignancies. In 29 patients with oral carcinomas, cyclooxygenase-2 expression was observed in 26 (88%), and aneuploidy was observed in 25 cases (94%, P=0.04). Notably, of 22 patients with dysplastic lesions, COX-2 was exclusively expressed in a subgroup of nine patients (41%) identified to be at high risk of cancer by the aberrant DNA content of their lesions. Seven of these patients were followed for 5 years or more. An oral carcinoma developed in six of them (85%; P=0.02). These findings emphasize the need to determine whether coxibs can reduce the risk of oral cancer in patients with high-risk precancerous lesions.

Gross Genomic Aberrations in Precancers: Clinical Implications of a Long-Term Follow-Up Study in Oral Erythroplakias

PURPOSE Gross genomic aberrations are increasingly seen as a cause rather than a consequence of carcinogenesis. Carcinomas may be prevented by systemically acting agents when used in high-risk individuals. If gross genomic aberrations could be shown to be predictive markers in precancers, they could serve as a tool for identifying high-risk individuals to be included in chemopreventive trials. PATIENTS AND METHODS To investigate the predictive power of gross genomic aberrations in several types of oral premalignancies, we analyzed 57 biopsies from oral erythroplakias of 37 patients, both histologically and for DNA content. DNA content was measured by high-resolution image cytometry, and distribution histograms of DNA content were generated and interpreted according to established protocols. The primary end point was cancer-free survival. RESULTS Fifty-seven dysplastic oral red lesions from 37 patients were investigated. Forty-one lesions from 25 patients were classified with aberrant DNA content (DNA aneuploidy), of which 23 patients (92%) later developed an oral carcinoma (after a median observation time of 53 months; range, 29 to 79 months). Of 12 patients having altogether 16 lesions with normal DNA content, none developed a carcinoma (median observation time, 98 months; range, 23 to 163 months; P <.001). In multivariate analysis, DNA content was a significant prognostic factor (P <.001), whereas histologic grade, sex, use of tobacco, size and location of lesions, and the presence multiple of lesions were not. CONCLUSION Gross genomic aberrations are highly predictive for the subsequent occurrence of carcinomas from a wide range of oral premalignancies.

Cellulose fibers from endodontic paper points as an etiological factor in postendodontic periapical granulomas and cysts

Histological sections of eight periapical granulomas and cysts developing after conventional endodontic therapy and displaying faintly hematoxylinophilic, birefringent foreign bodies were investigated by light and polarization microscopy, scanning electron microscopy, energy-dispersive X-ray, and chemical analysis. In addition to a variably dense mononuclear infiltrate, the granulomas and cysts revealed varying amounts of giant cells associated with the birefringent foreign bodies. These structures were identified as cellulose fibers, most probably originating from endodontic paper points, which in our opinion can be held responsible for the initiation and perpetuation of chronic postendodontic periapical lesions.

Malignant transformation in oral lichen planus

A carcinoma arose in the buccal mucosa of a 71-year-old woman suffering from several systemic diseases, and on extensive medication. The buccal mucosa had been affected by oral lichen planus for more than 9 years. The possibility of malignant transformation of oral lichen planus is discussed.

Nerve growth factor receptor (p75NTR) and pattern of invasion predict poor prognosis in oral squamous cell carcinoma

Aims:  To evaluate the expression of p75 neurotrophin receptor (p75NTR) in oral squamous cell carcinoma (OSCC). The results were related to tumour node metastasis (TNM) stage, World Health Organization (WHO) grade, invasive front grading (IFG) and prognosis.

Human papillomavirus type 13 and focal epithelial hyperplasia of the oral mucosa: DNA hybridization on paraffin-embedded specimens

16 cases of focal epithelial hyperplasia (Hecks disease) were studied for the presence of human papillomavirus DNA by means of nucleic acid hybridization. Hybridization was carried out in situ with biotin-labelled probes of HPV 1, 6, 11, 13, 16, and 18 DNA under stringent and non-stringent conditions. Under non-stringent conditions, 6 of 16 cases (38%) hybridized to a mixture of HPV 1, 6, 11, 16, and 18 DNA. When these probes were applied under stringent conditions, only one case could be shown to be weakly positive for HPV 6/11 DNA. Further stringent hybridizations, which were conducted with a HPV 13 probe on 12 of our 16 cases, revealed a positive result in 9 of 12 cases (75%). The results of our study strongly substantiate the concept that HPV 13 or a closely related HPV type is associated with lesions morphologically presenting as focal epithelial hyperplasia.

Oral verrucous carcinoma

Verrucous carcinoma is a well-defined variant of the squamous cell carcinoma. Although it is reported to be rare in the Scandinavian countries, 16 cases have been diagnosed in the Southern part of Norway from 1975 to 1982. The clinical and histological characteristics were investigated. The most common site of occurrence was the mandibular alveolar ridge. The average age was 71 years, and unlike most other series of verrucous carcinoma, there was a female predominance and use of tobacco seemed to be the exception. The patients mainly complained of ill-fitting dentures. Adequate surgical excision appears to be the treatment of choice.

Grading of nuclear pleomorphism in oral carcinomas. Higher prognostic value than stereological assessment of nuclear volume

A more objective and reproducible grading system is needed in order to give better prognostic indicators and thereby offer improved treatment to oral cancer patients. Recently, simple objective stereological techniques for cellular estimates have emerged, of which the estimate of mean nuclear volume has shown a correlation with prognosis for various cancers. We have therefore measured the mean nuclear volume in 44 invasive buccal mucosal squamous cell carcinomas and related it to the survival of patients. The mean nuclear volume did not correlate with prognosis for these patients (p = 0.25). However, the nuclear polymorphism, which is subjective even though it is based on well‐described criteria in a histopathological grading system, correlated significantly with prognosis (p = 0.03). These findings indicate that the traditional histopathological evaluation of nuclear polymorphism includes valuable prognostic information.

Sarcoidosis with mandibular involvement: Report of a case

A case of mandibular involvement in sarcoidosis is presented. The diagnosis was based on positive chest roentgenograms, involvement of superficial and mediastinal lymph nodes of epithelioid tubercles, negative tuberculin test, and negative results of an examination with respect to tubercle bacilli. Mandibular involvement was diagnosed tentatively roentgenographically and verified by histopathologic examination. The mandibular lesion was treated surgically, and the defect healed uneventfully after less than 1 year. Almost complete normalization of the pulmonary lesions had taken place after 2 years.