Nucleolar organizer regions in meningiomas

Paraffin sections of 305 meningeal tumours were analysed for the presence of nucleolar organizer region (Ag-NOR) in the neoplastic cells, using a one step silver-colloidal staining method. The mean (+/- SEM) Ag-NOR counts were 2.73 +/- 0.21 for atypical and 2.91 +/- 0.18 for papillary variants of meningioma. In meningotheliomatous and transitional variants of meningioma, the mean Ag-NOR counts were 1.41 +/- 0.34 and 1.38 +/- 0.31, respectively. The recurrence rates were significantly higher in atypical meningiomas than in other histopathological variants (p < 0.05). Differences in the mean Ag-NOR numbers between meningothelial and transitional variants in their primary and recurrent tumours were not significantly different (p > 0.05). The results of this study indicates that estimation of Ag-NORs can be applied in predicting the aggressive clinical behaviour of primary meningeal tumours.     

Nucleolar organizer regions in conjunctival nevi and melanomata

The objective of this study was to compare the argyrophil nucleolar organizer region (Ag-NOR) counts of conjunctival nevi and melanomata and to compare the efficacy of this method in their differential diagnosis. Nine histologically diagnosed conjunctival nevi and three conjunctival malignant melanomas were studied. Representative sections were stained using the AgNOR technique. Fifty cells of each melanocytic lesion were randomly selected without knowing their histologic diagnosis. The AgNORs were visualized at a magnification of x1000. They consisted of clusters >1 micron in diameter and of satellites <1 micron in diameter, which were counted and recorded for each cell separately. The mean AgNOR count for the nevi was 1.12 clusters and 1.72 satellites per cell, while the count for the melanomas was 1.6 clusters and 6.8 satellites per cell. These results are statistically significant. There was no overlap between the number of AgNOR clusters and satellites in conjunctival nevi and melanomas, indicating that the AgNOR count might be a useful tool in distinguishing benign from malignant conjunctival melanocytic lesions.     

Nucleolar organizer regions in lymphomas: a quantitative study

Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NORs) have been studied in paraffin sections of 76 non-Hodgkin's lymphomas, five normal lymph nodes, and five lymph nodes. The mean number of nucleolar organizer regions per nucleus was 1.19 (SD:0.09) for normal lymphocytes, 3.04 (SD:0.14) for reactive lymph nodes, 2.79 (SD:0.44) for low-grade lymphomas, 6.33 (SD:1.58) for intermediate-grade lymphomas, and 10.53 (SD:1.97) for high-grade lymphomas. There were highly significant differences in Ag-NOR counts among the groups (p < 0.001). The Ag-NOR regions were often observed in nuclei in areas where nucleoli themselves were invisible. It is suggested that this method is useful in diagnostic histopathology and in differentiation of the grade of lymphomas.     

Argyrophilic nucleolar organizer regions staining is useful in predicting recurrence-free interval in oral tongue and floor of mouth squamous cell carcinoma

BACKGROUND: Argyrophilic nucleolar organizer regions (AgNORs) represent a tissue marker of cell proliferative activity. The purpose of this study was to assess the prognostic value of AgNORs expression in oral squamous cell carcinoma (SCC). METHODS: The AgNORs area/nucleus was studied in paraffin sections by means of digital image analysis in 43 cases of stage II oral tongue and floor of the mouth SCC. RESULTS: Time free of disease was considered a dependent variable of a binary indicator of AgNORs expression (7.77 microns2/nucleus as a cut-off point). High AgNORs level was associated with a statistically significant negative effect on recurrence-free interval of disease in a Cox proportional hazards models controlled for occult lymph node metastasis, involvement of the surgical margins, thickness of the lesion, and vascular invasion. CONCLUSIONS: The AgNORs area increased the capability of predicting which patients have a high risk of recurrence of cancer, and its evaluation may provide useful information for the therapeutic approach to the oral tongue and floor of the mouth SCC.     

Treatment policy for maxillary sinus carcinoma

Some 908 cases of malignant tumors of the nose and paranasal sinuses treated from 1957 through 1974 were statistically analysed. The most common tumor site was the maxillary sinus (91.4%) and the most common histological figure was carcinoma (92.4%). The crude and relative survival rates for each treatment mode were calculated in January 1975. The number of cases and the 5 year relative survival rates of the main groups were as follows: I. Primary cases of malignant tumors (761 cases) 29.2% A. Carcinoma (709 cases) 29.3% B. Sarcoma (45 cases) 27.4% II. Primary cases of maxillary sinus carcinoma (561 cases) 26.1% A. Period 1957-66 (282 cases) 22.8% 1. Combination of irradiation and surgery (114 cases) 36.9% 2. Irradiation alone (168 cases) 12.7% B. Period 1967-69 (130 cases) 34.5% 1. Irradiation with 5-FU intra-arterial infusion (25 cases) 36.1% 2. Irradiation with intra-arterial infusion of other radiosensitizers (35 cases) 35.7% 3. Irradiation only without infusion (45 cases) 35.2% C. Period 1970-71, Linac X-ray irradiation (61 cases) 15.9% D. Period 1972-73, Irradiation with 5-FU infusion (80 cases), 3 year relative survival rate 39.3% The stage-grouping of maxillary sinus carcinoma based on the classification of tumor spread in the TNM system was recommended for the comparison of survival rates. The best mode of treatment in our experience is the combination of Co-60 gamma-ray irradiation and continuous intrarterial infusion of 5-FU. A curettage during irradiation is recommended. A maxillectomy should be performed only for irradiation failure cases.     

Gallium-67 scanning in the differentiation of maxillary sinus carcinoma from chronic maxillary sinusitis

Gallium-67 scans of 25 patients in whom the clinical symptoms and radiographic findings were suggestive of either maxillary sinus carcinoma or chronic sinusitis proved to be valuable in the differentiation between the two disease processes. Those patients with carcinoma had positive scans, while those with sinusitis had either negative or only weakly positive scans.     

Distinct P-cadherin expression in cultured normal human keratinocytes and squamous cell carcinoma cell lines

A thermal threshold measurer (TTM) apparatus was developed and tested in 12 dry, nonpregnant, culled cows with the purpose of measuring the thermal nociceptive threshold and of finding the response to morphine sulphate dosages. The cows received a cumulative dose (from 0.00 to 0.40 mg/kg BW) of morphine sulphate through a catheter in the jugular vein. The interval between doses was 20 min, and a nociceptive test was performed 15 min after each injection. The TTM device consisted of a 60 W halogen bulb mounted in a 15 cm PVC tube, with a 0.6 s response time probe attached to its end, connected to a thermocouple. The probe measured the response temperature on the skin over the middle phalanges on the dorsum of the forefoot. The radiating heat stimulus from the bulb was instantaneously terminated with the foot-lift response of the tested animal. The nociceptive response to the 0.00 mg/kg dose was considered the baseline and subsequent measurements were expressed in difference from it. Data were evaluated in a regression analysis using the GLM procedure. A significant elevation (P < 0.0001) in the nociceptive threshold of the cows with cumulative dosing of morphine sulphate was noticed. A high variability (P < 0.0001) in the response among animals was also detected, suggesting that a 2-step dose of morphine sulphate is necessary to achieve a certain degree of induced analgesia in all cows. The nociceptive assay described, using the TTM device, was able to detect an elevation of the thermal threshold of cows due to morphine sulphate induced analgesia. An increase in locomotory behaviour or other side effects due to morphine sulphate were not noticed.     

Subungual squamous cell carcinoma in Darier''s disease

Complete coronary revascularization using arterial grafts has been performed recently because of their improved patency rates. However, as the need to repeat coronary bypass surgery has become more frequent, it can be difficult to find adequate conduits for further bypass surgery. Therefore, we investigated the use of the left thoracodorsal artery (LTDA) as an alternative bypass conduit. The length from its origin, internal diameter, and number and location of branches were angiographically measured in 16 patients, and in situ blood flow volume and external diameter were intraoperatively measured in 8. Moreover, each specimen of the LTDA, the internal thoracic artery (ITA), and the inferior epigastric artery (IEA) were evaluated histologically. We found that the thoracodorsal artery has the same diameter as the ITA angiographically, and the same histological findings as the IEA. In conclusion, the thoracodorsal artery may be useful as a coronary arterial graft.     

Detection of human papillomavirus DNA in laryngeal squamous cell carcinoma by polymerase chain reaction

Although human papillomaviruses (HPVs) have been found in many, but not all, tumours of the oral cavity, nose, pharynx and larynx, the true role of HPV in malignant tumours of the head and neck is still unclear. The presence of HPV DNA was investigated in 45 fresh squamous cell carcinoma (SCC) specimens and in 29 normal mucosa specimens collected from 45 primary laryngeal SCC patients. HPV DNA was detected using the polymerase chain reaction (PCR) with consensus primers that detect HPV types 6, 11, 16 and 18.9 of the 45 patients (20%) were HPV positive; the presence of HPV was also detected in the corresponding normal laryngeal mucosa of four of the 29 specimens (14%). No statistically significant differences were found between the presence of HPV DNA in normal specimens and in neoplastic mucosa specimens. No correlation was found between HPV DNA positive tumours and size, T classification, lymph node involvement and histological grading. This study adds further evidence suggesting a possible role of HPV DNA infection in laryngeal carcinogenesis.     

Nitric oxide synthase activity in human squamous cell carcinoma of the head and neck

A continuous fluorometric assay for tryptophan hydroxylase activity based on the different spectral characteristics of tryptophan and 5-hydroxytryptophan is presented. Hydroxylation of tryptophan at the 5-position results in a large increase in the fluorescence of the molecule. The assay selectively monitors the fluorescence yield of 5-hydroxytryptophan by exciting the reaction mix at 300 nm. The rate of increase of the emission signal was found to be directly proportional to the enzyme concentration. Inner filter effects due to quinonoid dihydropterin accumulation were eliminated by the inclusion of a thiol reductant. Activity measured using this assay method was found to be the same as that determined by established discontinuous HPLC assay methods. The application of the assay to routine activity measurements and to steady-state determinations with the substrates tryptophan and tetrahydropterin is described.     

Human squamous carcinoma cell invasion in organ-cultured skin

A chronic, loose constriction of the sciatic nerve in rat produces behavioral signs of spontaneous pain and cutaneous hyperalgesia (Bennett and Xie, Pain, 33 (1988) 87-107) as well as an abnormal spontaneous activity and adrenergic sensitivity of certain dorsal root ganglion (DRG) cells with axons in the injured nerve (Kajander et al., Neurosci. Lett., 138 (1992) 225-228; Xie et al., J. Neurophysiol., 73 (1995)1811-1820). The present study investigated whether the spontaneous activity and adrenergic sensitivity were intrinsic properties of injured DRG cells and manifested in vitro, i.e., not dependent on intact blood circulation and an intact, functioning sympathetic nervous system. Two weeks after a loose constriction of the sciatic nerve, the L4 or L5 DRG with its ligated nerve and dorsal root attached was removed from the rat and placed in a chamber. Extracellular recordings were made from teased dorsal root fibers. Spontaneous activity (>0.05 imp/s in 3 min) originating within or close to the DRG was often found in C-, Adelta- and Abeta-fibers from nerve-injured rats, but was rare in fibers with peripheral axons from uninjured nerve. The incidence of various patterns of spontaneous discharge was similar to that previously recorded in vivo. Nineteen of 30 C-fibers, four of five Adelta- and three of seven Abeta-fibers from injured nerve responded to different doses of norepinephrine (NE) applied topically to the DRG. Five of seven C- and one of two Abeta -fibers from injured nerve responded to clonidine, a more selective alpha2 adrenergic agonist. The thresholds ranged from 500 to 10 microM, the lowest dose delivered. None of the fibers from uninjured nerve responded to NE or clonidine (500 microM). Since the experiments were carried out in vitro in the intact DRG, the existence of spontaneous activity in DRG cells in nerve-injured rats was independent of any blood borne chemicals, such as norepinephrine. We hypothesize that abnormal activity and adrenergic sensitivity in injured DRG neurons are due to an intrinsic alteration of the cell body membrane.     

Tenascin-C matrix assembly in oral squamous cell carcinoma

We previously showed that the extracellular matrix component tenascin-C (TN-C) is upregulated in oral squamous cell carcinoma (SCC) compared with the normal oral mucosa. In this study we examined oral biopsy specimens of mild to moderate dysplasia or carcinoma in situ to study TN-C expression. We found that carcinoma in situ is the stage at which TN-C becomes widely expressed, suggesting it may be involved in the initial stages of tumor progression. To study TN-C matrix production in vitro, we used an invasive oral SCC cell line (HSC-3) and peri-tumor fibroblasts (PTF). Neither cell type organized a TN-C matrix when cultured alone; however, when co-cultured with HSC-3 cells, PTF were able to assemble a TN-C matrix. PTF retained the ability to organize a TN-C matrix when separated from the HSC-3 cells by a semi-permeable membrane, indicating that cell-cell contact is not necessary for TN-C matrix organization and suggesting that soluble factors may be involved. Moreover, PTF were induced to assemble TN-C matrices when grown in medium conditioned by both the PTF and HSC-3 cells. Antibodies to fibronectin (FN) and to the first FN type III repeat blocked both FN and TN-C matrix assembly, indicating that TN-C matrix organization is dependent on an FN template. Antibodies to alpha5, alphav and beta1 integrins also blocked TN-C matrix formation. When seeded onto FN matrices, the co-cultures were unaffected by the anti-integrin and anti-FN antibodies and were able to organize a TN-C matrix. Our results suggest that progression of malignant oral SCC is accompanied by an alteration of the normal ECM to one rich in TN-C, and that the organization of a TN-C matrix is dependent on soluble cues provided by both the SCC cells and the PTF.     

A cell line (SCABER) derived from squamous cell carcinoma of the human urinary bladder

An established cell line derived from a documented squamous cell carcinoma of human urinary bladder is described. The cultured cells retained the characteristic morphology of the tumor of origin for 40 in vitro passages. Numerous desmosomes were found between cultured cells. Chromosome analysis showed hypotetraploidy with no obvious modal number, while distinctive marker chromosomes and a male karyotype were present.     

Lateral retropharyngeal node metastasis from carcinoma of the upper gingiva and maxillary sinus

Clinically unsuspected metastases to the lateral retropharyngeal nodes from carcinomas of the upper gingiva or maxillary sinus were found in five patients on follow-up CT examinations. Such uncommon metastases may follow the afferent lymphatic channels from the palate or pharyngeal region or arrive by retrograde lymphatics from positive neck nodes. Careful examination of lateral retropharyngeal nodes may be required in cancers of these primary sites.     

Fibroblast growth factor receptor expression reflects cellular differentiation in human oral squamous carcinoma cell lines

This study examined the expression of fibroblast growth factor receptor 2 (FGFR 2) splice variants, IIIb and IIIc, in normal and malignant human oral keratinocytes and in normal oral fibroblasts by RT-PCR using both exon-specific primers and primers common to both FGFR 2 isoforms. Fibroblasts expressed exclusively FGFR 2/IIIc whilst the normal and malignant keratinocytes co-expressed FGFR 2/IIIb and FGFR 2/IIIc. Well-differentiated keratinocytes expressed proportionally more FGFR 2/IIIb than IIIc whereas the poorly-differentiated cells expressed more FGFR 2/IIIc than IIIb. The normal and malignant keratinocytes, but not fibroblasts, expressed an additional amplification product, which consisted of both IIIb and IIIc of FGFR 2 joined by an extra base pair and with the intronic sequence removed. The results indicate that the expression of FGFR 2 isoforms reflects the degree of cellular differentiation in normal and malignant human oral keratinocytes and that receptor complexes of FGFR 2/IIIb and IIIc may regulate ligand-receptor interactions.     

Oral squamous cell carcinoma: new insights

Squamous cell carcinoma is the most common form of oral cancer, and causes more deaths than any other oral disease. Dentists and dental auxiliaries must know the clinical, etiologic, pathogenetic and prognostic features of squamous cell carcinoma to ensure appropriate screening and diagnosis of the patient. It is now recognized that cancers are genetic diseases, which arise from inherited genetic factors and exposure to exogenous carcinogens that alter the DNA of cells. Increasingly, the genetic events that contribute to the development of cancers at many sites within the body are being identified, and the complex series of genetic steps required for fully-developed neoplasia to arise in the oral cavity are being better characterized. This article reviews recent advances in the understanding of the etiology and pathogenesis of oral carcinoma, including the involvement of various oncogenes, tumor suppressor genes and viruses.