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PubMedDate not supplied

Clinical significance of laminin deposition and T-cell infiltration in oral cancer.

Biopsied specimens from 55 patients with squamous cell carcinoma (SCC) of the oral cavity were examined immunohistopathologically as to the clinical significance of basement membrane (BM) deposition and T-cell infiltration at the tumor-stromal border using monoclonal anti-laminin and anti-CD3 antibodies. According to the immunoreactivity, all specimens could be divided into three groups: group A, a continuous linear pattern of positive staining for BM around tumor nests; group B, an alteration of BM deposition around tumor nests with T cell infiltration into those tumor nests; and group C, an alteration of BM deposition around tumor nests without T cell infiltration into those tumor nests. These groups were correlated with clinical manifestations, such as tumor size, tumor regression rate with induction chemotherapy, and regional lymph node metastatic rate. In these groups, tumors classified as group C showed a trend toward resistance to chemotherapy and high metastatic characteristics. Tumors classified as group B, which showed the same alteration of BM deposition as a result of T cell infiltration into the tumor nests, showed a sufficient tumor regression rate with chemotherapy. The visualization of the staining for BM laminin and T cells in oral SCC appeared not only to increase our understanding of the biologic and clinical behavior of individual tumors, but could be a prognostic indicator.

Antibodies, Monoclonal↗
PubMedDate not supplied

In situ skin grafting of free muscle flaps prior to microvascular transfer to provide intraoral lining for full-thickness defects.

BACKGROUND: Previously, the importance of providing skin for intraoral lining for full-thickness mucocutaneous defects has been emphasized. More recently, simple skin grafting of the intraoral portion of muscle flaps has been described. METHODS: Six patients were evaluated who had full-thickness mucocutaneous defects reconstructed by means of free muscle flaps with skin grafting of the intraoral muscle surface. An illustrative case is provided. A technique of preplacing the skin graft on the muscle prior to microvascular transfer is described. Mucosal biopsies were performed at the reconstruction site. RESULTS: All patients had complete take of the skin grafts. No fistulas occurred. Functional and esthetic results were satisfactory. CONCLUSIONS: The ideal candidate for this form of reconstruction is one in whom there is a large, full-thickness mucocutaneous defect. Preplacement of the skin graft reduces ischemia time, allows suturing of the skin graft to the muscle surface outside the narrow confines of the oral cavity, and enables placement of multiple quilting sutures that secure the graft against shear forces and so obviate the need for a stent dressing.

Aged↗
PubMedDate not supplied

Extent of lymph node dissection in T3/T4 cancer of the alveolo-buccal complex.

BACKGROUND: Cancer of the alveolo-buccal complex even when locally advanced is amenable to curative resection. However, the extent of lymph node dissection remains controversial. METHODS: A total of 181 patients with T3/T4 cancer of the alveolo-buccal complex who underwent a radical neck dissection (RND) were analyzed retrospectively to determine the incidence and pattern of lymph node involvement and to define the extent of neck dissection required in these cancers. RESULTS: Lymph node involvement was as follows: level I (85%), II (51%), III (19%), IV (18%), V (5%). Levels I and II were most commonly involved (94%). Skip metastases occurred in 13%. Levels IV and V were involved in 2% and 20% when levels I, II, and III were uninvolved and involved, respectively. CONCLUSION: A supraomohyoid neck dissection (SOHD) should be performed and subjected to a frozen section evaluation in every patient. If lymph nodes are negative, then SOHD is adequate. If levels I, II, or III are positive, then a RND should be performed.

Alveolar Process↗
PubMedDate not supplied

Alterations in levels of different protein kinase C isotypes and their influence on behavior of squamous cell carcinoma of the oral cavity: epsilon PKC, a novel prognostic factor for relapse and survival.

BACKGROUND: Recent results suggest that some PKC isotypes, when overexposed, confer to cultured fibroblasts certain proliferative advantages, and enhanced tumorigenicity in nude mice, suggesting their participation in carcinogenic process. These findings need to be validated through the investigation of potential alterations of these kinases in common forms of human cancers. MATERIAL AND METHODS: In this prospective study we determined levels of different PKC isozymes by Western blot in tissue extracts from 29 human primary squamous cell carcinomas of the oral cavity, and their respective controls. These expressions were correlated with behavior of tumor and histologic characteristics. RESULTS: Dramatic alterations in different PKC isotypes were found. Thus, increased levels of isotypes alpha, beta, or gamma, and zeta were found in most of the patients, as well as significant correlations between levels of the isotype epsilon and survival-relapse rate and classical PKC isotypes with irregular morphology of tumoral interphase. CONCLUSIONS: These results suggest participation of some PKC isotypes (alpha, beta, gamma, and zeta) in the genesis and behavior (epsilon) of oral cancers. Levels of epsilon PKC could be used as prognostic marker.

Adult↗
PubMedDate not supplied

Metastatic carcinoma of oral soft tissue.

Metastatic carcinomas to the oral region are rare. Most of the lesions are located in the bones of the jaw. The medical literature contains quite a few examples of metastatic lesions located strictly in the oral soft tissue. We present two cases of oral soft tissue metastatic carcinoma of urogenital origin.

Adenocarcinoma↗
PubMed2003

Stromelysin-3 expression is an early event in human oral tumorigenesis.

Stromelysin-3 (ST3/MMP11) is associated with human tumour progression. To determine the clinical significance of ST3 in oral tumorigenesis, its expression was analysed in different stages of tobacco-associated oral cancer. Immunohistochemical analysis of ST3 expression in 79 oral precancerous lesions, 177 SCCs and 35 histologically normal oral tissues was carried out and corroborated by immunoblotting and RT-PCR. ST3/MMP11 protein expression was observed in 45/79 (57%) precancerous lesions [28/48 (58%) with hyperplasia and 17/31 (55%) with dysplasia] and in 123/177 (70%) oral SCCs. In precancerous lesions, ST3 expression was higher compared to normal oral tissues (p = 0.000) and associated with MVD (p = 0.05), a marker for angiogenesis. ST3 was also expressed in cells cultured from precancerous and cancerous lesions that had undergone epithelial-to-mesenchymal transition. In oral cancer patients, ST3 positivity was associated with lymph node involvement (p = 0.025) and increased intratumoral MVD (p = 0.009). Ninety-eight oral SCC patients were followed up for a period of 94 months (median 22.5 months). Kaplan-Meier survival analysis showed that ST3 expression was not a significant prognostic indicator. ST3 expression in oral hyperplastic and dysplastic lesions suggests its association with progression of phenotypic alterations acquired early during the malignant transformation pathway of oral epithelium and implicates it not only in angiogenesis and invasion but also in tumorigenesis. Thus, ST3 may serve as a potential target for developing molecular therapeutics for early intervention in oral tumorigenesis.

Adult↗
PubMed2003

Piroxicam selectively inhibits the growth of premalignant and malignant human oral cell lines by limiting their progression through the S phase and reducing the levels of cyclins and AP-1.

Studies have shown that nonsteroidal antiinflammatory drugs (NSAIDs) reduce the risk of and mortality from a variety of cancers. Although cyclooxygenase (COX)-dependent and -independent pathways may be involved, the mechanisms responsible for these effects remain unknown. In our study, we found that piroxicam inhibited cell growth in premalignant and malignant, but not normal, human oral epithelial cell lines in a concentration- and time-dependent manner. After 6 days of exposure, the concentration that inhibited growth by 50% was 181 and 211 microM for premalignant and malignant cells, respectively. Piroxicam did not induce apoptosis. The growth inhibitory effect was COX and PGE2 independent. Adding PGE2 or infecting cells with a COX-1 transgene did not abrogate piroxicam-induced growth inhibition. After treatment of the premalignant and malignant cell lines with piroxicam, cells accumulated in the S phase of the cell cycle. Upon removal of piroxicam, cells entered the G2 phase. The S phase block was accompanied by a reduction in the protein levels of cyclin A, cyclin B1, cyclin D1, cdc2, PCNA and the c-jun AP-1 component. Therefore, piroxicam may exert its growth inhibitory effects selectively on the premalignant and malignant human oral epithelial cells lines via signaling pathways regulating the progression of cells through the S phase of the cell cycle.

Base Sequence↗
PubMed2006

Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin gamma-2 chain is an early coordinated event in incipient oral squamous cell carcinoma.

Cancer cell invasion is facilitated by extracellular matrix degrading proteases such as plasmin. We have studied the expression of plasminogen activator inhibitor-1 (PAI-1) and urokinase receptor (uPAR) together with the gamma2-chain of laminin-5 (lam-gamma2) by immunohistochemistry in 20 cases with incipient oral squamous cell carcinoma (SCC). PAI-1-positive neoplastic cells located at the tip of the putative invasive front of grade 1 (incipient) carcinoma were seen in 16 of the 20 cases (75%), whereas adjacent normal and dysplastic epithelium was PAI-1-negative. Clusters of putative invasive neoplastic cells located in the lamina propria were PAI-1-positive in areas with grade 2 incipient carcinoma as were invasive cancer cells in areas of grade 3-4 invasive carcinoma. uPAR immunoreactivity was strongly expressed in numerous stromal cells in the carcinoma area in all 20 lesions, while a few uPAR-positive stromal cells were found in areas with normal and dysplastic epithelium. uPAR-positive neoplastic cell islands located at the front of the lesions were seen in 15 of the 20 cases. The expression pattern of lam-gamma2 was very similar to that of PAI-1; however, lam-gamma2-positive neoplastic cells were only detected in 11 of the 20 cases (55%) in areas of grade 1 incipient carcinoma. Direct comparison of the 3 components revealed colocalization in neoplastic cell islands in both incipient and invasive SCC. Our results suggest that PAI-1 is a novel potential marker of initial invasion in oral SCC, and that the coordinated expression of PAI-1 with uPAR and lam-gamma2 sustain the features of the early invasive cancer cells.

Biomarkers, Tumor↗
PubMed1992

Expression of histo-blood-group-A/B-gene-defined glycosyltransferases in normal and malignant epithelia: correlation with A/B-carbohydrate expression.

Malignant transformation of oral and bladder epithelia is often associated with loss of histo-blood-group-A- and -B-carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A- and B-carbohydrate antigens with that of the A/B-gene-defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti-A/B-transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A- and B-carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B-transferase proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A- and B-carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes.

ABO Blood-Group System↗
PubMed1994

TGF-beta receptor regulation mediates the response to exogenous ligand but is independent of the degree of cellular differentiation in human oral keratinocytes.

This study examined the expression of TGF-beta cell-surface receptors, the response to exogenous TGF-beta 1 and the autocrine production of TGF-beta in normal and squamous cell carcinoma-derived human oral keratinocytes with variable degrees of cellular differentiation. TGF-beta receptor expression, the response to exogenous ligand and the autocrine production of TGF-beta appeared unrelated to cellular differentiation. Cells expressed variable proportions of type-I, -II and -III TGF-beta receptors. The expression of type-III receptors correlated inversely with the expression of type-I receptors, but there was no relationship between type-II and either type-I or type-III TGF-beta receptors. Normal cells and the majority (7 of 8) of tumour-derived keratinocytes were inhibited by exogenous TGF-beta 1 and the degree of inhibition correlated with the expression of type-I, but not type-II or type-III, TGF-beta receptors. One tumour-derived cell line was refractory to exogenous TGF-beta 1 although it expressed all 3 receptor types. Endogenous TGF-beta was produced by both normal and tumour-derived keratinocytes and correlated inversely to the expression of type-I, but not type-II, TGF-beta receptors. Further, cells that produced more autocrine TGF-beta had a diminished response to exogenous TGF-beta 1. The data indicate a complex interaction between the expression of TGF-beta cell-surface receptors, endogenous ligand production and the cellular response to exogenous TGF-beta 1.

3T3 Cells↗
PubMed1999

Experimental intervention study about recognition of erythroplakia by undergraduate dental students.

The aim of this study was to assess the efficacy of an examiners' training programme applied to identification of erythroplakia, which undergraduate dental students have found particularly difficult. An experimental group of 5th year undergraduate dental students received a pictorial handout with diagnostic criteria for oral red lesions and two, one hour-long diagnostic seminars in which oral erythroplakia was discussed, together with other red lesions with similar clinical appearance. Three months later a set of 16 photographic slides depicting previously pathologically diagnosed red lesions were projected. Sensitivity, specificity and agreement were all higher for the experimental group compared to a control group. It is suggested that teaching procedures using slides could be useful for training future examiners at recognizing oral erythroplakias.

Audiovisual Aids↗
PubMed1975

Cervical-pectoral flaps in the treatment of advanced oral cancer.

Twenty-two of 90 patients with carcinoma of the anterior oral cavity treated at the Minneapolis Veterans Administration Hospital from 1965 through 1973 had advanced lesions - tumors attached to the mandible and/or more than 3 cm in size. These patients were treated by primary radical neck dissection, en bloc excision, and segmental mandibulectomy. A cervical-pectoral flap combination was used for reconstruction. The functional and cosmetic results were excellent. Patient survival and cure rate compare favorably with other series. We emphasize the need for wide initial resection with immediate reconstruction.

Adult↗
PubMed1978

Intraoral basal cell carcinoma.

The evaluation and treatment of an intraoral lesion over a period of 8 years is presented. Clinical appearance and course, microscopic findings, and response to treatment were consistent with a diagnosis of basal cell carcinoma of the mucous membrane. Current theories of histogenesis and the biological behavior of basal cell lesions are discussed.

Adult↗
PubMed2005

Identification of differentially expressed genes in oral squamous cell carcinoma.

Rapid advances in multimodality therapy have not significantly improved the overall 5-yr survival of oral cancer patients in the past two decades, thereby underscoring the need for molecular therapeutics. The development of new treatment strategies for more effective management of oral cancer requires identification of novel biological targets. Therefore, the aim of this study was to identify novel genes associated with oral tumorigenesis by comparing gene expression profile of oral squamous cell carcinomas (OSCCs) and matched nonmalignant oral epithelial tissues with differential display. Of the 180 differentially expressed cDNAs isolated, reamplified, and cloned into pGEMT-Easy Vector, 26 cDNAs were confirmed to be upregulated in OSCCs by reverse Northern blot analysis. The differentially expressed genes included components of immune system, signaling pathways, angiogenesis, cell structure, proliferation, apoptosis, cell-adhesion, and cellular metabolism. Reverse transcription (RT)-polymerase chain reaction (PCR) analysis of 15 OSCCs and matched nonmalignant oral tissues provided the first evidence that 14-3-3-zeta, melanoma metastasizing clone D (MEMD), KIAA0471, sperm protein 17 (SP17), TC21, and anti-TNF alpha antibody are upregulated in OSCCs. Immunohistochemical analysis confirmed overexpression of 14-3-3-zeta and TC21 protein, a member of the Ras family, in OSCCs as compared to histologically normal oral tissues validating the differential display analysis. Identification of six novel differentially expressed genes in oral tumors adds to the repertoire of genes associated with oral carcinogenesis and provides candidate potential biological targets for diagnosis and/or therapy. Further characterization of the 14 unknown differentially expressed cDNAs identified in this study may provide significant clues for understanding the molecular mechanisms underlying oral tumorigenesis.

14-3-3 Proteins↗