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Reactivity of monoclonal antibody 17.13 with oral lichen planus
ORAL SURGERY ORAL MEDICINE ORAL P A T H O L O G Y Volume 80, Number 4 mation or degree of atrophy. The results of this study suggest biologic evidence for the slightly increased risk for progression of lichen planus to squamous cell carcinoma that has been noted in the literature. Alternately, or concomitantly, it suggests a clear-cut biological basis for a true diagnosis of lichenoid dysplasia. It is suggested that for cases with a histologic diagnosis of lichen planus, lichenoid mucositis, lichenoid keratosis, or lichenoid dysplasia, routine use of p53 immunostaining could enhance the identification of those patients with a lichenoid process who are at greatest risk for malignant transformation.
Abstracts. A A O P
455
carcinomas as well as those exhibiting differentiation of varying degrees. Plasma membrane immunoreactivity was not observed in any of the investigated tumors. Seven of the investigated tumors showed positive immunoreactivity both for C-erbB-2 and p53. CerbB-2 expression has been reported in biologically more aggressive adenocarcinomas with poor prognosis, but its status in oral squamous cell carcinomas is currently unknown. Furthermore. co-expression of C-erbB-2 and p53 was observed, but the implications in tumor pathogenesis, if any, remain to be elucidated. POLYMORPHOUS LOW GRADE ADENOCARCINOMA: FLOW CYTOMETRIC, P53 AND PCNA ANALYSIS. R. Kelsch. T. Bhuiya,
EXPRESSION OF P53, KI67, AND CYTOKERATIN-4 IN ORAL PAPILLOMAS. M.A. Copete, K. Wendt, S.-Y. Chen. Temple University, Philadelphia, Pa. The wild-type p53 suppressor gene controls cell proliferation at the G1/S checkpoint. The mutant-type p53 has lost the inhibitory function and is overexpressed in over 50% of all cancers. Previous studies showed that p53 was also overexpressed in oral papillomas. The purpose of this study was to investigate the expression of p53 in a group of 30 oral papillomas. The expression of Ki67 and keratin-4 was also investigated to determine the proliferative activity and cytodifferentiatior, respectively. Formalinfixed paraffin-embedded sections were processed for immunohistochemistry, using an avidin-biotin-peroxidase complex procedure and monoclonal antibodies. Twenty eight (93%) of 30 papilloma specimens were positive for p53. The percentage of p53-positive cells in the basal layer was 60.4 -+ 14.8 (mean - SD, N = 28) with a range of 34.6 to 92.1. The percentage of Ki67-positive cells in the basal layer was quite variable, being 26.7 + 14.4 (mean - SD, N = 28) with a wide range of 1.1 to 64.6. There was no correlation between overexpression of p53 and the expression of Ki67. Expression of keratin-4 in the differentiating spinous cells was delayed two to three cell rows away from the basement membrane by the expansion of proliferative cells. Results indicate that overexpression of p53 occurs in most oral papillomas and that papillomas undergo cytokeratin differentiation similar to the parent tissue.
A. Fuchs. P. Gentile. M. Kahn. J. Fantasia. Long Island Jewish Medical Center, New Hyde Park, N.Y. and University of Tennessee. Memphis. Polymorphous low grade adenocarcinoma of minor salivary glands (terminal duct carcinoma, lobular carcinoma) is a recently defined entity. A 17% recurrence rate and a 9% metastasis rate have been reported. Fourteen formalin-fixed, paraffin-embedded archival cases were analyzed. Ploidy and proliferative activity were evaluated with flow cytometric analysis. Demonstration of an abnormal p53 gene product, and proliferative cell nuclear antigen (PCNA) analyses were also performed with routine immunohistochemical procedures. The purpose of this investigation was to evaluate these parameters and determine if a correlation existed. Flow cytometry was performed on ten cases with three showing an aneuploid cell line (mean S-phase% of diploid tumor cells 5.9, aneuploid S-phase% 26.7). Products of a mutation o f the p53 tumor suppressor gene have been noted to accumulate in salivary gland tumors, both benign and malignant. Qualitative assessment revealed p53 positive staining in four of fifteen tumors; positive cells comprised 5% to 10% of the tumor. The percentage of tumor cells positive for PCNA staining ranged from 0.5% to 70%. There was no correlation between proliferative activity as determined by PCNA when compared to results of flow cytometric analysis except for one case that exhibited p53 staining, a 26% PCNA fraction, and a distinct aneuploid cell line.
EXPRESSION OF C-ERB-2 AND P53 ONCOPROTEINS IN SQUAMOUS CELL CARCINOMAS: A CORRELATIVE IMMUNOHISTOCHEMICAL STUDY, B. Singh, H. McCampbell, B. Whitaker, F. Chandler Jr. Medical College of Georgia, Augusta. The initiation and progression of malignant oral neoplasms has been subject of investigations over the years; however, the involved molecular mechanisms remain unknown. In this regard a number of studies on the status of various oncogenes such as p53 and others have been forthcoming but studies on C-erbB-2 are lacking and'the available data are rather conflicting. Therefore, it was considered pertinent to examine the expression of C-erbB-2 oncoprotein and correlate with that of p53. For this purpose 5 thick sections of formalin-fixed tumors from archival paraffin blocks were examined with immunohistochemical techniques using monoclonal antibodies (Abs). The application of Abs (1801 and DO7) to p53 oncoproteins revealed positive nuclear and cytoplasmic staining in 20 (n = 35) squamous cell carcinomas with 10 exhibiting intense staining. Many neoplastic cells showed reactivity in poorly differentiated areas of squamous cell carcinomas whereas differentiating areas exhibited a heterogenous positive reaction. In addition advancing fronts of the tumors generally exhibited nuclear staining and the contiguous areas of epithelial dysplasia were also positive in few cases. C-erbB-2 oncoprotein employing Abs CB 11 exhibited cytoplasmic immunoreactivity of varYing degree in 12 carcinomas (n = 25). The positive immunoreactivity was generally noticed in both the poorly differentiated
REACTIVITY OF MONOCLONAL ANTIBODY 17.13 WITH ORAL LICHEN PLANUS. A. Leider, P. Merrell, S. Silverman Jr, W. Carpenter, J. Gallo. University of the Pacific and University of California, San Francisco. Monoclonal antibodies (MAbs) 17,13 and 63.12 exhibit characteristic reactivity patterns in normal stratified squamous epithelium that have been shown to have a high degree of sensitivity and specificity with oral squamous cell carcinoma. A recently reported study suggested that an altered immunoreactivity of MAb 17.13 may correlate well with morphologic epithelial dysplasia, m a y precede identifiable dysplastic change in some hyperkeratotic lesions, and may correlate with the presence of "lichenoid" inflammation in clinical leukoplakia/erythroleukoplakia. The purpose of the present study was to assess the immunoreactivity of MAb 17.13 in clinical oral lichen planus (OLP) and to compare this reactivity with that reported in clinical leukoplakia/erythroleukoplakia. Biopsies were performed in the Oral Medicine Clinic at UCSF on 14 patients who had previously met accepted clinical criteria for the diagnosis o f OLP. All cases also met rigid histomorphologic criteria for lichen planus through evaluation by three oral pathologists of formalin-fixed H&E sections. These criteria included hyperorthokeratosis or hyperparakeratosis, liquefaction degeneration of the basal cell layer, no evidence of epithelial dysplasia, an eosinophilic thickening of the basement membrane, and a dense band-like lymphoreticular subepithelial inflammatory in-
456
Abstracts, AAOP
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY October 1995
filtrate that failed to extend to the underlying tissues. One half of each biopsy specimen was stained with H & E and the other half was frozen for reaction with M A b 17.13. 63.12 and a,control antibody. Results were assessed by recording the immunoreactivity of each M A b in the various layers of surface epithelium. M A b 17. l 3 reacted in all cases of OLP in almost an identical pattern to that reported in the previous study with epithelial dysplasia. These findings demonstrate that the altered immunoreactivity of M A b 17.13 is similar in OLP and oral epithelial dysplasia and further support the concept of OLP as a premalignant condition. IMMUNOHISTOCHEMICAL STUDY OF LANGERHANS' CELLS IN ORAL SQUAMOUS CELL CARCINOMA IN YOUNG AND OLD PATIENTS. D. Cleveland. J. Stewart. Temple University and University of Pennsylvania. Philadelphia. Pa. Langerhans' cells (LCs) are dendritic cells that reside in epithelium and serve important immunologic functions. Accumulating evidence suggests that they m a y be involved in the pathogenesis of some skin and mucosal diseases. Because recent reports have described an increase in squamous cell carcinoma (SCC) of the oral cavity in young adults, we designed an immunoperoxidase study to ascertain whether there are quantitative differences in LCs in SCC in patients 40 years of age or less and patients greater than 40 years of age. All cases of SCC were retrieved from the archives of Temple University Oral Pathology Laboratory as formalinfixed and paraffin-embedded tissue. There were 21 cases of SCC in the under 40 age group (14 to 40 years, age range; 33 years, average age) and 19 cases of SCC in the over 40 age group (53 to 88 years, age range; 70 years, average age). The most c o m m o n location of SCC for both age groups was the lateral tongue. LCs were immunostained for S-100 protein and H L A - D R antigen and counted as the number of positively staining cells (having at least one dendrite per cell body) per millimeter o f epithelial surface length (ESL). Results: For the over-40 age group the mean value o f S-100 positive cells was 7.77 cells/ESL and the mean value of H L A - D R positive ceils was 1.81 cellsfESL: for the under-40 age group the m e a n value of S-100 positive cells was 8.97 cells/ESL and the m e a n value of H L A - D R positive ceils was 1.99 cells/]ESL. Statistical analysis of the data (student's t test) failed to disclose a statistically significant difference between the mean values for either of the markers studied (S- 100:p = 0.55: H L A - D R : p = 0.79). Our data suggest that quantitative variations in LC numbers do not contribute significantly to differences in pathogenesis of SCC in young versus old patients. IMMUNOHISTOCHEMICAL EVALUATION OF TRANSFORMING GROWTH FACTOR BETA IN OSTEOSARCOMAS OF THE JAWS AND ITS POTENTIAL ROLE IN TUMOR PROLIFERATION. J. Tiffee, T. Aufdemorte. University of Texas Health Science Center, San Antonio. Transforming growth factor beta fTGF-13) is a cytokine with numerous functions in several different tissues. The largest source of TGF-[3 in h u m a n s is bone: TGF-[3 has been shown to stimulate bone formation via Type I collagen production and influences several other metabolically active bone proteins. Also, studies on cell cultures have shown both inhibitory and stimulatory effects of TGF-[3 on osteosarcoma cells. However, very little information is available as to the level of expression of TGF-13 in h u m a n osteosarcoma tissue. The purpose of this study was to retrospectively evaluate a series of osteosarcomas for the presence of intracellular TGF-I3. To this end, formalin-fixed paraffin-embedded tissue from four chondroblastic osteosarcomas of the jaws were retrieved
from our files. Sections were then evaluated immunohistochemically using a polyclonal antibody against TGF-I~ subtypes 1.2. and 3. This assessment revealed positive reactivity by tumor cells in all cases. However. the better differentiated tumors showed a greater number of positive ceils, so that lesions with greater differentiation possessed a greater level of intracellular TGF-13. This data would tend to support the conclusions drawn by others that further study is necessary to more thoroughly evaluate the significance of TGF-13 in both neoplastic and nonneoplastic lesions of bone. ULTRASTRUCTURAL DEMONSTRATION OF MYOF|BROBLASTIC FEATURESIN CELL CULTURE OF A CENTRAL ODONTOGENIC FIBROMA. F. Kratochvil, J. Schwartz. M. Cardinali. Naval Dental School and National Institute of Dental Research. Bethesda. Md. Myofibroblasts are considered to be responsible for tissue contraction during wound healing and the desmoplastic response to s o m e carcinomas, i.e. breast cancer. Mucosal retraction, producing a palatal mucosal cleft, is often seen with central odontogenic fibromas ~COF) of the anterior maxilla. W e searched for features of myofibroblastic differentiation in a cell culture of a COF that showed prominent palatal mucosal clefting. Ultrastructural examination by transmission electron microscopy showed arrays of intermediate filaments with focal densities. In addition, these cells demonstrated subplasmalemmal micropinocytotic vesicles, external lamina, and intercellular junctions. Demonstration of myofibroblastic features in this neoplasm m a y help explain the interesting and unique clinical feature of mucosal clefting that some of these tumors express. Also. this appears to represent the first report of a viable cell culture of a COF. OXIDANT STRESSSYNERGISM IN AIDS-KS PATHOGENESIS S Mallery, R. Bailer, C. Ng-Bautista. C. Hohl, G. Ness, G. Brierley. The Ohio State University, Columbus. Despite its recognition as the most prevalent HIV-associated neoplasm, speculation still abounds regarding the pathogenesis of AIDS-related Kaposi's sarcoma ~AIDS-KS). However, it has been established that both cytokines e.g. IL-6, and HIV-associated products e.g. Tat. are integral in AIDS-KS cellular proliferation. Further. both experimental and clinical evidence is accumulating to link reactive oxygen intermediates (ROD with both cytokine induction (via both NF-KB dependent and NF-KB independent routes) as well as the subsequent cytokine (TNFc~) stimulation of HIV replication. Features o f AIDS-KS patients, such as retention of their phagocytes, presence of sustained immunostimulation. and a frequent history of a KS lesion arising at a traumatized site. make oxidant stress a viable clinical factor in AIDS-KS development. The objective of this study was to monitor, via time course nucleotide analyses. AIDS-KS cellular bioenergetic response to physiologically relevant levels of H202. Our nucleotide profiles show that AIDS-KS cells have an inherent, statistically significant biochemical deficit, e.g. lower levels of high energy phosphates. glutathione, and NADPH, even prior to oxidant stress. Following exposure to H202, only the h u m a n microvascnlar endothelial cells (a putative KS progenitor cell) responded with beneficial bioenergetic adaptations that reflected co-ordination o f energy generating and cytoprotective pathways. Also, some o f the AIDS-KS strains retained intracellular GSSG subsequent to oxidant challenge, inviting the formation of deleterious protein mixed disulfides. Therefore institution of antioxidant therapy (low-risk/ potential high-benefit) m a y prove beneficial in preventing disease progression.
Abstracts. A A O P
455
carcinomas as well as those exhibiting differentiation of varying degrees. Plasma membrane immunoreactivity was not observed in any of the investigated tumors. Seven of the investigated tumors showed positive immunoreactivity both for C-erbB-2 and p53. CerbB-2 expression has been reported in biologically more aggressive adenocarcinomas with poor prognosis, but its status in oral squamous cell carcinomas is currently unknown. Furthermore. co-expression of C-erbB-2 and p53 was observed, but the implications in tumor pathogenesis, if any, remain to be elucidated. POLYMORPHOUS LOW GRADE ADENOCARCINOMA: FLOW CYTOMETRIC, P53 AND PCNA ANALYSIS. R. Kelsch. T. Bhuiya,
EXPRESSION OF P53, KI67, AND CYTOKERATIN-4 IN ORAL PAPILLOMAS. M.A. Copete, K. Wendt, S.-Y. Chen. Temple University, Philadelphia, Pa. The wild-type p53 suppressor gene controls cell proliferation at the G1/S checkpoint. The mutant-type p53 has lost the inhibitory function and is overexpressed in over 50% of all cancers. Previous studies showed that p53 was also overexpressed in oral papillomas. The purpose of this study was to investigate the expression of p53 in a group of 30 oral papillomas. The expression of Ki67 and keratin-4 was also investigated to determine the proliferative activity and cytodifferentiatior, respectively. Formalinfixed paraffin-embedded sections were processed for immunohistochemistry, using an avidin-biotin-peroxidase complex procedure and monoclonal antibodies. Twenty eight (93%) of 30 papilloma specimens were positive for p53. The percentage of p53-positive cells in the basal layer was 60.4 -+ 14.8 (mean - SD, N = 28) with a range of 34.6 to 92.1. The percentage of Ki67-positive cells in the basal layer was quite variable, being 26.7 + 14.4 (mean - SD, N = 28) with a wide range of 1.1 to 64.6. There was no correlation between overexpression of p53 and the expression of Ki67. Expression of keratin-4 in the differentiating spinous cells was delayed two to three cell rows away from the basement membrane by the expansion of proliferative cells. Results indicate that overexpression of p53 occurs in most oral papillomas and that papillomas undergo cytokeratin differentiation similar to the parent tissue.
A. Fuchs. P. Gentile. M. Kahn. J. Fantasia. Long Island Jewish Medical Center, New Hyde Park, N.Y. and University of Tennessee. Memphis. Polymorphous low grade adenocarcinoma of minor salivary glands (terminal duct carcinoma, lobular carcinoma) is a recently defined entity. A 17% recurrence rate and a 9% metastasis rate have been reported. Fourteen formalin-fixed, paraffin-embedded archival cases were analyzed. Ploidy and proliferative activity were evaluated with flow cytometric analysis. Demonstration of an abnormal p53 gene product, and proliferative cell nuclear antigen (PCNA) analyses were also performed with routine immunohistochemical procedures. The purpose of this investigation was to evaluate these parameters and determine if a correlation existed. Flow cytometry was performed on ten cases with three showing an aneuploid cell line (mean S-phase% of diploid tumor cells 5.9, aneuploid S-phase% 26.7). Products of a mutation o f the p53 tumor suppressor gene have been noted to accumulate in salivary gland tumors, both benign and malignant. Qualitative assessment revealed p53 positive staining in four of fifteen tumors; positive cells comprised 5% to 10% of the tumor. The percentage of tumor cells positive for PCNA staining ranged from 0.5% to 70%. There was no correlation between proliferative activity as determined by PCNA when compared to results of flow cytometric analysis except for one case that exhibited p53 staining, a 26% PCNA fraction, and a distinct aneuploid cell line.
EXPRESSION OF C-ERB-2 AND P53 ONCOPROTEINS IN SQUAMOUS CELL CARCINOMAS: A CORRELATIVE IMMUNOHISTOCHEMICAL STUDY, B. Singh, H. McCampbell, B. Whitaker, F. Chandler Jr. Medical College of Georgia, Augusta. The initiation and progression of malignant oral neoplasms has been subject of investigations over the years; however, the involved molecular mechanisms remain unknown. In this regard a number of studies on the status of various oncogenes such as p53 and others have been forthcoming but studies on C-erbB-2 are lacking and'the available data are rather conflicting. Therefore, it was considered pertinent to examine the expression of C-erbB-2 oncoprotein and correlate with that of p53. For this purpose 5 thick sections of formalin-fixed tumors from archival paraffin blocks were examined with immunohistochemical techniques using monoclonal antibodies (Abs). The application of Abs (1801 and DO7) to p53 oncoproteins revealed positive nuclear and cytoplasmic staining in 20 (n = 35) squamous cell carcinomas with 10 exhibiting intense staining. Many neoplastic cells showed reactivity in poorly differentiated areas of squamous cell carcinomas whereas differentiating areas exhibited a heterogenous positive reaction. In addition advancing fronts of the tumors generally exhibited nuclear staining and the contiguous areas of epithelial dysplasia were also positive in few cases. C-erbB-2 oncoprotein employing Abs CB 11 exhibited cytoplasmic immunoreactivity of varYing degree in 12 carcinomas (n = 25). The positive immunoreactivity was generally noticed in both the poorly differentiated
REACTIVITY OF MONOCLONAL ANTIBODY 17.13 WITH ORAL LICHEN PLANUS. A. Leider, P. Merrell, S. Silverman Jr, W. Carpenter, J. Gallo. University of the Pacific and University of California, San Francisco. Monoclonal antibodies (MAbs) 17,13 and 63.12 exhibit characteristic reactivity patterns in normal stratified squamous epithelium that have been shown to have a high degree of sensitivity and specificity with oral squamous cell carcinoma. A recently reported study suggested that an altered immunoreactivity of MAb 17.13 may correlate well with morphologic epithelial dysplasia, m a y precede identifiable dysplastic change in some hyperkeratotic lesions, and may correlate with the presence of "lichenoid" inflammation in clinical leukoplakia/erythroleukoplakia. The purpose of the present study was to assess the immunoreactivity of MAb 17.13 in clinical oral lichen planus (OLP) and to compare this reactivity with that reported in clinical leukoplakia/erythroleukoplakia. Biopsies were performed in the Oral Medicine Clinic at UCSF on 14 patients who had previously met accepted clinical criteria for the diagnosis o f OLP. All cases also met rigid histomorphologic criteria for lichen planus through evaluation by three oral pathologists of formalin-fixed H&E sections. These criteria included hyperorthokeratosis or hyperparakeratosis, liquefaction degeneration of the basal cell layer, no evidence of epithelial dysplasia, an eosinophilic thickening of the basement membrane, and a dense band-like lymphoreticular subepithelial inflammatory in-
456
Abstracts, AAOP
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY October 1995
filtrate that failed to extend to the underlying tissues. One half of each biopsy specimen was stained with H & E and the other half was frozen for reaction with M A b 17.13. 63.12 and a,control antibody. Results were assessed by recording the immunoreactivity of each M A b in the various layers of surface epithelium. M A b 17. l 3 reacted in all cases of OLP in almost an identical pattern to that reported in the previous study with epithelial dysplasia. These findings demonstrate that the altered immunoreactivity of M A b 17.13 is similar in OLP and oral epithelial dysplasia and further support the concept of OLP as a premalignant condition. IMMUNOHISTOCHEMICAL STUDY OF LANGERHANS' CELLS IN ORAL SQUAMOUS CELL CARCINOMA IN YOUNG AND OLD PATIENTS. D. Cleveland. J. Stewart. Temple University and University of Pennsylvania. Philadelphia. Pa. Langerhans' cells (LCs) are dendritic cells that reside in epithelium and serve important immunologic functions. Accumulating evidence suggests that they m a y be involved in the pathogenesis of some skin and mucosal diseases. Because recent reports have described an increase in squamous cell carcinoma (SCC) of the oral cavity in young adults, we designed an immunoperoxidase study to ascertain whether there are quantitative differences in LCs in SCC in patients 40 years of age or less and patients greater than 40 years of age. All cases of SCC were retrieved from the archives of Temple University Oral Pathology Laboratory as formalinfixed and paraffin-embedded tissue. There were 21 cases of SCC in the under 40 age group (14 to 40 years, age range; 33 years, average age) and 19 cases of SCC in the over 40 age group (53 to 88 years, age range; 70 years, average age). The most c o m m o n location of SCC for both age groups was the lateral tongue. LCs were immunostained for S-100 protein and H L A - D R antigen and counted as the number of positively staining cells (having at least one dendrite per cell body) per millimeter o f epithelial surface length (ESL). Results: For the over-40 age group the mean value o f S-100 positive cells was 7.77 cells/ESL and the mean value of H L A - D R positive ceils was 1.81 cellsfESL: for the under-40 age group the m e a n value of S-100 positive cells was 8.97 cells/ESL and the m e a n value of H L A - D R positive ceils was 1.99 cells/]ESL. Statistical analysis of the data (student's t test) failed to disclose a statistically significant difference between the mean values for either of the markers studied (S- 100:p = 0.55: H L A - D R : p = 0.79). Our data suggest that quantitative variations in LC numbers do not contribute significantly to differences in pathogenesis of SCC in young versus old patients. IMMUNOHISTOCHEMICAL EVALUATION OF TRANSFORMING GROWTH FACTOR BETA IN OSTEOSARCOMAS OF THE JAWS AND ITS POTENTIAL ROLE IN TUMOR PROLIFERATION. J. Tiffee, T. Aufdemorte. University of Texas Health Science Center, San Antonio. Transforming growth factor beta fTGF-13) is a cytokine with numerous functions in several different tissues. The largest source of TGF-[3 in h u m a n s is bone: TGF-[3 has been shown to stimulate bone formation via Type I collagen production and influences several other metabolically active bone proteins. Also, studies on cell cultures have shown both inhibitory and stimulatory effects of TGF-[3 on osteosarcoma cells. However, very little information is available as to the level of expression of TGF-13 in h u m a n osteosarcoma tissue. The purpose of this study was to retrospectively evaluate a series of osteosarcomas for the presence of intracellular TGF-I3. To this end, formalin-fixed paraffin-embedded tissue from four chondroblastic osteosarcomas of the jaws were retrieved
from our files. Sections were then evaluated immunohistochemically using a polyclonal antibody against TGF-I~ subtypes 1.2. and 3. This assessment revealed positive reactivity by tumor cells in all cases. However. the better differentiated tumors showed a greater number of positive ceils, so that lesions with greater differentiation possessed a greater level of intracellular TGF-13. This data would tend to support the conclusions drawn by others that further study is necessary to more thoroughly evaluate the significance of TGF-13 in both neoplastic and nonneoplastic lesions of bone. ULTRASTRUCTURAL DEMONSTRATION OF MYOF|BROBLASTIC FEATURESIN CELL CULTURE OF A CENTRAL ODONTOGENIC FIBROMA. F. Kratochvil, J. Schwartz. M. Cardinali. Naval Dental School and National Institute of Dental Research. Bethesda. Md. Myofibroblasts are considered to be responsible for tissue contraction during wound healing and the desmoplastic response to s o m e carcinomas, i.e. breast cancer. Mucosal retraction, producing a palatal mucosal cleft, is often seen with central odontogenic fibromas ~COF) of the anterior maxilla. W e searched for features of myofibroblastic differentiation in a cell culture of a COF that showed prominent palatal mucosal clefting. Ultrastructural examination by transmission electron microscopy showed arrays of intermediate filaments with focal densities. In addition, these cells demonstrated subplasmalemmal micropinocytotic vesicles, external lamina, and intercellular junctions. Demonstration of myofibroblastic features in this neoplasm m a y help explain the interesting and unique clinical feature of mucosal clefting that some of these tumors express. Also. this appears to represent the first report of a viable cell culture of a COF. OXIDANT STRESSSYNERGISM IN AIDS-KS PATHOGENESIS S Mallery, R. Bailer, C. Ng-Bautista. C. Hohl, G. Ness, G. Brierley. The Ohio State University, Columbus. Despite its recognition as the most prevalent HIV-associated neoplasm, speculation still abounds regarding the pathogenesis of AIDS-related Kaposi's sarcoma ~AIDS-KS). However, it has been established that both cytokines e.g. IL-6, and HIV-associated products e.g. Tat. are integral in AIDS-KS cellular proliferation. Further. both experimental and clinical evidence is accumulating to link reactive oxygen intermediates (ROD with both cytokine induction (via both NF-KB dependent and NF-KB independent routes) as well as the subsequent cytokine (TNFc~) stimulation of HIV replication. Features o f AIDS-KS patients, such as retention of their phagocytes, presence of sustained immunostimulation. and a frequent history of a KS lesion arising at a traumatized site. make oxidant stress a viable clinical factor in AIDS-KS development. The objective of this study was to monitor, via time course nucleotide analyses. AIDS-KS cellular bioenergetic response to physiologically relevant levels of H202. Our nucleotide profiles show that AIDS-KS cells have an inherent, statistically significant biochemical deficit, e.g. lower levels of high energy phosphates. glutathione, and NADPH, even prior to oxidant stress. Following exposure to H202, only the h u m a n microvascnlar endothelial cells (a putative KS progenitor cell) responded with beneficial bioenergetic adaptations that reflected co-ordination o f energy generating and cytoprotective pathways. Also, some o f the AIDS-KS strains retained intracellular GSSG subsequent to oxidant challenge, inviting the formation of deleterious protein mixed disulfides. Therefore institution of antioxidant therapy (low-risk/ potential high-benefit) m a y prove beneficial in preventing disease progression.