Low-dose isotretinoin versus beta-carotene to prevent oral carcinogenesis: long-term follow-up.
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Anticarcinogenic Agents↗
Biomedical subjects
J G Batsakis
Publications and source records attributed to J G Batsakis.
Chromosomal and DNA ploidy characterization of salivary gland neoplasms by combined FISH and flow cytometry.
Concurrent DNA ploidy by flow cytometry and interphase FISH analysis of chromosomes 6 through 12, 17, 18, X, and Y were prospectively performed on 22 salivary gland neoplasms (four benign and 18 malignant) to investigate the diagnostic and biological implications of their alterations in these neoplasms. Our results show that benign neoplasms lack DNA aneuploidy and numerical chromosomal abnormalities. Low-grade malignant neoplasms, except for two lesions, manifested small chromosomal gains and losses and were generally DNA diploid or near-diploid aneuploid, whereas all high-grade tumors showed marked polysomy and were DNA aneuploid. Marked intratumoral and intertumoral chromosomal heterogeneity also were noted in and between individual tumors. Although polysomy was the main finding in DNA aneuploid lesions, monosomy was more noted in DNA diploid neoplasms and was restricted to chromosomes 8, 11, and 17. Significant correlation between the DNA index, chromosomal aneusomy, histological grade, and tumor stage was noted. Our study indicates that (1) benign salivary gland neoplasms lack gross DNA content and numerical chromosomal abnormalities, (2) clonal chromosomal alterations are manifested in most DNA diploid and all DNA aneuploid malignant tumors, (3) chromosomal gain is the most common alteration; chromosomal loss is less frequent and restricted to certain chromosomes, and (4) DNA aneuploidy and chromosomal aneusomy characterize tumors with aggressive features.
Adult↗
Microsatellite alterations at chromosome 8q loci in pleomorphic adenoma.
OBJECTIVE: To determine the extent, localization, and clinical significance of microsatellite loci alterations at sites of reported cytogenetic abnormalities in pleomorphic adenomas. BACKGROUND: Pleomorphic adenoma is a benign salivary gland tumor with a propensity for recurrence and potential for malignant conversion. Although its cause remains unclear, clonal cytogenetic abnormalities have been reported consistently. DESIGN: DNA extracted from paired normal and tumor tissue specimens from 1 patient with carcinoma ex pleomorphic adenoma and 17 patients with pleomorphic adenoma (3 contained foci of carcinoma ex pleomorphic adenoma) was evaluated for loss of heterozygosity at microsatellite loci with a multiplex polymerase chain reaction-based analysis. Correlation with clinical and pathologic features was performed. RESULTS: Overall 10 (56%) of 18 cases manifested loss of heterozygosity at the loci tested. The frequency of loss of heterozygosity noted on 3p, 6q, 8p, 8q, and 12q microsatellite loci was 17%, 12%, 8%, 47%, and 27% of informative cases, respectively. Specimens from patients with carcinoma ex pleomorphic adenoma showed a similar loss of heterozygosity incidence at these loci. No apparent association between molecular abnormalities and clinical-pathologic features was observed in this cohort. CONCLUSIONS: Loss of heterozygosity at microsatellite loci on 8q, a breakpoint at which translocations have been previously documented in pleomorphic adenoma, is a frequent event in this tumor. The incidence is not increased in patients with focal carcinoma ex pleomorphic adenoma, suggesting that loss of heterozygosity at 8q is an early event in tumorigenesis. Further evaluation at these loci is needed to identify potential tumor suppressor genes that may be associated with the initiation and progression of pleomorphic adenomas.
Adenoma, Pleomorphic↗
Genotypic alterations in benign and malignant salivary gland tumors: histogenetic and clinical implications.
Loss of heterozygosity (LOH) and microsatellite instability (MI) were examined at 24 microsatellite loci in 46 primary benign and malignant salivary gland tumors. Among the 27 benign tumors, 11 (40.7%), manifested microsatellite alterations in at least one locus; of these, five (18.5%) showed LOH and four (14.8%) had microsatellite instability at two or more loci. Four of 11 pleomorphic adenomas (36.4%) had allele loss on the long arm of chromosome 8. Among the 19 malignant neoplasms examined, 10 (52.6%) and one (5.2%) had allele losses and MI, respectively, at multiple loci; three tumors showed MI at only one locus. Frequent LOH was detected at D8S166 (8q11-12), D17S799, and D17S122 (17p-17p11-2) loci, with an incidence of 40%, 37.5%, and 43%, respectively. In general, malignant neoplasms with LOH exhibited aggressive tumor characteristics. Statistically significant correlation's were found between LOH and pathologic classification (chi 2, p = 0.05), higher grade (p = 0.02), DNA aneuploidy (p = 0.005), and a proliferative index of > 6% (p = 0.005) of the malignant tumors. Carcinomas with 17p loci alterations, including two carcinomas expleomorphic adenoma with concurrent 8q LOH, showed more aggressive features. The results suggested that (a) loci on chromosome 8q may harbor a tumor suppressor gene or genes associated with the development or progression of some salivary neoplasms; (b) alterations on the short arm of chromosome 17 may represent an event related to tumor progression; and (c) tumors with LOH at multiple loci have aggressive biologic characteristics.
Adenoma↗
Intratumoral genetic heterogeneity in primary head and neck squamous carcinoma using microsatellite markers.
We investigated intratumoral genetic variability using 13 of the most frequently altered microsatellite loci in primary head and neck squamous carcinoma to determine the extent and the implication of this feature on the interpretation of the genetic analysis of these tumors. DNA extracted from four spatially different samples of 17 prospectively resected specimens, in addition to matching normal mucosa, was tested. Overall, the highest incidence of loss of heterozygosity was noted at chromosomes 3p and 9p loci (70% in each). Chromosomes 8p and 17p loci showed 35% and 40% loss of heterozygosity, respectively. Loss of heterozygosity was homogeneously manifested in all different samples of tumors with these alterations. Microsatellite instability was noted in two (17%) tumors, one of which showed intratumoral heterogeneity. Our study indicates that single sample analysis may reflect the genetic alterations in a given primary head and neck squamous carcinoma using these markers.
Adult↗
Intracellular crystalline deposits in lymphoplasmacellular disorders.
Crystalline immunoglobulin intracellular inclusions may be found in a range of B-cell neoplasias, including MALT (mucosa-associated lymphoid tissue) lymphoma. The crystals are regarded as an outcome of impaired cell secretory activity leading to their accumulation. At times the deposits may be so profound as to obscure the diagnosis and may even lead to misdiagnosis. Examples of the crystals are presented along with a brief literature review.
Aged↗
Methylation, a major mechanism of p16/CDKN2 gene inactivation in head and neck squamous carcinoma.
We studied 11 head and neck squamous carcinoma (HNSC) cell lines and 46 primary tumors for p16 gene status by protein, mRNA, and DNA genetic/epigenetic analyses to determine the incidence, the mechanism(s), and the potential biological significance of its inactivation. Of the 11 cell lines, only 1 showed intact p16 and 10 lacked its protein and mRNA; DNA analysis of these 10 cell lines showed 2 homozygous deletions, 6 methylations at exon 1 and 2, and 2 with no detectable abnormalities. In primary tumors, 16 (34.7%) of the 46 showed detectable p16 protein and mRNA; of these, 12 had no DNA abnormalities and 4 had only exon 2 methylation. Loss of p16 expression was found in three tumors with concurrent mutation at exon 2 and methylation at exon 2 (two) and both 1 and 2 (one). Of the 30 tumors that lacked p16 protein, 27 also lacked mRNA, 1 had detectable p16 mRNA, and 2 failed RT-PCR amplification. Twenty-two of the thirty tumors showed DNA alterations and eight manifested no abnormalities; DNA alterations comprised 6 homozygous deletions, 2 concurrent mutations and methylation of exon 2, and 13 with methylation at exon 1 and exons 1 and 2 (12 with methylation only and 1 with mutation) at exon 1. Except for patients' gender (P = 0.02), no significant correlation between p16 and clinicopathological factors was observed. We conclude that in HNSC 1) intragenic p16 alterations are infrequent events, 2) methylation of exon 1 constitutes a common mechanism in silencing the p16 gene, 3) p16 inactivation may play an important role in the early development and progression of HNSC, and 4) no association between p16 alterations and conventional clinicopathological factors was noted in this cohort.
Adult↗
Accumulation of p53 protein and retinoic acid receptor beta in retinoid chemoprevention.
Although retinoids have proven to be effective as chemopreventive agents in reversing premalignant oral lesions and preventing second primary tumors, their mechanisms of chemopreventive efficacy in clinical settings have not been established. To better define this mechanism, we studied p53 protein and retinoic acid receptor beta (RAR-beta) expression in 52 baseline biopsy samples taken from premalignant oral lesions. We then studied p53 expression in 39 matched samples and RAR-beta expression in 38 matched samples before and after treating them with isotretinoin. The study results were then compared with clinical responses. To detect p53 protein expression, 4-micrometer sections of formalin-fixed, paraffin-embedded tissue specimens were used for immunohistochemical analysis with a monoclonal anti-p53 antibody, and levels of p53 expression were recorded with a labeling index (LI). Expression of RAR-beta mRNA was determined using nonradioactive in situ hybridization, and the staining intensity of RAR-beta mRNA was semiquantitated using scores from 0 (no expression) to 3+ (highest expression). p53 protein was detected in 85% of all lesions. High p53 protein expression (LI >/= 0.2) was detected in 25% of the lesions at baseline and in 18% of the lesions after isotretinoin therapy. The clinical response was 65% for lesions having low p53 expression (LI < 0.2) and 27% for lesions having high p53 expression (P = 0.027). Expression of RAR-beta mRNA was detected in 40% of the patients at baseline and increased to 90% of the patients after isotretinoin therapy (P < 0. 001). Seventy-two percent of the patients having low p53 expression had no RAR-betamRNA expression at baseline, whereas 22% of the patients having high p53 expression had no RAR-beta expression, which suggests that patients having low p53 expression tended to lose RAR-beta mRNA expression in their tissues. Eighty-three percent of patients having low p53 expression had up-regulation of RAR-beta mRNA after isotretinoin therapy, compared with 22% of patients with high p53 expression (P = 0.003). We correlated baseline p53 protein expression with RAR-beta modulation and clinical responses to isotretinoin therapy. The patients with low p53 protein expression at baseline and up-regulation of RAR-beta after isotretinoin therapy achieved a 70% rate of major response. The patients with low p53 protein expression and either no change or down-regulation of RAR-beta or with high p53 expression and up-regulation of RAR-beta had a response rate of 50%. The patients with high p53 protein expression and either no change or down-regulation of RAR-beta had a response rate of only 14% to isotretinoin therapy. The basic mechanisms underlying the association between clinical responses and these two biomarkers need to be explored.
Adult↗
Genotypic characterization of a primary mucoepidermoid carcinoma of the parotid gland by cytogenetic, fluorescence in situ hybridization, and DNA ploidy analysis.
We present a case of mucoepidermoid carcinoma with t(3;12)(q24;p13) and polysomy X by cytogenetic and fluorescence in situ hybridization (FISH) techniques. Flow cytometric DNA analysis of the primary tumor showed DNA aneuploidy and analysis of cultured tumor cells showed DNA diploidy indicating restricted growth of the diploid tumor cells in short-term tissue culture. Interphase cytogenetic analysis of chromosomes 1, 3, 6-12, 16-18, and X in the primary tumor showed polysomy 1, 9, 18, and X, monosomy 8 and 17, and disomy 3, 6, 7, 10-12, and 16. Except for chromosome X, other numerical chromosomal abnormalities were not detected by conventional cytogenetic analysis. Our combined approach allowed for better characterization of the genotypic features of this neoplasm.
Aged↗
A mucoepidermoid carcinoma of minor salivary gland with t(11;19)(q21;p13.1) as the only karyotypic abnormality.
We present the cytogenetic analysis of a mucoepidermoid carcinoma of the minor salivary gland with t(11,19)(q21;p13.1) as the sole karyotypic abnormality. Our findings, along with those of previous reports, indicate that this translocation is an early and most likely a primary event in the development of a least a subset of these neoplasms.
Adolescent↗
Prognostic significance of biomarkers (c-erbB-2, p53, proliferating cell nuclear antigen, and DNA content) in salivary duct carcinoma.
Salivary duct carcinoma (SDC), a rare neoplasm of the major salivary glands, is a high-grade carcinoma with a predilection for elderly men. The authors investigated the prognostic role of p53, c-erbB2, proliferating cell nuclear antigen (PCNA), and DNA flow cytometry in a pathobiological evaluation of a cohort of 30 patients with these neoplasms. The patient group comprised 24 men and 6 women, with ages ranging from 22 to 87 years (mean = 61 years). Twenty-eight tumors were located in the parotid gland and two in the submandibular gland. Tumor size ranged from 1.0 to 8.0 cm (mean = 3.48 cm). Regional metastases were found in 73.3% (22 patients), systemic metastases in 43.3% (13 patients), and recurrences in 8 (26.6%) patients. DNA aneuploidy was found in 18 tumors (58.0%) and DNA diploidy in 12 (42%), with proliferative fractions ranging from 8.60% to 15.5 (mean = 10.6%). p53 protein nuclear immunostaining was positive in 56.6% and c-erbB2 overexpression was observed in 63% of the tumors. PCNA positivity ranged from 16.5% to 91.0%, with a mean of 49.5%. p53 immunopositivity, DNA aneuploidy, high growth, and proliferative fractions by PCNA and flow cytometry did not correlate with patient outcome. These results indicate that tumor size (P = .05), distant metastasis (P = .006), and C-erbB2 amplification (P = .04) are independent prognostic parameters in patients with salivary duct carcinoma.
Adult↗
Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment.
To better understand genetic alterations in oral premalignant lesions, we examined 84 oral leukoplakia samples from 37 patients who had been enrolled in a chemoprevention trial. The samples were analyzed for two microsatellite markers located at chromosomes 9p21 and 3p14. Loss of heterozygosity (LOH) at either or both loci was identified in 19 of the 37 (51%) patients. Of these 19 patients, seven (37%) have developed head and neck squamous cell carcinoma (HNSCC) while only one of 18 (6%) of patients without LOH developed HNSCC. Our data suggest that clonal genetic alterations are common in oral premalignant lesions; that multiple genetic alterations have already occurred in oral premalignant lesions, allowing at least a focal clonal expansion; and that losses of the 9p21 and 3p14 regions may be related to early processes of tumorigenesis in HNSCC. These genetic alterations in premalignant tissues may serve as markers for cancer risk assessment.
Adult↗
Genotypic analysis of primary head and neck squamous carcinoma by combined fluorescence in situ hybridization and DNA flow cytometry.
Concurrent DNA flow cytometric (FCM) and fluorescence in situ hybridization (FISH) analyses were prospectively performed on 24 primary untreated head and neck squamous carcinomas for characterization of the genotypic and phenotypic DNA aberrations of these neoplasms. Eleven tumors (42.0%) manifested DNA diploidy (DI = 1.00) and 15 (58.0%) had DNA aneuploidy (DI < or > 1.00) by FCM. Fluorescence in situ hybridization results showed aneusomy in the majority of DNA diploid and in all DNA aneuploid tumors. The extent of the abnormalities for individual chromosomes and the number of involved chromosomes in a given DNA diploid or aneuploid tumor were significantly different. Overall, a statistical correlation between the FCM DNA index (DI) and the magnitude of the chromosomal aberration by FISH was found. Our results also show a significant association between the DI and histologic differentiation and stage of disease in these neoplasms. In conclusion, (1) chromosomal aneusomy characterizes most DNA diploid (DI = 1.00) and all DNA aneuploid (DI < or > 1.00) head and neck squamous carcinomas; (2) polysomy is the most prevalent finding; (3) loss of the Y chromosome in tumors from male patients is a consistent feature; (4) the FCM DI reflects net chromosomal gains or losses in these neoplasms; and (5) DNA aneuploidy is associated with tumor aggressiveness.
Adult↗
Orofacial granulomatosis and Crohn's disease.
Orofacial granulomatosis is a clinical entity of either unknown or specific causation. Specific causes include sarcoidosis, chronic infective granulomas, and Crohn's disease. The remainder of cases are idiopathic, but the clinical presentations of orofacial swellings and intraoral mucosal lesions are similar. So, too, are the histopathologic findings of noncaseating granulomas, edema, and chronic lymphoproliferative infiltrate. Crohn's disease is not responsible for all forms of orofacial granulomatosis, but the orofacial manifestations of the disease may herald its diagnosis.
Crohn Disease↗
Cystic fibrosis and the sinonasal tract.
Cystic fibrosis is considered to be one of the most common fatal inherited diseases. Sinonasal manifestations are not outstanding as compared with those in the lower respiratory tract. Panopacification of the paranasal sinuses is, however, almost universal on radiologic examination of patients, although many of these patients do not have sinonasal symptoms. Approximately 10% to 20% of cystic fibrosis patients will eventually require surgical treatment of their sinuses. All treatment, including surgery, is transiently effective; none is curative.
Adolescent↗
Don't confuse dental soft tissues with odontogenic tumors.
Surgical pathologists are cautioned against the misinterpretation of immature dental tissues (dental papillae and follicles) and dental pulp as odontogenic tumors, especially odontogenic myxomas and fibromas. The close histologic similarity of the immature tissues to tumors may require a clinical-radiologic correlation with the histopathologic specimen in order to distinguish the locally aggressive tumors from innocuous dental tissues.
Dental Papilla↗
Pharyngeal hypophysis.
Derived from embryologic remnants of Rathke's pouch and its craniopharyngeal duct, the pharyngeal hypophysis has long been considered to be present in all humans. This thesis has been recently challenged, but the weight of investigative evidence still favors the original premise. The pharyngeal hypophysis is just one product of Rathke's pouch. Others are extracranial pituitary tumors, the very rare craniopharyngioma, pharyngeal hypopharyngeal cysts, and cerebrospinal fluid rhinorrhea.
Craniopharyngioma↗
Ewing's sarcoma and peripheral primitive neuroectodermal tumor: an interim report.
The primitive neuroectoderm and its progeny seemingly give rise to an ever-increasing number of clinicopathologic entities. Ewing's sarcoma and peripheral primitive neuroectodermal tumor have recently been united by relatively unique antigens expressed by the MIC-2 gene, commonly coexpressed neural markers, and cytogenetic and molecular genetic abnormalities. Because of these factors, the current thinking is that Ewing's sarcoma and the peripheral primitive neuroectodermal tumor are parts of a phenotypic spectrum. We present an "interim report" on this group of neoplasms, emphasizing their presentation in the head and neck.
Female↗