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Biomedical subjects

M A Luna

Publications and source records attributed to M A Luna.

At least 37 records · Page 2Linked to original sources
PubMed1998

Genetic alterations in acinic cell carcinoma of the parotid gland determined by microsatellite analysis.

We investigated, for the first time, the genetic alterations at certain chromosomal loci in 25 primary parotid acinic cell carcinomas to define the most frequently altered chromosomal regions and their association with pathologic features and DNA content analysis. Our results showed that 21 (84.0%) of the tumors had alteration in at least one of the loci tested. In general, chromosomal regions at chromosomes 4p, 5q, 6p, and 17p were more frequently altered than those on chromosomes 1p and 1q, 4q, 5p, and 6q. Certain markers at 4p15-16, 6p25-qter, and 17p11 regions showed the highest incidence of LOH, suggesting the presence of tumor suppressor genes associated with the oncogenesis of these tumors. LOH was significantly associated only with tumor grade. No apparent correlation between LOH and other clinicopathologic and DNA content characteristics was identified. Our study broadly defined the chromosomal arms and loci that may be targeted for further localization of the minimally deleted regions involved in the tumorigenesis of these tumors.

Adult↗
PubMed1998

Histologic evaluation of neck dissection specimens.

Histologic evaluations of neck dissection specimens from carcinomas of the head and neck provide information required for disease staging, planning further treatment, and prognosis. Histologic evaluation performed adequately and accurately can and continues to provide a more accurate, meaningful, and promising means of formulating and predicting prognosis including risk of metastases. A multi-institutional study using comprehensive standardized histologic evaluation of histopathologic variables of primary tumor and cervical lymph nodes among homogenous patient groups receiving similar therapy is important. Histopathologic parameters remain an important adjunct parameter to clinical evaluation in guiding, planning treatment, and predicting prognosis for patients with head and neck cancers.

Carcinoma↗
PubMed1998

Palatal canalicular adenoma: report of 12 cases and review of the literature.

Canalicular adenoma is the second most common type of adenoma of the oral region and arises almost exclusively in the upper lip. Other locations include the buccal mucosa, the palate, and the parotid gland. We report 12 cases of canalicular adenoma that arose in the palates of nine women and three men between the ages of 42 and 76 years. The tumor presented as a nonulcerated (eight patients) or ulcerated (four patients) lesion, usually at the junction of the hard and soft palates. Two tumors were misdiagnosed: one as adenoid cystic carcinoma and the other as low-grade adenocarcinoma. Both patients had had partial maxillectomy; the patient diagnosed with adenoid cystic carcinoma also received radiotherapy. One patient reported having had an adenoma removed from the palate 10 years previous to presentation; thus, the tumor was classified as a recurrence. Evidence of tumor metastasis was absent in all cases during the follow-up period, which ranged from 1 to 25 years. Eleven patients are alive and disease free; one died of other causes. Canalicular adenoma does not commonly occur in the palate. This tumor has an excellent prognosis after conservative surgical treatment in all locations. Pathologists should be aware of the occurrence of this neoplasm in the palatal region and of its histopathology so they can distinguish it from malignant tumors of the salivary gland.

Adenoma↗
PubMed1998

Genotypic analysis of flow-sorted and microdissected head and neck squamous lesions by whole-genome amplification.

To investigate the utility of primer extension preamplification (PEP) in the genetic analysis of head and neck squamous tumorigenesis, microsatellite analysis was performed on matched deoxyribonucleic acid (DNA) samples extracted from 32 flow-sorted and microdissected specimens before and after PEP. Eighteen fresh and nine archival specimens were taken from invasive carcinomas, and five specimens were obtained from microdissected archival premalignant squamous epithelial lesions. Identical microsatellite patterns were observed in 276 (87%) of the 319 paired PEP and non-PEP genotypes with sufficient DNA. Overall, 13 (4%) of the PEP and 28 (8.8%) of the non-PEP fresh tissue samples failed specific microsatellite amplification. All 14 PEP-archival specimens were successfully amplified. Sorted cells showed a higher incidence (42.8%) of loss of heterozygosity (LOH) in both PEP and non-PEP samples compared with their unsorted counterparts. The results of this study indicate that (a) PEP is a simple and reliable technique for enhancing the DNA yield from small specimens; (b) flow sorting, in certain cases, improves the interpretation of genetic results; and (c) PEP may be used to compensate for PCR failure of unamplified DNA specimens in these lesions.

Carcinoma, Squamous Cell↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

Soft tissue sarcoma of the head and neck in children and adolescents.

BACKGROUND: The experience of one institution in treating soft tissue sarcomas of the head and neck in a pediatric population is presented. METHODS: Case materials of 134 patients younger than 20 years who were referred to the University of Texas M. D. Anderson Cancer Center between 1970 and 1989 for treatment of sarcoma of the head and neck were retrospectively reviewed. Patients with rhabdomyosarcoma underwent multimodality treatment consisting of surgery, irradiation, and chemotherapy. Wide resection was the treatment used for patients with nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS). Adjuvant chemotherapy and irradiation were used to treat high grade neoplasms and residual disease. The clinical response to therapy was measured in terms of the disease-specific survival rate. RESULTS: Seventy-nine of 134 patients presented with untreated or biopsy-proven disease. Fifty-six had rhabdomyosarcoma and 23 had NRSTS: At 2 and 5 years, the disease-specific survival rates for patients with rhabdomyosarcoma were 74% and 63%, respectively, and patients with NRSTS had 80% and 75% disease-specific survival rates at 2 and 5 years, respectively. CONCLUSIONS: Rhabdomyosarcoma of the head and neck in children is effectively treated with multimodality therapy. Prognostic indicators for rhabdomyosarcoma include completeness of tumor resection and the development of recurrent disease. Aggressive surgical resection is the treatment of choice for patients with NRSTS: Prognostic indicators for NRSTS include completeness of tumor resection and the development of recurrent disease.

Adolescent↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Cytomegalovirus pneumonia in adult nontransplantation patients with cancer: review of 20 cases occurring from 1964 through 1990.

The objectives of this study were to estimate the frequency of cytomegalovirus (CMV) pneumonia and describe its clinical and radiological presentation in adult nontransplantation patients with cancer. Of the 10,441 autopsies performed at M. D. Anderson Cancer Center (Houston) during the period of January 1964 through December 1990, 9,029 were evaluable. Twenty histopathologically confirmed cases of CMV pneumonia were found, representing a frequency of 2.2 cases per 1,000 autopsies. When the frequency of CMV pneumonia was compared for the periods 1964-1979 (1.5 cases per 1,000 autopsies) and 1980-1990 (4.6 cases per 1,000 autopsies), a statistically significant increase due to an increase in the number of patients with solid malignancies was observed (P < .05). CMV pneumonia is an uncommon diagnosis at autopsy for adult nontransplantation patients with cancer and is usually found in conjunction with a disseminated neoplastic process.

Adult↗
PubMed1996

Thyroid gland ectopias.

Failures of descent of the medial anlage of the thyroid and incomplete obliteration of its vertical tract lead to midline or near-midline ectopias such as lingual thyroid and thyroglossal cysts. Each poses special diagnostic and therapeutic considerations. "Ectopias" of the thyroid gland lateral to the carotid artery and jugular vein, however, cannot be readily explained by current embryological information. In these instances, and especially for intranodal thyroid tissue, a metastasis from an occult thyroid primary is the mandatory first consideration.

Carcinoma, Papillary↗
PubMed1996

Microsatellite instability in preinvasive and invasive head and neck squamous carcinoma.

To investigate the extent and significance of microsatellite instability in head and neck carcinogenesis we analyzed DNA extracted from normal squamous epithelium, severe dysplasia, and corresponding carcinoma specimens from 20 patients by multiplex polymerase chain reaction. Loci on chromosomes 3p, 5p, 5q, 8p, 9p, 9q, 11q, 17p, 17q, 18p, 18q were selected for analysis. Our results show that three of the dysplasias (15.0%) and six of the invasive carcinoma (30.0%) manifested instability at multiple loci. Two of the dysplastic lesions had identical alterations in the corresponding carcinomas and one showed instability differences in only two of eight loci. Normal squamous epithelium lacked microsatellite instability. No apparent association between smoking, alcohol use, or family history of cancer and instability was found in this small cohort. Invasive carcinomas with instability were relatively more poorly differentiated and had a higher stage and a high proliferative fraction. Our study indicates that microsatellite instability is 1) noted in a small subset of dysplastic lesions of head and neck squamous epithelium and 2) present in approximately one-third of invasive lesions, usually with aggressive characteristics, and may clinically be a late event associated with tumor progression.

Aged↗
PubMed1996

Allelic loss and replication errors at microsatellite loci on chromosome 11p in head and neck squamous carcinoma: association with aggressive biological features.

The frequent loss of heterozygosity (LOH) demonstrated at chromosome 11p regions in several sporadic malignancies has suggested the presence of tumor suppressor genes at these locations. To obtain detailed mapped incidence of the microsatellite alterations at these regions and to investigate the possible correlation between the genotype and the pathobiological characteristics of head and neck squamous carcinoma, we analyzed paired DNA samples from normal mucosa and primary tumor specimens from 56 patients with these tumors. Our results show that 50.9% of the tumors had microsatellite alterations at one or more of these loci. LOH was manifested in 45. 5% and instability in 5.5% of the tumors. 11p15 loci showed more frequent LOH (39.6%) than those of 11p13 (29.3%) and 11p11-12 (18. 8%); the D11S988 (11p15) marker showed the highest single locus incidence of LOH (29.7%). Eight tumors (22.2%) demonstrated simultaneous LOH at both the 11p15 and 11p13 regions. LOH was significantly associated with poor histological differentiation, DNA aneuploidy, and high proliferative activity in these neoplasms. Our study extends the involvement of the 11p13 and 11p15 regions to head and neck squamous tumorigenesis and indicates that the terminal loci of 11p may harbor a tumor suppressor gene(s) associated with the progression of these tumors.

Adult↗
PubMed1995

Sequential p53 mutation analysis of pre-invasive and invasive head and neck squamous carcinoma.

Single-stranded conformational polymorphism (SSCP) and direct sequencing were performed on uninvolved mucosa, severe dysplasia and invasive carcinoma samples from 20 patients with head and neck squamous carcinoma. Seven (35%) of the non-invasive lesions and 15 (75%) of the invasive carcinomas manifested p53 mutations. Although the majority of mutations were mis-sense, resulting in single amino acid substitution, a silent mutation encoding for the same amino acid and 2 non-sense mutations encoding a stop codon were also observed. Mutations in invasive carcinoma were mostly in exon 8 and involved codons 296, 288 and 298; non-invasive lesions showed more mutations at exons 5 to 7. Five lesions showed simultaneous mutations in 2 different exons; in 3 both non-invasive and invasive carcinomas showed primary mutation at exons 5 to 7, and invasive carcinoma showed a secondary mutation at exon 8. Different codon mutations in the same exon between dysplastic and the corresponding carcinoma samples were found in 2 cases. p53 alterations were not observed in any of the normal mucosa samples. No apparent association between p53 mutations and conventional clinicopathologic parameters, including DNA content, was found in this cohort. Our study indicates that (i) p53 alteration is an early event in the genesis of a subset of head and neck squamous carcinomas, (ii) normal mucosa within the resected specimens lacked p53 mutation, (iii) sequential mutations of different exons of the p53 gene suggests accumulation of genetic alterations during the neoplastic transformation of these lesions and (iv) the difference in codon mutation of the same exon between dysplastic and corresponding carcinoma suggests an independent clonal development.

Adult↗
PubMed1995

Sequential loss of heterozygosity at microsatellite motifs in preinvasive and invasive head and neck squamous carcinoma.

Studies of sequential molecular alterations in noninvasive and invasive head and neck squamous carcinoma are few in number. Consequently, the genetic changes associated with the neoplastic transformation of these carcinomas have not been defined. To identify chromosomal alterations in preinvasive and invasive head and neck squamous carcinoma, we analyzed DNA from microdissected normal squamous epithelium, severe dysplasia, and invasive carcinoma samples from 20 patients for loss of heterozygosity (LOH) at microsatellite loci by multiplex PCR. Twenty-five microsatellite repeats on chromosomes 3p, 5q, 8p, 9p and 9q, 11q, 17p, 17q, and 18p and 18q regions were used. In informative cases, LOH in noninvasive lesions was observed in 9p (28%), 9q and 18q (10%), 11q and 17p (7%), and 3p and 18p (5%). A high incidence of LOH in invasive carcinoma was observed at 9p (72%), 8p (53%), 3p (47%), 9q (35%), and 11q (33%). LOH was also associated with DNA aneuploidy, high tumor stage, and poor histological differentiation. Our results indicate that: (a) the high incidence of LOH at loci on chromosomes 9p, 8p, 3p, 9q, and 11q implicate these regions in head and neck squamous carcinoma tumorigenesis; (b) 9p loci alterations are manifested in the early development of these tumors; (c) LOH is correlated with poor prognostic clinicopathological factors; and (d) LOH at 8p loci appears to be associated with the tumor's aggressive features.

Adult↗