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PubMed2003

Primary primitive peripheral neuroectodermal tumor of the prostate. Immunophenotypic and molecular study of a case.

A case of primitive peripheral neuroectodermal tumor arising in the prostate gland of a 31-year-old man and first diagnosed through a biopsy is reported. Microscopically, the tumor was made up of solid nests and sheets of small round cells, and it was difficult to distinguish the neoplasm from other small round cell tumors, such as small cell carcinoma, rhabdomyosarcoma, or malignant lymphoma. Immunohistochemically, the tumor cells showed immunoreactivity for CD99, vimentin, neuron-specific enolase, and synaptophysin. The neoplasm was excised by a radical surgical procedure preceded by chemotherapy and radiation therapy. The morphologic diagnosis of the prostatectomy specimen was complemented by molecular analysis performed on viable microdissected tissue obtained from formalin-fixed, paraffin-embedded tumor sections. Polymerase chain reaction and sequencing assessment showed the presence of EWS/FLI1 type 2 chimeric transcript, confirming the diagnosis of peripheral primitive neuroectodermal tumor. To our knowledge, this is the first description of a primary peripheral primitive neuroectodermal tumor in the prostate gland.

Adult↗
PubMed2006

Gene rearrangement and comparative genomic hybridization studies of classic Hodgkin lymphoma expressing T-cell antigens.

CONTEXT: Reed-Sternberg cells in classic Hodgkin lymphoma are enigmatic and difficult to study because they are so sparse. Tissue microdissection allows for the isolation of single Reed-Sternberg cells. Isolated Reed-Sternberg cells show clonal immunoglobulin gene rearrangement indicating a B-cell origin. Rarely, Reed-Sternberg cells in classic Hodgkin lymphoma express T-cell antigens, suggesting a possible T-cell origin. OBJECTIVE: To determine whether there is a difference in genotype between classic Hodgkin lymphoma and classic Hodgkin lymphoma expressing T-cell antigens and to document T-cell clonality. DESIGN: We studied 4 cases of Hodgkin lymphoma with a characteristic phenotype and immunoreactivity for CD2 and CD3. Single CD30+ Reed-Sternberg cells from each case were isolated by laser capture microdissection for immunoglobulin heavy chain and T-cell receptor-gamma genes by polymerase chain reaction studies. Comparative genomic hybridization was performed in all cases. RESULTS: Two of 4 cases showed clonal rearrangement of the T-cell receptor-gamma; none showed immunoglobulin heavy chain rearrangement. Two control cases were negative for T cell receptor-gamma but 1 showed immunoglobulin heavy chain rearrangement. Comparative genomic hybridization analysis revealed significant overlap in genomic alteration in Hodgkin lymphoma cases regardless of genotype or phenotype and several regions of imbalance specific to CD3+ Hodgkin lymphoma cases. All patients are alive with no evidence of disease from 10 to 44 months. CONCLUSIONS: Our findings suggest that a T-cell phenotype classic Hodgkin lymphoma can be supported by genotypic studies and that there may be cytogenetic differences between classic Hodgkin lymphoma and Hodgkin lymphoma expressing T-cell antigens.

Adolescent↗
PubMed1998

Molecular alterations in bladder cancer.

The molecular genetic changes reported in bladder tumours can be classified as primary and secondary aberrations. Primary molecular alterations may be defined as those directly related to the genesis of cancer. These are frequently found as the sole abnormality and often associated with particular tumours. We describe primary abnormalities as having a dual nature: those events involved in the production of low grade/well differentiated neoplasms, which would destabilise cellular proliferation but have minimal or no effects on cellular "social" interactions or differentiation or on rate of cell death or apoptosis; and others leading to high grade/poorly differentiated tumours, which would disrupt growth control, including cell cycle and apoptosis regulation and have a major impact on cellular differentiation. There is evidence that a target site(s) for a primary event(s) in low grade papillary superficial bladder tumours may reside on chromosome 9. However, a candidate for the initiation of high grade, flat carcinoma in situ lesions has not been yet elucidated. Novel approaches utilizing tissue microdissection techniques and molecular genetic assays are needed to shed light on this subject. Secondary genetic or epigenetic abnormalities may be fortuitous or may determine the biological behaviour of the tumour. Multiple molecular abnormalities are identified in most human cancers studied, including bladder neoplasms. The accumulation, rather than the order, of these genetic alterations is the critical factor that grants synergetic activity. In this regard, it is noteworthy that most of the altered genes act upon the two recognized critical growth and senescence pathways, TP53 and RB. There is a major requirement for well designed, randomized, prospective trials evaluating the strongest candidate markers in order to validate many reported exploratory studies. Although great enthusiasm exists with the application of various tumour makers in the management of bladder cancer, concrete clinical recommendations must be tempered at this time. As with preneoplastic conditions, the discrepancies that exist between clinical investigators regarding the significance of identifying such morphological changes have imposed crucial limitations. Another drawback has been the confusing nomenclature utilized and the lack of reproducibility in interpretation of morphological criteria. Molecular analyses utilizing well characterized preneoplastic lesions, including dysplasia samples, need to be pursued. This in turn may provide the needed information to realise the clinical relevance of detecting genetic instability, as well as molecular or epigenetic alterations, in otherwise morphologically normal appearing urothelium and preneoplastic lesions. The need now is to translate the newly developed scientific information into diagnostic and prognostic strategies, which in turn will prolong patient survival and quality of life.

Apoptosis↗
PubMed1999

Classification of small cell lung cancer and pulmonary carcinoid by gene expression profiles.

Small cell lung cancer is a common type of lung cancer that is generally classified within the spectrum of neuroendocrine lung neoplasms. Using high-density cDNA arrays, we profiled gene expression of small cell lung cancers and compared these expression profiles to those of normal bronchial epithelial cells and pulmonary carcinoids, which are classified as benign neuroendocrine tumors. We found the overall expression profiles of two small cell lung cancer cell lines, two microdissected tissue samples of primary small cell lung cancer, and cultured bronchial epithelial cells to be relatively similar to one another, with an average Pearson correlation coefficient for these comparisons of 0.63. However, we found the expression profiles of small cell lung cancers (and bronchial epithelial cells) to be surprisingly dissimilar to those of two samples of pulmonary carcinoid tumors, with an average correlation coefficient for these comparisons of 0.20. We then compared the pulmonary carcinoid expression profiles to those of two samples of infiltrating astrocytic brain cancers (oligodendroglioma and high-grade astrocytoma) and found similarity of gene expression among these four samples (average correlation coefficient, 0.57). These gene expression profiles suggest that small cell lung cancers are closely related to (and possibly derived from) epithelial cells, and that pulmonary carcinoids are related to neural crest-derived brain tumors. More generally, our results suggest that broad profiles of gene expression may reveal similarities and differences between tumors that are not apparent by traditional morphological criteria.

Carcinoid Tumor↗
PubMed1999

[Inactivation of tumor suppressor genes in uterine cervix carcinogenesis].

The importance of inactivation of tumor suppressor genes in the development/progression of carcinomas of the uterine cervix is reviewed. It is well known that HPV-related oncogenes are strongly linked to cervical cancer. However, fewer studies have explored the occurrence of inactivation of tumor suppressor genes in this neoplasia. Genetic deletions affecting tumor suppressor genes are the most common mechanism of inactivation of these genes. Studies using conventional molecular techniques such as restriction fragment length polymorphism (RFLP) and Southern Blot showed low frequency of deletions in cervical carcinomas. Detection of deletions by using RFLP and Southern Blot presents several disadvantages, the most important being the difficulty in analyzing pure tumor cells. More sensitive approaches include tissue microdissection and PCR analysis of micro-satellites. Using these approaches, it has been shown that genetic deletions are, in fact, frequent events in cervical cancers, being detected in up to 95% of the cases. Multiple genetic loci are involved, including chromosomes 3p, 5p, 6p and 11q. Deletions are detected even in precursor lesions (cervical intraepithelial neoplasia, CIN). Some deletions have been correlated with prognostic parameters, such as stage, depth of invasion, and vascular space involvement. It is concluded that cervical carcinogenesis, like in other tumors, is a multistep process, characterized by the accumulation of events including activation of oncogenes, as well as inactivation of tumor suppressor genes.

Female↗
PubMed2000

Deletion at 13q21 is associated with aggressive prostate cancers.

Previous cytogenetic and molecular genetic analyses suggest that the q21 band of chromosome 13 harbors a tumor suppressor gene(s) involved in prostatic carcinogenesis. The precise genetic location, however, has not been defined. In this study, we examined prostate cancer specimens and cell lines/xenograft for genetic deletions at 13q21, using the methods of tissue microdissection and duplex PCR. Deletions at 13q21 were detected in 13 of 147 (9%) prostate cancer samples. Deletion of the same region was also detected in the LNCaP cell line and the PC-82 xenograft of prostate cancer. The overlapping region of deletion in LNCaP and PC-82 spans 3.1 cM or 2.9 cR, which is equivalent to 1-3 Mb. The endothelin receptor B gene, a possible tumor suppressor gene at 13q21, was not located in the region of deletion. Among the 13 prostate neoplasms with deletion at 13q21, 5 were metastases, and 7 were poorly differentiated primary tumors. The only primary tumor that was not poorly differentiated but had deletion occurred in one of the youngest patients (49 years) at diagnosis. These results provide evidence that 13q21 may harbor an unidentified gene(s) whose inactivation occurs in some aggressive carcinomas of the prostate. In addition, this study provides a framework for the cloning and identification of the 13q21 gene(s).

Aged↗
PubMed2000

Somatic mutation of PTEN in vulvar cancer.

PTEN, a candidate tumor suppressor gene located at chromosome 10q23.3, has been shown to be mutated in approximately 40% of endometrial cancers. Such mutations have also been identified in endometrial hyperplasia, indicating that inactivation of the PTEN tumor suppressor gene is an early event in the genesis of some endometrial cancers. In this study, we have extended the analysis of PTEN in gynecological cancer to include adenocarcinoma of the cervix and vulvar carcinomas. Microdissected tissue (including normal tissues), preneoplastic, and neoplastic lesions were analyzed from 9 patients with cervical cancer and 10 patients with vulvar cancer. Only 1 cervical adenocarcinoma displayed a PTEN mutation. In contrast, five of eight vulvar carcinomas studied harbored PTEN mutations. Alterations were identified in carcinoma in situ as well as squamous cell carcinoma of the vulva. In two patients, PTEN mutations were identified in mucosal regions with mild or focal dysplasia. These results suggest that PTEN is frequently altered in vulvar carcinomas and can be found associated with early dysplastic changes in vulvar mucosa.

Adenocarcinoma↗
PubMed2000

The evolution of loss of heterozygosity on chromosome 17 during the progression to barrett's adenocarcinoma involves a unique combination of target sites in individual specimens.

We have previously identified thirteen common minimally deleted regions (MRs) on chromosome 17 in twelve Barrett's esophageal adenocarcinoma (BOA) specimens using 41 precisely mapped microsatellite markers (Dunn et al., Oncogene, 17: 987-993, 1999). The aim of the present study has been to identify the earliest sites of loss on this chromosome that arise and persist during the progression to BOA. This has been undertaken by the analysis of multiple carefully microdissected tissue samples from each of five esophagectomy specimens, several of which contained identifiable premalignant tissue. Our data demonstrate a stepwise accumulation of loss in each analyzed specimen, consistent with a single clonal pathway in four specimens and several coexisting pathways in one specimen. Several clonal anomalies (loss preceding heterozygosity and variable intrasample degrees of loss at different markers) were also observed. Within extensively deleted regions of the tumor (seen in three specimens), small deletions were detected in premalignant tissue, predominantly at the site of our identified MRs, and these losses were seen to expand and merge during the progression to BOA. Clonal losses at MRs were first detected in tissue showing early changes histologically, including Barrett's intestinal metaplasia and intermediate-grade dysplasia. Our results provide further support for many of the MRs we have previously identified, thereby adding to evidence for the existence of multiple novel cancer-associated genes on chromosome 17 involved in the development of BOA.

Adenocarcinoma↗
PubMed2000

Somatic von Hippel-Lindau gene mutations detected in sporadic endolymphatic sac tumors.

Endolymphatic sac tumors (ELSTs) occur sporadically or in association with an autosomal dominantly inherited tumor syndrome, von Hippel-Lindau (VHL) disease. In VHL disease, a germline mutation of the VHL tumor suppressor gene is inherited, and loss of function of the wild-type allele occurs through genetic deletion with subsequent development of neoplastic growth. Genetic alterations associated with sporadic ELSTs are less well understood. In this study, we used tissue microdissection to selectively analyze neoplastic cells from four sporadic ELSTs. In two cases, we detected somatic mutations involving VHL gene exons 1 and 2, respectively. Additionally, one of these cases revealed deletion of the VHL gene locus. Two cases did not reveal VHL gene mutation; one of these two cases showed VHL gene deletion. These results suggest that mutations and allelic deletions of the VHL tumor suppressor gene play a role in the tumorigenesis of sporadic ELSTs.

Adult↗
PubMed2001

Loss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals factors that influence delineation of candidate regions.

Loss of heterozygosity (LOH) at the long arm of chromosome 16 occurs in at least half of all breast tumors and is considered to target one or more tumor suppressor genes. Despite extensive studies by us and by others, a clear consensus of the boundaries of the smallest region of overlap (SRO) could not be identified. To find more solid evidence for SROs, we tested a large series of 712 breast tumors for LOH at 16q using a dense map of polymorphic markers. Strict criteria for LOH and retention were applied, and results that did not meet these criteria were excluded from the analysis. We compared LOH results obtained from samples with different DNA isolation methods, ie., from microdissected tissue versus total tissue blocks. In the latter group, 16% of the cases were excluded because of noninterpretable LOH results. The selection of polymorphic markers is clearly influencing the LOH pattern because a chromosomal region seems more frequently involved in LOH when many markers from this region are used. The LOH detection method, i.e., radioactive versus fluorescence detection, has no marked effect on the results. Increasing the threshold window for retention of heterozygosity resulted in significantly more cases with complex LOH, i.e., several alternating regions of loss and retention, than seen in tumors with a small window for retention. Tumors with complex LOH do not provide evidence for clear-cut SROs that are repeatedly found in other samples. On disregarding these complex cases, we could identify three different SROs, two at band 16q24.3 and one at 16q22.1. In all three tumor series, we found cases with single LOH regions that designated the distal region at 16q24.3 and the region at 16q22.1. Comparing histological data on these tumors did not result in the identification of a particular subtype with LOH at 16q or a specific region involved in LOH. Only the rare mucinous tumors had no 16q LOH at all. Furthermore, a positive estrogen content is prevalent in tumors with 16q LOH, but not in tumors with LOH at 16q24.3 only.

Breast Neoplasms↗
PubMed2001

Mutations of PTEN/MMAC1 in primary prostate cancers from Chinese patients.

PTEN/MMAC1 is a putative tumor suppressor gene located on 10q23, one of the most frequently deleted chromosomal regions in human prostate cancer. Although mutations of PTEN have often been detected in metastases of prostate cancer, localized tumors have shown lower rates of mutation, which have varied from 0 to 20% among different studies. It is unknown whether the rate of PTEN mutations is different in prostate cancer from Asian men compared with Western men. To further clarify the role of PTEN in prostate cancer and to examine the gene for mutations in Asian men, we analyzed 32 cases of primary prostate cancers from Chinese patients, each of whom was not diagnosed by screening with serum prostate-specific antigen, for PTEN mutations using the methods of tissue microdissection, single-strand conformational polymorphism, and direct DNA sequencing. Seventy % of the tumors were Gleason scores 8-10, whereas the remainder were Gleason score 7. Six metastases of prostate cancer from American patients were also analyzed. Five of 32 (16%) primary prostate cancers from Chinese men and two of six metastases from American men showed mutations in a total of 10 codons of PTEN, which involved exons 1, 2, 5, 8, and 9. Two of the mutations were truncation type, whereas the rest were missense mutations. The mutation frequency in these cases from Asian patients was higher than that in our previous study of cases in radical prostatectomy specimens from American men, in which the 40 primary tumors were lower grade and had been detected by serum prostate-specific antigen test. We conclude that mutation of PTEN occurs more often in primary prostate cancers of Chinese men, whose tumors are high grade and reflective of an unscreened population.

Aged↗
PubMed2001

Genome-wide allelotyping analysis reveals multiple sites of allelic loss in gallbladder carcinoma.

Although gallbladder carcinoma (GBC) is a highly malignant neoplasm, there is very limited information about the molecular changes involved in its pathogenesis. To identify the chromosomal locations of putative tumor suppressor gene loci involved in the pathogenesis of GBC, we conducted a genome-wide allelotyping or loss of heterozygosity (LOH) analysis of GBCS: Microdissected tissue from 24 archival GBCs and their matched control DNAs were analyzed for PCR-based LOH using 169 microsatellite markers spanning all nonacrocentric autosomal arms and the X chromosome. The chromosomal arms with the greatest frequencies of LOH (> or = 60%) were 3p, 6q, 7q, 8p, 9p, 9q, 11q, 12q, 17p, 18q, 19p, 22q, and XQ: The average fractional allele loss index in GBC cases was high (0.43) and frequent breakpoints were detected in gallbladder tumors. Of interest, 21 different regions of frequent LOH (hot spots) defined as > or = 50% for individual GBC samples were detected in this neoplasm, nearly half of them confined to one microsatellite marker. We conclude that in GBC at least 21 chromosomal regions with frequent allele losses are involved, suggesting that several putative tumor suppressor genes are inactivated in its pathogenesis. Overall, these data provide global estimates of the extent of genetic changes leading to GBC and will be useful for the identification of new tumor suppressor genes and for multiple new markers for translational research.

Adenocarcinoma↗
PubMed2001

Aberrations in the fragile histidine triad (FHIT) gene in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) seems to be closely associated with lung carcinogenesis. To identify the genetic characteristics of precancerous IPF lesions in the peripheral lung, we performed PCR-based microsatellite analysis with DNA extracted from microdissected tissues; fluorescent in situ hybridization (FISH) analysis of the fragile histidine triad (FHIT) gene and immunohistochemical analysis of Fhit protein expression in samples of metaplasias and bronchiolar epithelia obtained from patients with IPF. We used four microsatellite markers of the FHIT gene within or flanking the FHIT gene on chromosome 3p for loss of heterozygosity (LOH) analysis. LOH of the FHIT locus was frequently found among the lesions of metaplasias and bronchiolar epithelia in the patients with IPF [62 (52%) of 119 informative lesions]. Fifty-four (73%) of the 74 lesions of metaplasias and bronchiolar epithelia obtained from the IPF patients with lung carcinoma and 8 (17%) of the 46 samples obtained from the IPF patients without lung carcinoma showed LOH at the FHIT gene (P < 0.0001). We confirmed allelic loss in the metaplasias and bronchiolar epithelia of IPF by FISH analysis of the FHIT gene. Additionally, the level of Fhit protein expression in the metaplastic cells of IPF was frequently reduced. Our findings suggest that allelic loss of the FHIT gene may be involved in carcinogenesis in the peripheral lung of patients with IPF.

Acid Anhydride Hydrolases↗
PubMed2002

Aqueous humor in primary open-angle glaucoma contains an increased level of CD44S.

PURPOSE: To determine whether the cell adhesion molecule CD44, the principal receptor of hyaluronan, is altered in the aqueous humor and the anterior segment of patients with primary open-angle glaucoma (POAG). METHODS: The trabecular meshwork (TM), iris, ciliary body, and sclera of POAG and age-matched control eyes preserved in ethanol were microdissected and subjected to 1% Triton X-100 solubilization at 4 degrees C. Western blot analysis was performed using monoclonal antibodies that recognize either CD44H (hematopoietic; extracellular domain) or CD44S (soluble ectodomain). The concentration of soluble CD44S in aqueous and microdissected tissues was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: ELISA of soluble CD44S of aqueous from eyes of patients with POAG indicated that the concentration of soluble CD44S is increased in comparison with that of aqueous from normal eyes (P < 0.0003). Western blot analysis and densitometry of POAG iris and ciliary body revealed a statistically significant increase in the Triton X-100 extraction of CD44H. The predominant increases were in the 180-kDa (P < 0.001) and the 85-kDa (P < 0.001) forms. ELISA of soluble CD44S indicated that the concentration is statistically decreased in iris (P < 0.05), ciliary body (P < 0.001), and TM (P < 0.005) of POAG eyes. CONCLUSIONS: Increased amounts of soluble CD44S in POAG aqueous and Triton X-100-solubilized CD44H characterized POAG in the iris and ciliary body. These soluble CD44 isoforms may influence the activity of the transmembrane CD44H by acting as inhibitors of CD44H and, thereby, adversely influence the cell survival of TM and retinal ganglion cells in POAG.

Aged↗
PubMed2001

[Analysis of loss of heterozygosity on chromosome 6 in human prostate carcinoma and prostatic intraepithelial neoplasia].

OBJECTIVE: To detect the significance of loss of heterozygosity (LOH) on chromosome 6 in prostate carcinoma and high grade prostatic intraepithelial neoplasia (PIN). METHODS: Pure DNA was obtained from prostate neoplasms and normal tissues after tissue microdissection. LOH of chromosome 6 was detected by PCR based microsatellite polymorphism analysis technique using 20 pairs of microsatellite primers in 10 prostate carcinoma cases and 10 high grade PIN cases. RESULTS: Allelic loss at one or more loci was observed on chromosome 6 in 8 of 10 prostate carcinoma cases. 6q21-6q23 and 6q25-6q27 were two of LOH high frequency regions. 5 high grade PIN cases had LOH detected on chromosome 6. CONCLUSIONS: Two high frequency LOH regions were detected on chromosome 6 of prostate carcinoma. Cyclin C, IGF2R genes were two candidate tumor suppressor genes located in these two regions, they may be involved in the initiation and progression of prostate cancer.

Aged↗
PubMed2003

BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma.

BRAF oncogenic mutations have been identified in significant numbers of melanocytic lesions. To correlate BRAF mutation and melanoma progression, we screened BRAF mutations in 65 melanocytic lesions, including nevi, radial growth phase (RGP), vertical growth phase (VGP) melanomas, and melanoma metastases, as well as 25 melanoma cell lines. PCR and direct sequencing were used to analyze DNA samples extracted from laser capture microdissected tissues. A similar high frequency (62-72%) of BRAF oncogenic mutations was identified in melanocytic nevi, VGP, metastatic melanomas, and melanoma cell lines [H. Davies et al., Nature (Lond.), 417: 949-954, 2002; P. M. Pollock et al., Nat. Genet., 33: 19-20, 2002; and M. S. Brose et al., Cancer Res., 62: 6997-7000, 2002]. In striking contrast, we found BRAF lesions in only 10% of the earliest stage or RGP melanomas. These findings imply that BRAF mutations cannot be involved in the initiation of the great majority of melanomas but instead reflect a progression event with important prognostic implications in the transition from the great majority of RGP melanomas to VGP and/or metastatic melanoma.

Disease Progression↗
PubMed2003

Loss of EphB6 expression in metastatic melanoma.

Overexpression of various members of the Eph receptor tyrosine kinases and their ephrin ligands has been frequently reported in cancer. In contrast, a loss of EphB6 gene expression has been correlated with a poor prognosis in human neuroblastoma, suggesting a distinct role for this receptor compared to other family members. More recently, an important role of EphB6 signalling in T-cells has been described, suggesting possibly deleterious immunologic effects of a loss of EphB6 in cancer progression. We investigated the expression of EphB6 in melanocytic tumors. EphB6 mRNA of 22 microdissected tissues (7 benign nevi, 7 melanomas, 8 metastases) and 10 different cell lines (normal melanocytes, non-metastatic/metastatic melanoma cell lines) were measured by quantitative real-time RT-PCR. For visualization of EphB6 protein expression, immunohistochemistry of 32 melanocytic lesions were performed. On the mRNA level, the benign nevi revealed the highest EphB6 expression (mean = 1.43), while melanomas (mean = 0.63) and metastases (mean = 0.08; p=0.001) displayed a progressive and significant reduction of EphB6 expression. Accordingly, established melanoma cell lines with metastatic potential showed low EphB6 expression in comparison to normal melanocytes and to most of the melanoma cell lines. Immunohistochemistry revealed homogeneous staining in common nevi, whereas in malignant melanomas and metastases a heterogeneously positive to completely negative EphB6 staining was observed. Remarkably, Spitz nevi stained similarly to ordinary melanocytic nevi. Taken together, we show that melanoma progression to metastatic disease is associated with a significant reduction of EphB6 gene expression which may have considerable consequences for the prognosis of malignant melanoma patients and possible gene-therapeutic approaches.

Adolescent↗
PubMed2004

Characterization of p53 gene mutations in a Brazilian population with oral squamous cell carcinomas.

Mutations in the p53 tumor suppressor gene are present in approximately 50% of all human cancers. We sought to determine the frequency and type of p53 mutations in squamous cell carcinomas (SCC) of the oral cavity in a Brazilian population. To identify p53 mutations we used PCR-SSCP in tumor tissue microdissected from paraffin- embedded and from fresh-frozen sections followed by direct sequencing of SSCP bands with altered electrophoretic mobility. We identified p53 mutations in 40% of the human SCC analyzed. The mutations were of a broad spectrum, with a preponderance of G --> A and A --> G transitions with an apparent hotspot at the CpG dinucleotide at codon 290. Patient samples were stratified according to tobacco and alcohol consumption as well as by anatomic location of the tumor, and although trends did emerge, no statistically significant associations were obtained between the occurance of TP53 mutations and these lifestyle habits. We conclude that p53 mutations are common among oral cavity cancers in this population, and stress the significance of this study since it is the first analysis of p53 mutation in oral cancer in a southern Brazilian population.

Adult↗