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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a new case of sarcomatoid carcinoma, which showed cellular features of basal cell carcinoma and malignant fibrous myxoid histiocytoma. For this new case and rare neoplasm, we propose the designation of sarcomatoid basal cell carcinoma, as both components were intimately intermingled, the spindle cells seemed to arise from epithelial cells, and both tumoral components showed the same immunohistochemistry expression, cytokeratin and P53 protein, suggesting a monoclonal origin. The epithelial component, a basal cell carcinoma, may have been the first component in the carcinogenesis process.
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PMID:Basal cell carcinoma with sarcomatoid features (sarcomatoid carcinoma): report of a case and review of the literature. 1518 34

We described previously a basal cell carcinoma (BCC) and medulloblastoma (MB) phenotype for CD1Ptch1(neo67/+) mice exposed to ionizing radiation. Ptch1 heterozygous mice mimic the predisposition to BCC and MB development of patients affected by nevoid BCC syndrome that inherit a mutant Patched (Ptch1) allele. To examine the impact of genetic background on development of BCCs and other tumors we used two outbred mouse lines characterized by extremely high, carcinogenesis-susceptible (Car-S), and low, carcinogenesis-resistant (Car-R), susceptibility to skin carcinogenesis. Crosses between Ptch1(neo67/+) mice and Car-S (F1S) or Car-R mice (F1R) were exposed to ionizing radiation. F1SPtch1(neo67/+) mice were highly susceptible to radiation-induced BCCs, whereas F1RPtch1(neo67/+) mice were completely resistant, indicating that tumor penetrance can be modulated by genetic background. Development of microscopic and macroscopic BCC lesions was influenced by Car-S and Car-R genotypes, suggesting a genetic-background effect on both initiation and progression of BCC. Susceptibility was additionally increased in N2 backcross mice (Car-S x F1SPtch1(neo67/+)), showing a contribution from recessive-acting Car-S modifiers. The modifying effects of Car-S-derived susceptibility alleles were tissue specific. In fact, despite higher susceptibility to BCC induction, Car-S-derived lines had lower MB incidence compared with CD1Ptch1(neo67/+) mice. BCC-associated somatic events were not influenced by genetic background, as shown by similar rate of wild-type Ptch1 loss in BCCs from F1SPtch1(neo67/+) (93%) and CD1Ptch1(neo67/+) mice (100%). Finally, microsatellite analysis of BCCs showed Ptch1 loss through interstitial deletion. These results are relevant to humans, in which BCC is the commonest malignancy, because this model system may be used to study genes modifying BCC development.
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PMID:Modulation of patched-associated susceptibility to radiation induced tumorigenesis by genetic background. 1517 86

Mutations of mitochondrial DNA (mtDNA) have been proposed to be involved in carcinogenesis. In this study, we applied the polymerase chain reaction techniques to investigate the frequency of occurrence and proportion of mtDNA with length mutations (deletions and tandem duplications) in light-associated skin tumors (actinic keratosis, AK; basal cell carcinoma, BCC; and squamous cell carcinoma, SCC) in aged individuals. We demonstrated the existence of multiple mtDNA deletions and tandem duplications in tissues of AK, BCC, SCC and normal skin. We showed that the frequencies of occurrence of the 4,977 bp and 7,436 bp deletions and tandem duplications (200 bp and 260 bp) of mtDNA in light-associated skin tumors were not significantly different from those of sun-exposed normal skin (p>0.05), but higher than those of non-exposed normal skin (p<0.05). In addition, we found that the proportion of the 4,977 bp-deleted mtDNA in the skin of the same individual was also affected by skin pathologies. The proportion of 4,977 bp-deleted mtDNA in relatively rapid growing tumor cells in SCC was lower than that of normal skin cells. We suggest that the existence of these length mutations of mtDNA in normal, precancerous or cancerous human skin may be attributed to the stochastic effect of photo-damage. However, it is unclear whether the mutations of mtDNA have a direct bearing on carcinogenesis in skin. Future investigation is warranted to elucidate the causal relationship between mtDNA mutations and skin cancers and to address the pathophysiological role of mtDNA mutations in skin cancer development.
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PMID:Mitochondrial DNA mutations in light-associated skin tumors. 1527 51

To elucidate the pathogenesis of vulvar carcinomas, we studied clonality and human papillomavirus (HPV) infection in vulvar epithelial diseases. Monoclonal composition was demonstrated in all 9 invasive tumors (squamous cell carcinoma [SCC], 6; basal cell carcinoma, 1; malignant melanoma, 2), 15 of 20 cases of vulvar intraepithelial neoplasia (VIN), 7 of 9 cases of Paget disease, 2 of 6 cases of lichen sclerosus (LS), and 2 of 3 cases of squamous cell hyperplasia (SCH); high-risk type HPV was revealed in 5 of 6 SCCs and 17 of 20 VINs. These observations might imply that a subset of cases of LS and SCH result from a neoplastic proliferation, similar to VINs but not related to infection with high-risk type HPV. In 1 case of SCC with concurrent VIN 3 in an adjacent lesion, both lesions showed the same pattern of X chromosome inactivation and the presence of HPV-16 in episomal and integrated forms, suggesting that monoclonal expansion triggered by high-risk type HPV integration is an early event for carcinogenesis of HPV-associated SCC.
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PMID:Analysis of clonality and HPV infection in benign, hyperplastic, premalignant, and malignant lesions of the vulvar mucosa. 1532 44

Caucasian renal transplant recipients from Queensland, Australia have the highest non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR) exposure is critical, genetic factors also appear important. We and others have shown that polymorphism in the glutathione S-transferases (GST) is associated with NMSC in UK recipients. However, the effect of high UVR exposure and differences in immunosuppressive regimen on these associations is unknown. In this study, we examined allelism in GSTM1, GSTM3, GSTT1 and GSTP1 in 361 Queensland renal transplant recipients. Data on squamous (SCC) and basal cell carcinoma (BCC), UVR/tobacco exposure and genotype were obtained. Associations with both NMSC risk and numbers were examined using logistic and negative binomial regression, respectively. In the total group, GSTM1 AB [P = 0.049, rate ratio (RR) = 0.23] and GSTM3 AA (P = 0.015, RR = 0.50) were associated with fewer SCC. Recipients were then stratified by prednisolone dose (< or =7 versus >7 mg/day). In the low-dose group, GSTT1 null (P = 0.006, RR = 0.20) and GSTP1 Val/Val (P = 0.021, RR = 0.20) were associated with SCC numbers. In contrast, in the high-dose group, GSTM1 AB (P = 0.009, RR = 0.05), GSTM3 AB (P = 0.042, RR = 2.29) and BB (P = 0.014, RR = 5.31) and GSTP1 Val/Val (P = 0.036, RR = 2.98) were associated with SCC numbers. GSTM1 AB (P = 0.016) and GSTP1 Val/Val (P = 0.046) were also associated with fewer BCC in this group. GSTP1 associations were strongest in recipients with lower UVR/tobacco exposure. The data confirm our UK findings, suggesting that protection against UVR-induced oxidative stress is important in NMSC development in recipients, but that this effect depends on the immunosuppressant regimen.
Carcinogenesis 2005 Jan
PMID:Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients. 1545 20

Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. FOXE3-FOXD2 (1p33), FOXQ1-FOXF2-FOXC1 (6p25.3), and FOXF1-FOXC2-FOXL1 (16q24.1) loci are FOX gene clusters within the human genome. Members of FOX subfamilies A-G, I-L and Q were grouped into class 1 FOX proteins, while members of FOX subfamilies H and M-P were grouped into class 2 FOX proteins. C-terminal basic region within the FOX domain was the common feature of class 1 FOX proteins. FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells. FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in human congenital disorders. FOXA1 gene is amplified and over-expressed in esophageal and lung cancer. FOXM1 gene is up-regulated in pancreatic cancer and basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog (SHH) pathway. FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies. Deregulation of FOX family genes leads to congenital disorders, diabetes mellitus, or carcinogenesis. Expression profiles, genetic alterations and epigenetic changes of FOX family genes as well as binding proteins and target genes of FOX family transcription factors should be comprehensively investigated to develop novel therapeutics and preventives for human diseases.
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PMID:Human FOX gene family (Review). 1549 44

Cutaneous cancers are not uncommon on the face of elderly patients. Melanin should protect, at least in part, against the ultraviolet (UV)-induced neoplastic damage. However, the density in melanin chromatophores is heterogeneous in the epidermis of Caucasian adults. The computerized UV light-enhanced visualization (ULEV) method is a sensitive tool to assess non-invasively this mosaic pattern of intra-epidermal melanin load. In this study, the combination of ULEV pattern analysis and image analysis were performed involving four groups of phototype III Caucasian subjects. The first group was composed of 55 patients aged from 65 to 75 years who suffered from several malignancies of facial skin. The second control group of 55 patients who never had developed skin cancers were matched with the first group for age, sex and phototype. The third group was composed of 80 patients aged from 49 to 59 years who had developed a single basal cell carcinoma. The fourth group comprised 80 age, sex and phototype-matched healthy control subjects. Irrespective of the groups of subjects, a correlation was found between the pattern grading and the objectively determined relative area of subclinical melanoderma. Patients with multiple skin cancers differed from the other groups by the fact that a significantly higher proportion of them exhibited an extensive type of subclinical melanoderma. This feature was also seen in a minority of patients with a single basal cell carcinoma. The extensive subclinical melanoderma pattern is interpreted as a clue for risk, but not as a cause of UV-induced skin carcinogenesis.
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PMID:Mosaic subclinical melanoderma: an Achilles heel for UV-related epidermal carcinogenesis? 1554 15

The development of extensive and severe non-melanoma skin cancer is an extremely common complication of organ transplantation and is assumed to be caused by long-term treatment with anti-rejection drugs (ARD). Despite this florid clinical problem, ARD treatments have been reported to affect experimental murine skin carcinogenesis only weakly. We report here that treatment of cesium-137-irradiated Ptch1+/- mice with immunosuppressive doses of cyclosporine A plus prednisolone for 4-1/2 mo increased basal cell carcinoma burden by 2.5-fold. Thus, these mice provide a good model for study of the effects of long-term administration of ARD on at least one type of non-melanoma skin cancer.
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PMID:Anti-rejection drug treatment increases basal cell carcinoma burden in Ptch1+/- mice. 1565 83

Carcinogenesis is a multi-step series of somatic genetic events. The complexity of this multi-hit process makes it difficult to determine each single event and the definitive outcome of such events. To investigate the genetic alterations in cancer-related genes, sensitive and reliable detection methods are of major importance for generating relevant results. Another critical issue is the quality of starting material which largely affects the outcome of the analysis. Microdissection of cells defined under the microscope ensures a selection of representative material for subsequent genetic analysis. Skin cancer provides an advantageous model for studying the development of cancer. Detectable lesions occur early during tumor progression, facilitating molecular analysis of the cell populations from both preneoplastic and neoplastic lesions. Alterations of the p53 tumor suppressor gene are very common in non-melanoma skin cancer, and dysregulation of p53 pathways appear to be an early event in the tumor development. A high frequency of epidermal p53 clones has been detected in chronically sun-exposed skin. The abundance of clones containing p53 mutated keratinocytes adjacent to basal cell (BCC) and squamous cell carcinoma (SCC) suggests a role in human skin carcinogenesis. Studies using p53 mutations as a clonality marker have suggested a direct link between actinic keratosis, SCC in situ and invasive SCC. Microdissection-based studies have also shown that different parts of individual BCC tumors can share a common p53 mutation yet differ with respect to additional alterations within the p53 gene, consistent with subclonal development within tumors. Here, we present examples of using well-defined cell populations, including single cells, from complex tissue in combination with molecular tools to reveal features involved in skin carcinogenesis.
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PMID:Genetic tumor archeology: microdissection and genetic heterogeneity in squamous and basal cell carcinoma. 1574 39

Non-melanoma skin cancer, i.e. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors and their number is still increasing worldwide. Furthermore, immunosuppression in organ transplant patients strongly contributes to the increase in skin cancer incidence--being 65-250 times more frequent than in the general population. Often these patients suffer from a second and third lesion and the severity of these tumors is linked to their number. SCCs in transplant recipients also appear to be more aggressive. They tend to grow rapidly, show a higher rate of local recurrences and metastasize in 5-8% of the patients (all reviewed in Ref. 2). This largely differs from BCCs which are more frequent in the general population--at a ratio of 4:1 as compared with SCCs--but the number is only increased by a factor of 10 in transplant recipients. This may suggest that 'dormant' SCC precursor cells/lesions are present at a high frequency in the population but they are well controlled by the immune system. BCC, on the other hand, may be less dependent on immune surveillance thereby underlining its different etiology. While for BCC development the genetic hallmark is abrogation of the ptch-sonic hedgehog pathway, little is known about the causal alterations of SCCs. However, the complexity of the genetic alterations (numerical and structural aberration profiles) in SCCs argues for several levels of genomic instability involved in the generation and progression of skin cancer.
Carcinogenesis 2005 Oct
PMID:Non-melanoma skin cancer: what drives tumor development and progression? 1590 7


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