Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty nine benign naevi and 59 melanomas of different Clark level and locations were stained immunohistochemically for the presence of p53 and 3 members of Growth Arrest. DNA Damage inducible family: GADD 34, GADD 45 and GADD 153. All naevi were p53 negative and highly GADD positive. Differences in the expression of all 3 GADD proteins between naevi and melanomas were highly significant (p = 0.0001). The expression of p53 increased and the expression of GADD proteins decreased with the Clark level of melanoma thickness. The survival time of patients correlated negatively with p53 positivity and positively with GADD 45 and 153 expression. Prognostic significance for GADD 34 was not found. Our conclusion is that GADD proteins play an important role in the malignant transformation of naevus to melanoma and GADD 45 and GADD 153 proteins can influence patient survival.
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PMID:Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas. 941 26

A critical area of chromosomal loss at region p16(9p21-22) and p53(17p13) has been implicated in the genesis of malignant melanoma. It is still unclear whether the genetic alterations can be detected in dysplastic nevus, a premalignant lesion of malignant melanoma. We have searched the frequency of p16 and p53 deletion in nine dysplastic nevi and 13 benign intradermal nevi with five microsatellite markers. Hemizygous deletion was detected in seven of nine (78%) dysplastic nevi at one or more loci for p16 and three of seven (43%) for p53, respectively. No loss of heterozygosity (LOH) was detected in any of the benign intradermal nevi. All three dysplastic nevi with LOH for p53 also showed LOH at p16. However, not all dysplastic nevi showing p16 deletion showed p53 gene deletion. Therefore, these data suggest that deletion of p16 may play an important role in the development of dysplastic nevus as an early event and that the changes may represent an early event in the development of malignant melanoma.
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PMID:Allelic deletion at chromosome 9p21(p16) and 17p13(p53) in microdissected sporadic dysplastic nevus. 949 Feb 70

Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine whether allelic loss is of prognostic importance in melanoma, disease-free survival was related to loss of heterozygosity on 6q, 9p and 10q in 83 individuals with sporadic primary cutaneous melanoma. Loss of chromosome arms 6q and 10q were each significantly associated with a poorer clinical outcome (P=0.013 and P=0.001 respectively). In a subgroup of 41 subjects whose primary tumours were allelotyped, the fractional allelic loss (FAL) at 39 autosomal arms also significantly correlated with disease-free survival (P=0.013), with an increase in FAL associated with a poorer outcome; this association remained significant when controlled for tumour thickness (P=0.035). In addition, a greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21WAF1 protein in the primary melanomas than in the benign melanocytic nevi, however, only p53 over-expression was significantly associated with improved survival (P=0.041).
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PMID:Prognostic significance of allelic losses in primary melanoma. 961 30

Epidemiological data strongly implicate sunlight as the principal environmental cause of melanoma; however, critical molecular targets for ultraviolet (UV)-induced melanoma remain to be identified. The p53 tumor suppressor gene is one possible target, being abnormally expressed in 20-40% of primary melanomas. We undertook a population-based molecular epidemiological study with the aim of determining the environmental and phenotypic factors associated with p53-positive and p53-negative melanomas. One hundred fifty cases of melanoma were randomly ascertained from the Queensland Cancer Registry and matched to 150 electoral roll controls. Data on environmental and phenotypic exposures were collected through interviews and physical examination of all participants. Sections of tumor tissue were obtained from 134 (89%) cases and stained with the anti-p53 DO-7 monoclonal antibody (MAb) following microwave antigen retrieval. Of 121 useable sections, 22 tumors (18%) had more than 1% cells with positive staining consistent with abnormalities in p53 expression. Strongest predictors of p53-positive melanoma were inability to tan [odds ratio (OR) 6.8], history of non-melanoma skin cancer (OR 3.2) and site of melanoma: head/neck (OR 2.2) and lower limbs (OR 2.3). In contrast, factors such as nevus density and freckling propensity were strongly associated only with p53-immunonegative melanoma (OR 8.6 for >25 moles; OR 3.0 for heavy facial freckling). Overall, the determinants of p53-positive and p53-negative melanomas were independent and complementary, the former being associated with features of sun-sensitivity and chronic sun exposure, the latter with phenotypic markers of melanocytic proliferation. Our findings are consistent with at least 2 independent pathways in the pathogenesis of melanoma, characterized by environmental induction and p53 overexpression on the one hand and pigment cell instability on the other.
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PMID:p53 expression and risk factors for cutaneous melanoma: a case-control study. 971 52

To investigate the effect of ultraviolet (UV) irradiation on the expression of cell cycle-associated proteins, melanocytic nevi from healthy volunteers were partially covered, irradiated with a defined UV dose, and excised 1 week thereafter. The irradiated and the protected parts were examined separately by conventional microscopy and immunohistochemistry using the antibodies Ki-S11 (Ki-67), Ki-S7 (topoisomerase IIalpha), PC10 (proliferating cell nuclear antigen [PCNA]), DO-7 (p53), 6B6 (p21WAF1/Cip1), and the melanocytic marker HMB-45. DNA nick-end labeling was used as a marker of apoptosis. Irradiation resulted in morphological changes and increased HMB-45 reactivity. Proliferation, as assessed by Ki-67 and topoisomerase IIalpha expression, was also clearly enhanced in the UV-exposed areas. This was confirmed by the appearance of occasional mitotic figures. PCNA expression levels markedly exceeded those of the proliferation markers and did not correlate with the latter in most cases. p21 immunolabeling indices were also consistently augmented after UV exposure; hence it is likely that growth-inhibitory mechanisms partly compensate for the proliferative impulse, and the disproportional rise in PCNA expression probably reflects DNA repair activity. Enhanced p53 immunostaining in four cases suggests that the induction of p21 after irradiation may be p53 mediated, whereas no concomitant apoptotic events were observed. We conclude that UV light can stimulate the proliferative activity of melanocytes in melanocytic nevi, but that simultaneously cell cycle inhibitors are activated to permit DNA repair.
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PMID:Enhanced expression of Ki-67, topoisomerase IIalpha, PCNA, p53 and p21WAF1/Cip1 reflecting proliferation and repair activity in UV-irradiated melanocytic nevi. 986 36

Recently p73, a novel p53 homologous tumour suppressor gene, has been cloned and mapped to chromosome 1p36. Like p53, important functions of p73 in controlling the cell cycle and programmed cell death have been described. Loss of p73 has been demonstrated in neuroblastomas and its involvement in tumorigenesis has been suggested to occur in other neuroectodermal cancers. Since genetic alterations at the tumour suppressor locus 1p36 have been also identified in malignant melanomas, we investigated the expression of p73 in a panel of nine different human melanoma cell lines, 17 melanocytic naevi, 17 primary malignant melanomas and 20 metastases by reverse transcriptase polymerase chain reaction (PCR) and Southern blotting. We observed significant p73 mRNA expression in all the cell lines and tissue specimens except one benign melanocytic naevus and one melanoma metastasis. Sequencing the PCR fragments of nine melanoma cell lines derived from primary tumours and five metastases over the entire p73 DNA binding domain revealed wild-type sequences in all cases. In summary, we conclude that loss of p73 mRNA expression or mutations in the p73 DNA binding domain do not represent common genetic events involved in the pathogenesis of malignant melanomas.
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PMID:Loss of expression or mutations in the p73 tumour suppressor gene are not involved in the pathogenesis of malignant melanomas. 991 12

Aggregates of benign nevus cells occurring in lymph nodes are a well-described incidental finding. Nevus cell aggregates (NCAs) can mimic foci of metastatic carcinoma or other disease processes, so the surgical pathologist should be familiar with this lesion. The purpose of this report is to describe the potential diagnostic difficulties created by benign NCAs within the thymus of a 32-year-old man with dysplastic nevus syndrome and malignant melanoma involving mediastinal lymph nodes and the right lung. Morphologically, the NCAs in this case elicited the differential diagnoses of metastatic melanoma and thymoma. Immunohistochemical studies helped to establish the correct diagnosis by demonstrating reactivity for S-100 protein and negative staining for keratin and HMB-45. Unlike malignant melanomas, NCAs show no p53 protein immunoreactivity, and low proliferative activity was detected by Ki-67 antigen immunostaining. Although melanocytic cells were rarely reported in thymic neoplasms, we are not aware of any previous reports of NCAs occurring in the normal thymus.
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PMID:Benign nevus cell aggregates in the thymus: a case report. 1010 20

A case of malignant melanoma arising from a congenital dermal nevus on the right forehead of a 16-year-old female is presented. In the mole, small pigmented nevoid cells gathered around the skin appendages and between the collagen fibers. From the age of 17, a verrucous nevoid melanoma consisting of lymphoblast-like large nevoid cells, which were positive for HMB-45 and had a high Ki-67 index up to 18.7%, gradually increased in size. The melanoma cells vertically invaded the dermis to a depth of 3 mm and radially spread in the papillary dermis. Twelve years after undergoing a wide local resection and additional chemotherapy, metastatic lesions were found in the lung and the anterior mediastinum, which gradually increased in size and caused death a few months later. Metastatic melanoma cells were positive for HMB-45 and had a high Ki-67 index up to 33.7%. Most metastatic melanoma cells were positive for p53 while the primary ones were negative. Deteriorating mutations probably accumulated during the latent period.
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PMID:Small cell type malignant melanoma which developed in a 16-year-old female with a congenital dermal nevus and metastasized 12 years after excision. 1033 82

Increased expression of p53 has been found in the majority of basal cell carcinomas (BCCs). The pattern and intensity of this staining, as well as staining for proliferation antigens, seems to correlate with behavior of histologic subtypes of BCC. Nevus sebaceus (NS) is considered a hamartoma. Multiple epithelial neoplasms do arise in NS, and, rarely, they show an aggressive biologic behavior. Significant numbers of these neoplasms, however, have areas of basaloid hyperplasia that are often reported as BCC. Although morphologically similar to BCC, the mechanism underlying the development of these areas has not been investigated, so we sought to evaluate the expression of Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, Factor XIIIa, and CD34 in areas showing basaloid hyperplasia, arising in NS. We performed immunohistochemical stains for Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, Factor XIIIa, and CD34 on seven cases of NS with areas of basaloid hyperplasia. All of the eight cases of NS showed diffuse positive membrane staining for Ber-EP4 and negative nuclear staining for p53. Proliferating cell nuclear antigen and Ki-67 staining was only slightly increased in the areas of basaloid hyperplasia, compared with the surrounding epidermis and with areas of the epidermis peripheral to the hamartomatous proliferation, and bcl-2 was only focally positive. Factor XIIIa-positive cells and CD34-positive vascular endothelial cells were increased within the subjacent dermis, a pattern suggestive of follicular differentiation. Our findings suggest that even though areas of basaloid hyperplasia in NS are morphologically similar to BCC, they are induced by different stimulatory and molecular mechanisms. These different mechanisms result in expression of immunohistochemical markers more characteristic of benign follicular tumors than of BCC.
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PMID:Immunohistochemical staining for Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, CD34, and factor XIIIa in nevus sebaceus. 1034 81

A novel gene, termed p73 with significant homology to p53, has been identified at 1p36, a chromosomal region which is frequently deleted in malignant melanoma. To determine whether p73 is involved in melanoma development we analyzed 8 benign melanocytic nevi, 17 primary melanomas, 34 melanoma metastases and 9 melanoma cell lines for p73 alterations. Allelic loss at the p73 locus was observed in 2 of 10 cases (20%) and occurred only in metastatic tumors. Mutation analysis of the DNA-binding domain of p73 revealed no somatic mutations in the tumor specimens and melanoma cell lines analyzed, whereas the p53 gene was mutated in 5 of 9 melanoma cell lines. Expression analysis of p73 using semiquantitative RT-PCR demonstrated that p73 is not expressed or at exceedingly low levels in benign melanocytic nevi, primary melanomas and lymph node metastases, but at various levels in melanoma cell lines. Our data indicate that p73 does not play a role as a tumor suppressor in melanoma development.
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PMID:Lack of p73 mutations and late occurrence of p73 allelic deletions in melanoma tissues and cell lines. 1040 74


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