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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular proto-oncogene, ras, is known to play an important role in the regulation of cell growth and proliferation in normal and malignant conditions. The present study was undertaken to immunohistochemically examine the expression of ras protooncogene product p21 in normal human skin and some cutaneous tumours. In normal skin, the expression of p21 was found in sweat glands, sebaceous glands, capillary endothelium, and smooth muscles, while epidermis was devoid of reaction product. Keratoacanthoma and the granular cells of verruca vulgaris were immunoreactive to the antibody for p21. Bowen's disease and squamous cell carcinoma were positive for p21, but basal cell carcinoma and seborrheic keratosis were negative. In mammary and extramammary Paget's diseases, the immunoreactivity was inconsistent. The expression of p21 in malignant melanoma cells was intense, whereas normal melanocytes and nevus cells were devoid of the expression. These results suggest that the expression of p21 does not correlate with nuclear anaplasia and malignant behaviour of cutaneous tumours.
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PMID:Expression of ras proto-oncogene related protein p21 in normal human skin and cutaneous tumours. 132 35

We examined the role of UVR (UV radiation) (UVA, 320-400 nm; UVB, 290-320 nm; and the combination of UVA and UVB) as a promoter in the induction of cutaneous melanoma. One hundred and seventy hairless mice (Skh-hr2), 6-8 weeks old, were treated in 8 groups: group I, DMBA [7,12-dimethylbenz(a)anthracene] plus UVA; group II, DMBA plus UVA plus UVB; group III, DMBA plus UVB; group IV, DMBA; group V, UVA; group VI, UVA plus UVB; group VII, UVB; group VIII, control. DMBA (0.5% solution) was applied once to promote the formation of dermal melanocytic nevus-like lesions while UVR treatments were conducted 3 times/week for 30 weeks. The mice were examined periodically for the development of multiple pigmented lesions, papillomas, squamous cell carcinomas, melanomas, and lymphomas. Treatment with DMBA plus UVA, DMBA plus UVB, and DMBA plus UVA plus UVB stimulated the development of multiple pigmented nevus-like lesions (85-100%) in mice of groups I, II, III, and IV. Upon necroscopy, 27-33% of animals in groups I, II, and III receiving UVR treatments developed clinically and histologically characterized melanomas. Treatment with DMBA alone did not produce melanomas. DMBA-treated animals in groups I, II, and III which received UVR treatments also developed lymphomas (21-50%). Animals treated with DMBA alone or those that received UVB or the combination of UVB plus UVA (without DMBA) developed only papillomas and squamous cell carcinomas (25-47%). Skin tumors were analyzed for the presence of point mutations in the ras gene. Polymerase chain reaction amplification of DNA and selective oligonucleotide hybridization revealed mutations in the 61st codon of the N-ras gene in the precursor nevus-like lesions and melanoma samples studied. This study suggests that UVR (both UVA and UVB) plays a role as a promoter in the stimulation of melanoma and lymphoma development in hairless mice.
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PMID:Role of ultraviolet radiation in the induction of melanocytic tumors in hairless mice following 7,12-dimethylbenz(a)anthracene application and ultraviolet irradiation. 190 31

Ras oncogene expression of malignant melanoma and melanocytic nevus have been immunohistochemically analyzed on formalin-fixed and paraffin-embedded tissues from 26 melanomas and 24 melanocytic nevi with a monoclonal antibody that was generated against Harvey sarcoma virus-derived ras oncogene products (p21ras). We found distinct differences of p21ras expressions by the type of melanoma. Nodular melanoma, epithelioid cell type melanoma, and deeply invading melanoma revealed higher reactivity with anti-p21ras monoclonal antibody than the other types. The reactivity of melanomas appeared to correlate with the degree of malignancy of the melanoma. It was also demonstrated, however, that part of melanocytic nevi reacted with anti-p21ras monoclonal antibody with a relatively strong intensity. Melanocytic nevi with junctional activity and nevus cells located in the epidermis in compound nevi did not show the positive reaction in contrast to dermally located nevus cells that had relatively strong reactivity. The different p21ras expression among the type of tumors may represent the state of tumor cells differentiation with greater expression with more immaturity in the melanocyte lineage. p21ras expression does not appear to represent a marker of malignant transformation.
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PMID:Differential expression of ras oncogene products among the types of human melanomas and melanocytic nevi. 266 10

Ras oncogene expression of malignant melanoma and melanocytic nevus has been immunohistochemically analyzed using monoclonal antibodies which were generated against ras oncogene products (p21ras) derived from Harvey sarcoma virus. Freshly frozen tissues from 11 melanomas and 8 melanocytic nevi were examined by immunofluorescence method, and also, formalin-fixed and paraffin-embedded tissues from 26 melanomas and 24 melanocytic nevi by ABC method. There existed differences of p21ras expressions by the type of melanoma that nodular melanoma, epithelioid cell type melanoma, and deeply invaded melanoma revealed higher reactivity with anti-p21ras monoclonal antibody than the other types. The reactivity of melanomas were, thus, well correlated to the degree of malignancy of melanomas. In melanocytic nevi, dermally located nevus cells had relatively strong reactivity with anti-p21ras monoclonal antibody in contrast to junctional type nevi and the nevus cells located in the epidermis in compound type nevi which did not show the positive reaction. p21ras expressions in both melanomas and melanocytic nevi may represent a marker of the immature state of cells corresponding to early stages of the melanocyte evolution as well as the morphologic and enzymologic characteristics.
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PMID:[Immunohistochemical analysis of ras gene expression in human melanomas and melanocytic nevi]. 267 Jul 26

This study examined noncultured and cultured melanomas and related precursor specimens for (i) mutated ras genes using polymerase chain reaction (PCR) methodology, (ii) correlation of mutated ras genes with differentiation related phenotypic characteristics, (iii) expression of ras-encoded p21 proteins in tissues by immunoperoxidase analysis, (iv) quantitative expression of mutated and wild-type ras encoded p21 proteins by flow cytometry, and (v) correlation between p21 expression, the occurrence of ras mutations, and cell cycle kinetics. The results of these studies are (1) 24% of cultured malignant melanomas have activated ras genes, with N-ras being activated ten times as frequently as Harvey (Ha)-ras. Each example of an activated ras gene showed a mutation at the 61st codon of the protein, with the exception of one melanoma which showed a mutation at codon 13 of the N-ras gene; (2) all the melanomas displaying an activated ras gene had a similar cell surface phenotype and appear to come from a similar phase of differentiation; (3) 5-6% of noncultured primary and metastatic melanomas have mutated ras genes; (4) no ras gene mutations were found in any precursor lesion, specifically normal nevi and dysplastic nevi; (5) immunoperoxidase analysis of paraffin-embedded specimens indicated no quantitative or qualitative alterations in p21 expression that correlate with tumor progression; (6) there were no observable differences in p21 expression between melanoma cells growing exponentially or in plateau phase, or between melanoma cells with or without ras mutations; nor were any cell kinetic differences found between cells with and without mutated ras genes. These studies suggest that the role of ras mutations may be limited to an indirect involvement in the transformation of a subset of melanomas.
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PMID:Analysis of ras oncogenes in malignant melanoma and precursor lesions: correlation of point mutations with differentiation phenotype. 268 63

We have used polymerase chain reaction (PCR), an amplification procedure, and oligonucleotide hybridization to detect ras gene point mutations in DNA from melanoma tumor samples. Genomic DNA was examined from 40 specimens of melanotic lesions, including benign nevi, primary melanomas, lymph node metastases, and systemic metastases. Adjacent normal skin or peripheral blood was analyzed as control material in 28 cases. ras mutations were detected overall in 25% of malignant tumors. In addition, mutations of all three ras genes were detected. We observed ras mutations in 2 of 4 benign atypical nevi (2 X K12), 4 of 22 primary melanomas (3 X K12, 1 X H12, 1 X N61), and 4 of 14 secondary (5 X K12, 1 X N61) tumors. One with a primary melanoma had concurrent K12 and H12, and two patients with secondary tumors had concurrent K12/N61 and K12 Asp/K12 Val mutations, respectively, making a total of 10 of 40 (25%) patients with ras mutations. This is the first demonstration of K-ras mutations in human melanoma. The presence of K-ras mutations in nevi, putative melanoma precursors, suggests that ras activation may be an early event in melanoma development. No correlation between tumor thickness and the presence of a ras mutation was observed.
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PMID:ras mutations in human melanotic lesions: K-ras activation is a frequent and early event in melanoma development. 269 57

Nevus cell components have been observed in up to 40% of melanomas, but little is known of the pathobiology of these components in relation to their malignant potential. We studied 44 nevi of the typical, dysplastic, congenital, and Spitz types with a battery of monoclonal and polyclonal antibodies that react on formalin-fixed, paraffin-embedded tissues (HMB.45, S-100 protein, RAP-5, epithelial membrane antigen [EMA], and neuron-specific enolase [NSE]) by avidin-biotin immunohistochemical methods. EMA and RAP-5 (which detects the ras oncogene-associated P21 protein) were negative in all cases. Melanoma-specific HMB.45 was strongly reactive with the epidermal component and had a weak to negative reaction with the dermal component in the typical nevi. However, the reaction seen with HMB.45 in the junctional component of dysplastic nevi, congenital nevi, and some Spitz nevi was heterogeneous. One Spitz nevi showed HMB.45 staining in a pattern near to that of melanoma. In contrast to HMB.45, S-100 protein labeled nevomelanocytes, regardless of whether they were within the epidermis or dermis, although, in half of the dysplastic nevi, the reaction was heterogeneous, with some atypical cells failing to stain. But, with cytologically atypical junctional component (dysplastic-appearing), congenital nevi also stained heterogeneously for S-100 protein compared with the dermal component. NSE stained the central component of some Spitz nevi more intensely than the lateral component. Junctional nevomelanocytic subsets of some congenital nevi revealed HMB.45 and S-100 reactivity similar to dysplastic nevi.
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PMID:Typical, dysplastic, congenital, and Spitz nevi: a comparative immunohistochemical study. 229 3

Unique and uncommon BamHI allelic restriction fragments of the Ha-ras locus have been reported in the genomes of patients with cancer and of three affected members of a familial melanoma kindred (Krontiris et al., 1986). Analysis of the BamHI and Msp/HpaII restriction fragments of peripheral blood leucocyte DNA from the members of two families with hereditary melanoma (HM)/familial dysplastic naevus syndrome (DNS) revealed that the only Ha-ras allele common to four affected members of one kindred and two from a second kindred, was the 6.7kb allele which is found in 66% of the normal population. This allele was found equally in affected and non-affected family members, and in one affected case was inherited from an unaffected homozygous parent. It was absent in two affected sisters in a third kindred. In the first kindred the karyotype of all three melanoma sufferers was 46XX 9qh+, while six unaffected members had a normal karyotype. BamHI polymorphism of the Ha-ras gene does not identify the affected members in the HM/DNS families studied.
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PMID:Harvey-ras oncogene restriction fragment alleles in familial melanoma kindreds. 287 51

The expression of c-fos, c-myc, Ha-ras, N-ras, EGF-receptor, and cardiac actin genes was examined in 7 normal epidermis, 3 cellular nevi, and 8 skin tumors including 6 malignant and 2 benign tumors of human origin. These genes were transcribed in most normal and tumor tissues, though no tumor-specific expression of proto-oncogenes (c-fos, c-myc, Ha-ras, and N-ras) could be detected. However, there was a characteristic parallelism between the expression of c-fos and c-myc in normal epidermis, while the parallelism was not always definite in skin tumors. The ratio of c-fos/c-myc transcripts in normal epidermis was constant compared with the expression of other genes examined. These data suggest that c-fos and c-myc are expressed in all normal skin tissues, and that maintenance of a constant ratio of c-fos/c-myc is closely related to ordered cell growth of the tissues.
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PMID:Expression of proto-oncogenes in normal and tumor tissues of human skin. 289 96

Four mouse hybridoma cell lines rp12, rp28, rp35 and rp38 producing monoclonal antibodies (MoAbs) reactive with ras oncogene product p21 were established with the use of recombinant proteins as immunogens. Using immunofluorescence, avidin-biotin complex or peroxidase-antiperoxidase methods, the reactivity of rp12, rp28 and rp35 MoAbs was examined in fresh and paraformaldehyde- or formalin fixed tissues of malignant and benign lesions of the skin, lung, stomach, uterus and ovary. These MoAbs strongly reacted with most malignant melanomas, lung cancers, stomach cancers, colon cancers and adenomatous polyps, uterus cancers, and ovary cancers, while they weakly reacted with inflammatory lung tissues, stomach polyps and metaplastic tissues and cervical dysplastic lesions, and did not react with pigmented nevi. The cancers and colon adenomatous polyps showed a high positive cell ratio, with not only cytoplasmic but also membranous localization of the staining, while other tissues had a low positive cell ratio and cytoplasmic staining localization. The MoAbs rp12, rp28 and rp35 could therefore be helpful for differential diagnosis between cancers and benign lesions.
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PMID:[An attempt at using monoclonal antibodies to oncogene products]. 330 May 58


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