Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data obtained in experimental murine tumors and in clinical specimens of human breast cancer have suggested that the nm23 gene may function as a metastasis suppressor gene. In this report we examined the nm23 mRNA level in tumor tissue obtained from distant metastases in 33 patients with malignant melanoma. The gene was differentially expressed in the tumors with a 20-fold range in hybridization intensities. The levels of nm23 mRNA in benign nevi obtained from 12 of the 33 patients were relatively low, with a mean value of 17% of that in the melanomas. In attempts to relate the level of nm23 expression in the tumor metastases to progression of the disease, the time from biopsy of the primary tumor to the appearance of metastases was used as a clinical end point. It was found that patients developing metastases during the first 2 years after diagnosis had significantly lower levels of tumor nm23 expression (56% of the mean value) compared to patients with less aggressive disease (164%) (P < 0.0004). In concordance with previous data the association found here between low levels of nm23 mRNA and the malignant potential of melanomas suggests that the nm23 gene may be implicated in the mechanism of disease progression in some types of human cancer.
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PMID:Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. 135 24

An immunohistochemical investigation regarding the presence of S-100 protein in benign and malignant, primary and metastatic melanocytic tumors is reported. The studied series consisted of 15 benign nevi, 3 blue nevi, 4 juvenile melanomas, 1 balloon cell nevus, 30 primary malignant melanomas of skin, mucous membranes and conjunctiva and 30 metastatic malignant melanomas. The immunohistochemical analysis showed positive staining for S-100 protein within the majority of the tumor cells in all benign tumors examined, except the balloon cell nevus, as well as in all the primary and metastatic malignant melanomas, including low-differentiated epitheloid or spindle-cell types without demonstrable melanin pigment. The results indicate that S-100 protein is a valuable marker for melanocytic tumors, especially in the fairly frequent dilemma of malignant melanoma presenting as a solitary non-pigmented metastasis of uncharacteristic light-microscopic appearance, and without known primary tumor. A characterization and quantification of the S-100 protein immunoreactivity in 5 metastatic malignant melanomas is presented. Using immuno-electrophoresis, the presence of 3 antigenic S-100 determinants was demonstrated within homogenates from the malignant melanomas, including the previously characterized S-100 A (alpha/beta) and S-100 B (beta/beta), and suggesting the presence of a hitherto undescribed variant of S-100 protein, possibly consisting of 2 alpha-subunits. Using rocket immuno-electrophoresis, the amount of S-100 protein was estimated.
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PMID:S-100 protein in melanocytic tumors. An immunohistochemical investigation of benign and malignant melanocytic tumors and metastases of malignant melanoma and a characterization of the antigen in comparison to human brain. 649 75

The records of sixty patients who had a malignant melanoma of the foot or ankle were reviewed retrospectively to determine the clinical features, prognostic factors, and distinguishing characteristics. Fifty-seven patients were white and three were black. There were forty-two women and eighteen men (a female-to-male ratio of 2.3 to 1). The mean age at the time of presentation was fifty-seven years (range, twenty-two to eighty-three years). The most common site of involvement was the plantar aspect of the foot. The mean duration of follow-up was forty-five months (range, three to 144 months). Kaplan-Meier life-table analysis revealed an over-all five-year survival rate of 63 per cent and an over-all ten-year survival rate of 51 per cent. The mean duration of survival for the patients who had a plantar or subungual lesion was significantly shorter than that for the patients who had a lesion at another site on the dorsal aspect of the foot or on the ankle (forty-seven compared with seventy-two months) (p = 0.02). The mean depth of the lesion, according to the criteria of Breslow, was 3.03 millimeters, and the mean level, according to the classification of Clark et al., was IV. According to the classification of the American Joint Commission on Cancer, forty-three patients had stage-I or II (local) disease, thirteen had stage-III disease (nodal or in-transit disease, defined as cutaneous or subcutaneous metastases more than two centimeters from the primary tumor but not beyond the regional lymph nodes), and four had stage-IV disease (distant visceral metastases) at the time of presentation. Lesions at plantar and subungual sites were also associated with a higher prevalence of clinical misdiagnosis compared with lesions on the dorsal aspect of the foot or on the ankle (p = 0.02). The misdiagnoses included a benign nevus (one patient), a paronychia (one patient), a pyogenic granuloma (two patients), a plantar wart (three patients), a ganglion cyst (one patient), a blister (two patients), and a traumatic lesion (five patients).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant melanoma of the foot and ankle. 767 91

CD40 is a receptor at the surface of B lymphocytes with important functions in the immune response. CD40 has also been found on a variety of carcinoma and melanoma cell lines where it has been suggested to serve as a possible receptor for mitogenic signals. We studied the expression and distribution of CD40 in paraffin sections of 71 uniformly treated malignant melanomas (MMs) with a long clinical follow-up using well known monoclonal antibodies. For comparison, 71 benign nevi were also studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity was observed in the dermal part of acquired nevi, and all Spitz' nevi were entirely negative. One-third of large congenital nevi expressed CD40 in small clusters of heavily pigmented, epithelioid cells, corresponding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was expressed in single or clustered neoplastic melanocytes; 9 cases showed CD40 expression only in the radial growth phase, and in 32 cases, the vertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) was studied; in 13 of these 29, CD40L was found in the same tumor areas that expressed CD40. Analysis of 28 metastases from 24 MM patients showed in the majority of cases a similar, scattered or nodular staining pattern as observed in the primary tumor. Patients expressing CD40 in the vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic parameters but showed a significantly shorter tumor-free survival. Patients with CD40+ CD40L+ MM tended to have a shorter tumor-free survival than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous MM. The co-localization of CD40 and CD40L suggests an autocrine growth loop in the vertical growth phase of MM.
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PMID:CD40 is a prognostic marker in primary cutaneous malignant melanoma. 895 30

With the increase in sentinel lymph node biopsies in melanoma patients, pathologists are frequently confronted with small deposits of morphologically bland melanocytes in the node, which occasionally cannot be readily classified as benign nodal nevi or melanoma. As most melanomas harbor characteristic chromosomal aberrations which can be used to distinguish them from benign nevi, we used fluorescence in-situ hybridization (FISH) with markers for 3 regions on chromosome 6 and 1 on chromosome 11 to determine the presence of chromosomal aberrations in sentinel lymph node specimens with small foci of melanocytes that had been diagnosed as metastatic melanoma or nodal nevi by histopathology. Fifty-nine tissue samples from 41 patients (24 lymph node metastases, 17 with nodal nevi, and 18 of the available corresponding primary melanomas) were analyzed by FISH. Twenty of 24 (83%) cases diagnosed as metastatic melanoma showed aberrations by FISH. Of the 4 negative cases, 3 were unequivocal melanoma metastases, whereas 1 on re-review was histopathologically equivocal. Of the 17 nodal nevi, 1 (6%) also showed aberrations by FISH, whereas the remainder was negative. Multiple aberrations were present in the positive case, some of which were also found in the corresponding primary tumor, suggesting that this case represents a deceptively bland melanoma metastasis that had been misclassified by histomorphology. Our data indicate that FISH is a useful adjunct tool to traditional methods in the diagnostic workup of deposits of melanocytes in lymph nodes that are histopathologically ambiguous.
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PMID:Use of fluorescence in situ hybridization (FISH) to distinguish intranodal nevus from metastatic melanoma. 2008 58

NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.
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PMID:Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous melanoma. 2595 64

E-Cadherin and N-cadherin are important components of epithelial-mesenchymal transition (EMT). The majority of studies on EMT in melanoma have been performed with cultured cell lines or pooled melanoma samples. The goal of our study was to evaluate the expression of E-cadherin and N-cadherin in matched tissue samples from primary and metastatic sites of melanoma and to determine the correlation with survival outcome. We analyzed tissues from 42 melanoma primary lesions and their corresponding metastases, as well as 53 benign nevi, for expression levels of E-cadherin and N-cadherin using immunohistochemical methods. There were heterogenous expression patterns of E- and N-cadherin in both primary and metastatic melanomas. Overall, metastatic tumor showed a decrease in E-cadherin expression and an increase in N-cadherin expression compared to the primary tumor, although the difference did not reach statistical significance (p=0.24 and 0.28 respectively). A switch of membranous expression from E-cadherin to N-cadherin from primary to metastatic melanoma was seen in eight patients (19%). Aberrant E-cadherin expression (defined as negative to weak membranous E-cadherin or positive nuclear E-cadherin expression) was more frequently observed in metastatic than in primary melanomas (p=0.03). Multivariate analysis showed that absence of N-cadherin expression in primary melanomas and the presence of aberrant E-cadherin expression in primary melanomas and metastatic melanomas was associated with a significantly worse overall survival. Our data support the importance of E-cadherin and N-cadherin proteins in melanoma progression and patient survival.
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PMID:Epithelial-Mesenchymal Expression Phenotype of Primary Melanoma and Matched Metastases and Relationship with Overall Survival. 2791 67

Melanoma is one of the most immunogenic tumors among human neoplasms, with numerous clinical observations of partial or completely regressed tumors. It is an aggressive tumor, with the greatest reported number of somatic mutations, BRAF mutation being the most common one. BRAF mutation is also present in a higher percentage in benign nevi. Complete regression of primary tumor and involution of nevi are, however, rare phenomenon in melanoma that can appear in relation with UV exposure, surgical trauma, target therapy in melanoma, pregnancy or host immune response to an evolving melanoma tumor. We present the case of a 58-year-old man with a completely regressed metastatic melanoma who developed a second melanoma with concomitant involution of papillomatous nevi under BRAF inhibitors treatment. In reviewed literature we have found 53 cases of completely regressed primary melanomas, neither of them reporting nevi involution. Complete regression of primary tumor can occur as an immune response to tumor progression. Nevi can involute under BRAF inhibitor therapy, but development of new malignant lesions under BRAF inhibitors is linked to BRAF wild-type. Documentation of primary tumor and dynamic changes in nevi highlight the need of a good clinical skin examination and increase the utility of baseline and sequential dermoscopy in melanoma.
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PMID:Complete regression of primary melanoma associated with nevi involution under BRAF inhibitors: A case report and review of the literature. 3094 13