Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. ... more Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma-and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets.
Pseudomyxoma peritonei associated with highly differentiated mutinous, intestinal-type ovarian tu... more Pseudomyxoma peritonei associated with highly differentiated mutinous, intestinal-type ovarian tumor is reported in a 4fGyearold acromegalic patient. Five years after its discovery a second operation revealed a mutinous cystadenoma of the appendix. The coexistence of pseudomyxoma peritonei with ovarian and appendicular tumors is rare, raising questions about the primary origin of the peritoneal tumor. In this case the primary was ovarian while the appendicular tumor occurred later. Since acromegaly is associated with a high risk for the development of colorectal tumors, it could also have elicited a similar response in the intestinal-type ovarian tumor and the appendicular neoplasm found in this patient. The role of appendectomy in the surgical treatment and staging of ovarian tumors is stressed. o 1%~ Academic PRS, IX. Some 40 instances of pseudomyxoma peritonei (PP) associated with coincident mutinous appendicular and ovarian neoplasms have previously been reported 2]. In the present case, sequential ovarian and appendicular tumors occurred together with PP in a patient with acromegaly, a condition known to be associated with a high risk of colonic cancer [3].
A case of cesarean scar endometriosis with massive decidualization is presented. The 25-year-old ... more A case of cesarean scar endometriosis with massive decidualization is presented. The 25-year-old patient had an extensive, ulcerated lesion that mimicked malignancy microscopically due to myxoid change with alveolar patterns reminiscent of some soft tissue sarcomas, signet ring-like cells similar to mucin-producing carcinoma, and pseudoinfiltration of the fascia. The myxoid tissue was positive for acid mucopolysaccarides but negative with PAS. Decidual cells were vimentin positive and keratin negative. No atypia or mitoses were seen. The pseudoinfiltrative aspect was due to abundant extracellular matrix that separated the fascicles of the fascial tissue. There was a metaplastic decidual “proximity effect” in the surrounding, unaffected dermis, which may be responsible for the expansile features of the lesion. This case exemplifies the differential diagnosis of myxoid endometriosis with malignant conditions of the skin.
Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. ... more Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma-and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets.
Pseudomyxoma peritonei associated with highly differentiated mutinous, intestinal-type ovarian tu... more Pseudomyxoma peritonei associated with highly differentiated mutinous, intestinal-type ovarian tumor is reported in a 4fGyearold acromegalic patient. Five years after its discovery a second operation revealed a mutinous cystadenoma of the appendix. The coexistence of pseudomyxoma peritonei with ovarian and appendicular tumors is rare, raising questions about the primary origin of the peritoneal tumor. In this case the primary was ovarian while the appendicular tumor occurred later. Since acromegaly is associated with a high risk for the development of colorectal tumors, it could also have elicited a similar response in the intestinal-type ovarian tumor and the appendicular neoplasm found in this patient. The role of appendectomy in the surgical treatment and staging of ovarian tumors is stressed. o 1%~ Academic PRS, IX. Some 40 instances of pseudomyxoma peritonei (PP) associated with coincident mutinous appendicular and ovarian neoplasms have previously been reported 2]. In the present case, sequential ovarian and appendicular tumors occurred together with PP in a patient with acromegaly, a condition known to be associated with a high risk of colonic cancer [3].
A case of cesarean scar endometriosis with massive decidualization is presented. The 25-year-old ... more A case of cesarean scar endometriosis with massive decidualization is presented. The 25-year-old patient had an extensive, ulcerated lesion that mimicked malignancy microscopically due to myxoid change with alveolar patterns reminiscent of some soft tissue sarcomas, signet ring-like cells similar to mucin-producing carcinoma, and pseudoinfiltration of the fascia. The myxoid tissue was positive for acid mucopolysaccarides but negative with PAS. Decidual cells were vimentin positive and keratin negative. No atypia or mitoses were seen. The pseudoinfiltrative aspect was due to abundant extracellular matrix that separated the fascicles of the fascial tissue. There was a metaplastic decidual “proximity effect” in the surrounding, unaffected dermis, which may be responsible for the expansile features of the lesion. This case exemplifies the differential diagnosis of myxoid endometriosis with malignant conditions of the skin.
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Papers by Juan Linares