We report the full cDNA sequence encoding the human homologue of murine PA2.26 (T1␣-2, podoplanin), a small mucin-type transmembrane glycoprotein originally identified as a cell-surface antigen induced in keratinocytes during mouse skin carcinogenesis. The human PA2.26 gene is expressed as 2 transcripts of 0.9 and 2.7 kb in several normal tissues, such as the placenta, skeletal muscle, heart and lung. Using a specific polyclonal antibody raised against a synthetic peptide of the protein ectodomain, PA2.26 was immunohistochemically detected in about 25% (15/61) of human early oral squamous cell carcinomas. PA2.26 distribution in the tumours was heterogeneous and often restricted to the invasive front. Double immunofluorescence and confocal microscopy analysis showed that PA2.26 colocalized with the membrane cytoskeleton linker ezrin at the surface of tumour cells and that its presence in vivo was associated with downregulation of membrane E-cadherin protein expression. Ectopic expression of human PA2.26 in HeLa carcinoma cells and immortalized HaCaT keratinocytes promoted a redistribution of ezrin to the cell edges, the formation of cell-surface protrusions and reduced Ca 2؉ -dependent cell-cell adhesiveness. These results point to PA2.26 as a novel biomarker for oral squamous cell carcinomas that might be involved in migration/invasion.Key words: mucin; PA2.26; ezrin; E-cadherin; microvilli; OSCC Squamous cell carcinomas (SCCs) of the oral cavity, pharynx and larynx remain a significant public health problem. They represent 2-3% of all malignancies, and their incidence, particularly that of oral SCCs (OSCCs), is increasing in Western countries. 1 In spite of improved therapeutic procedures, the prognosis of OSCC patients remains poor and considerably lower than that of other neoplasias. 2 This fact can be attributed to several factors: failure to respond to available chemotherapy, late presentation of the lesions and lack of suitable markers for early detection and prognosis. 3,4 Hence, the finding of novel tumour markers, particularly those associated with tumour cell invasion and spreading, can help provide a more accurate evaluation of prognosis and a more efficient management of the disease.PA2.26 antigen was identified in our laboratory as a cell-surface protein induced in murine epidermal keratinocytes and dermal fibroblast-like cells during wound healing and chemical carcinogenesis. 5 Sequence analysis of the isolated cDNA and biochemical characterization of the protein revealed that murine PA2.26 is a small mucin-like transmembrane glycoprotein of about 45 kDa, 6 highly homologous to the rat alveolar type I cell marker T1␣ and the podocyte-associated glycoprotein podoplanin. 7,8 Murine PA2.26 nucleotide sequence is almost identical to that of OTS-8 and gp38, markers of the osteoblastic cell lineage and stromal cells in peripheral lymphoid tissues, respectively, 9,10 and completely matches the nucleotide sequence of RANDAM-2, a recently discovered membrane glycoprotein expressed in neuronal cells during m...
In patients with intraoral carcinomas, elective neck treatment should be considered even in cases with a small primary tumor and negative clinical examination because of the high incidence of occult nodal metastases and the tendency to regional recurrences.
Benign symmetrical lipomatosis (BSL) is a rare disorder characterized by the presence of multiple, symmetric, nonencapsulated fat masses in the face, neck, and other areas. Typically, this entity has been related to the presence of three anterior bulges in the neck. The disorder was first described by Brodie in 1846. After that, Madelung in 1888 and Launois and Bensaude in 1898 characterized the disease. There are multiple synonyms for this disorder, such as Madelung's disease, Launois-Bensaude syndrome, and multiple symmetrical lipomatosis. Benign symmetric lipomatosis is usually described in adults from 30 to 60 years old, with an incidence of about 1 in 25,000 and a male-to-female ratio of 15:1 to 30:1. Most cases have no hereditary pattern. More than 90% of the patients have associated alcoholism. The etiology of benign symmetric lipomatosis remains unknown, but an abnormal lipogenesis induced by catecholamines has been observed. The transformation of BSL to a malignant tumor is extremely rare. In the current report, the authors describe two cases of benign symmetric lipomatosis treated in their department and a review of the literature.
These results suggested that IL is associated with locoregional disease recurrence in early-stage oral carcinoma. The presence of IL was a useful discriminator in predicting the outcome of patients with absence of lymph node metastasis.
Our results suggest that G1790A polymorphism in the HIF-1alpha gene might confer susceptibility to OSCC and could be a marker of disfavorable prognosis at early stages.
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