Furin expression in squamous cell carcinomas of the oral cavity and other sites evaluated by tissue microarray technology.

Furin is a proprotein convertase that activates many cancer development-related substrates such as growth factors, growth factor-receptors, adhesion molecules, and matrix degrading enzymes. Furin expression was studied in sections from tissue microarrays (TMA) and conventional paraffin blocks in a collection of squamous cell carcinomas (SCC) from three different sites. A total of 118 SCCs from the oral cavity, lung and esophagus as well as 34 precursor lesions (intraepithelial neoplasia) from the oral and bronchial mucosae were studied by immunohistochemistry. Furin expression was notably higher in most precursor lesions than in normal epithelia. Tumors from either the TMAs or the conventional blocks showed significant differences when compared to the mostly negative normal epithelia. High levels of furin expression were observed in approximately 50% SCCs of three different sites as well as in precursor lesions of the oral and bronchial mucosae. In addition another 30% showed low furin expression that was localized in all tumor cells including those in a basaloid position. Normal epithelia sometimes showed low level expression but the normal basal cells were always negative. These results show that furin is up-regulated in SCCs from three different organs and validates its use as a tumor marker in both invasive and pre-invasive neoplasia.

Furin expression in squamous cell carcinomas of the oral cavity and other sites evaluated by tissue microarray technology

Furin is a proprotein convertase that activates many cancer development-related substrates such as growth factors, growth factor-receptors, adhesion molecules, and matrix degrading enzymes. Furin expression was studied in sections from tissue microarrays (TMA) and conventional paraffin blocks in a collection of squamous cell carcinomas (SCC) from three different sites. A total of 118 SCCs from the oral cavity, lung and esophagus as well as 34 precursor lesions (intraepithelial neoplasia) from the oral and bronchial mucosae were studied by immunohistochemistry. Furin expression was notably higher in most precursor lesions than in normal epithelia. Tumors from either the TMAs or the conventional blocks showed significant differences when compared to the mostly negative normal epithelia. High levels of furin expression were observed in approximately 50

SCCs of three different sites as well as in precursor lesions of the oral and bronchial mucosae. In addition another 30

showed low furin expression that was localized in all tumor cells including those in a basaloid position. Normal epithelia sometimes showed low level expression but the normal basal cells were always negative. These results show that furin is up-regulated in SCCs from three different organs and validates its use as a tumor marker in both invasive and pre-invasive neoplasia.

Furin expression in squamous cell carcinomas of the oral cavity and other sites evaluated by tissue microarray technology.

Furin is a proprotein convertase that activates many cancer development-related substrates such as growth factors, growth factor-receptors, adhesion molecules, and matrix degrading enzymes. Furin expression was studied in sections from tissue microarrays (TMA) and conventional paraffin blocks in a collection of squamous cell carcinomas (SCC) from three different sites. A total of 118 SCCs from the oral cavity, lung and esophagus as well as 34 precursor lesions (intraepithelial neoplasia) from the oral and bronchial mucosae were studied by immunohistochemistry. Furin expression was notably higher in most precursor lesions than in normal epithelia. Tumors from either the TMAs or the conventional blocks showed significant differences when compared to the mostly negative normal epithelia. High levels of furin expression were observed in approximately 50

SCCs of three different sites as well as in precursor lesions of the oral and bronchial mucosae. In addition another 30

showed low furin expression that was localized in all tumor cells including those in a basaloid position. Normal epithelia sometimes showed low level expression but the normal basal cells were always negative. These results show that furin is up-regulated in SCCs from three different organs and validates its use as a tumor marker in both invasive and pre-invasive neoplasia.

Simultaneous PAGE, immunoblotting, and immunohistochemical analysis of differentiation associated keratins in lesions of the oral mucosa.

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Simultaneous PAGE, immunoblotting, and immunohistochemical analysis of differentiation associated keratins in lesions of the oral mucosa

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Simultaneous PAGE, immunoblotting, and immunohistochemical analysis of differentiation associated keratins in lesions of the oral mucosa.

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

In vivo and in vitro invasiveness of human lung carcinoma cell lines.

Eight cell lines derived from human non-small cell lung carcinomas were used to compare their in vivo invasiveness, in vitro chemoinvasive abilities and type IV collagenase activity. For the evaluation of the in vivo invasive potential, the tumor cells were seeded into deepithelialized rat tracheas and transplanted subcutaneously into nude mice. The invasive behavior of the cells was observed at 4, 8 and 12 weeks and assessed histologically by determination of the levels of penetration of tumor cells into the different layers of the tracheal wall. Except for two cell lines that did not grow at all in vivo, there was a very good correspondence between the levels of in vivo tracheal wall penetration and the in vitro chemoinvasion assay using fibronectin as chemoattractant and Matrigel as barrier. This also correlated very well with the capacity of the cells to secrete type IV collagenase. The in vivo evaluation of invasion using tracheal transplants, although requiring several weeks of experimentation, proved to be very reliable, yielding homogeneous results with little internal variation, and is proposed as a dependable in vivo invasion assay that closely mimics the in vivo human conditions in which most carcinomas develop and eventually invade neighboring tissues.

Distribution of keratins and involucrin in human fetal oral epithelia.

The presence of keratins and involucrin was studied in 9 human fetuses of an age-range between 9 and 24 weeks of gestation. The use of the monoclonal antibodies AE1 and AE3 as well as an anti-involucrin serum enabled developmental changes in the oral epithelia to be assessed. Our study detected some evidence of fetal differentiation patterns different from the adult, i.e. presence of AE3-Positive basal cells and AE1-Positive suprabasal cells in early stages of fetal development. In addition, involucrin was detected as early as 9 weeks of gestation in the superficial cells of the oral cavity epithelium. After the 15th week of gestation the differentiation markers studied gradually adopted adult-type distribution patterns.