No abstract

VCAM (CD-106) and VCAM (CD -54) Adhesion (N.D. Melendez et al.) 13

No abstract

Formalin-fixed, paraffin-embedded tissue sections from 45 patients with mammary and extramammary Paget's disease were stained immunohistochemically with the use of a polyclonal antiserum directed against a 14-amino acid segment of the c-erbB-2 oncoprotein. Positive membrane staining, which correlates with gene amplification, was found in 15 of 19 cases (79%) of mammary Paget's disease, 4 of 13 cases (31%) of vulvar Paget's disease, none of 8 cases of scrotal Paget's disease, and none of 5 cases of perianal Paget's disease. Of the 19 patients with mammary Paget's disease, specimens of underlying breast tissue were available from 14; all contained a concurrent ductal adenocarcinoma. Concordance of c-erbB-2 antigen staining between the underlying breast carcinoma and the pagetoid component was observed in 12 cases. Of the 13 patients with vulvar Paget's disease, 2 had superficial stromal invasion, and 3 had underlying, deeply invasive adenocarcinomas. One superficially invasive case was positive for c-erbB-2 expression. One additional case of vulvar Paget's disease had an associated primary pagetoid endocervical adenocarcinoma that spread into the endometrium; both the endocervical and vulvar components stained positively for the c-erbB-2 antigen. The results of this study indicate that the c-erbB-2 oncoprotein may play a role in the pathogenesis of extramammary Paget's disease. These results also suggest that the c-erbB-2 oncoprotein may function in vivo to promote intraepithelial spread of adenocarcinoma cells.

SUMMARY The Lewis lung carcinoma growing subcutaneously in the hind leg of male C57BL mice is very hypoxic, having 92% of the p 0 2 measurements ~5 mmHg as determined with a polarographic oxygen electrode. Administration of a perflubron emulsion (8 mVkg) along with carbogen breathing increased the tumor oxygen level so that 82% of the PO, readings were 6 5 mmHg. Treating tumor-bearing animals with TNP-470 (30 mgkg, s.c.) on alternate days and minocycline (10 mgkg, i.p.) daily beginning on day 4 after tumor cell implantation resulted in decreased hypoxia in the tumors on day 9 when p 0 2 measurements were made. The percent of p 0 2 readings s 5 mmHg in the tumors of the TNP-470/ minocycline-treated animals was 75%, which upon administration of the perflubron emulsion along with carbogen breathing was reduced to 45 YO. Therapeutically daily fractionated radiation (2, 3, or 4 Gy x 5 ) was used as an oxygen-dependent cytotoxic modality. The radiation response of the tumors in TNP-470/minocycline-treated animals was greater than that in the untreated tumors. The addition of carbogen breathing for 1 hr prior to and during radiation delivery further increased the radiation response so that overall there was a 2.2-fold increase in the tumor growth delay produced by the fractionated radiation in the animals treated with TNP-470/minocycline compared with untreated animals. Administration of the perflubron emulsion along with carbogen breathing prior to and during radiation delivery resulted in a 3.4-fold increase in tumor growth delay by the fractionated radiation regimens in the TNP-470/minocycline-treated animals compared with the tumor growth delay obtained with radiation alone. There was a linear relationship between decrease in the percent of pOz readings s5 mmHg and tumor growth delay at each radiation dose indicating that the diminution in tumor hypoxia produced by these treatments may be directly responsible for the increase in the effectiveness of the radiation therapy.

Adenocarcinomas of the uterine cervix show a wide range of morphological features, and can be confused with endometrial adenocarcinoma in biopsy or curetting specimens. The objective of this study was to use tissue microarray technology to evaluate the immunoprofile of a large set of uterine adenocarcinomas with an extended panel of antibodies, comparing the profile of primary cervical and endometrial adenocarcinomas. A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 141 hysterectomy specimens. Duplicate 0.6-mm cores were obtained from 57 cervical adenocarcinomas (16 in situ and 41 invasive) and 84 endometrial adenocarcinomas. Tissue array sections were immunostained with 21 commercially available antibodies [B72.3, CD 99, carcinoembryonic antigen (CEA), c-kit, pancytokeratin, CK 5/ 6, CK 7, CK8/18, CK19, CK 20, CK 22, EMA, estrogen receptor (ER), KP-1, melan-A, p53, PLAP, S-100, synaptophysin, TTF-1, and vimentin] utilizing the avidin-biotin (ABC) technique. Hierarchical clustering analysis of the tumors was done based on the immunostaining results. Only ER (P<0.001), CEA (P=0.04), vimentin (P<0.001), and CK 8/18 (P=0.002) showed a significantly different frequency of positivity in endometrial relative to cervical adenocarcinomas. ER, vimentin, and CK 8/18 were more likely to be expressed in endometrial adenocarcinomas, while cervical adenocarcinomas more fre-quently expressed CEA. We were able to identify immunoprofiles that were highly specific for endocervical adenocarcinoma (ER , vimentin , CK 8/18 , CEA + ) or endometrial adenocarcinoma (ER + , vimentin + , CK 8/18 + , CEA ), but most tumors showed an intermediate, nonspecific immunophenotype. Hierarchical clustering analysis was useful in the interpretation of these intermediate immunophenotypes. Papillary serous adenocarcinoma of the endometrium was less likely to express vimentin (P=0.002) than endometrioid carcinoma of the endometrium.

No abstract

No abstract