Expression of neu protein, epidermal growth factor receptor, and transforming growth factor alpha in breast cancer. Correlation with clinicopathologic parameters.

The major objectives of this study were twofold: to determine 1) if growth factors or growth factor receptors were expressed similarly or differently in a clinically well-characterized group of breast cancer patients and 2) if these phenotypic characteristics were associated with any of the commonly used prognostic parameters. Formalin-fixed paraffin-embedded tumor tissue from 51 node-positive breast cancer patients were analyzed for the expression of neu, epidermal growth factor-receptor (EGF-R), and transforming growth factor alpha (TGF alpha) using immunoperoxidase staining. Positive membranous staining for neu was observed in 15 (29%) tumors. Over-expression of neu was observed in high-grade, estrogen-receptor-negative tumors (P less than 0.05). Epidermal growth factor receptor was expressed in 22 (43%) of the tumors analyzed and found to a greater degree in estrogen-receptor-negative and high-grade tumors (P less than 0.025). A significant correlation between neu and EGF-R expression was also noted. Tumors expressing membranous staining of neu had a greater than 70% chance of expressing EGF-R (P less than 0.01). Expression of TGF alpha was found in 68% of tumors and TGF alpha was detected in grade 1 and 2 tumor to a greater degree than EGF-R. The authors conclude that assaying tumors for these antigens may give additional phenotypic characteristics that can give further insight into the biology of breast cancer.

The use of fine needle aspirates in the evaluation of progesterone receptor content in breast cancer.

Material obtained by fine needle aspiration (FNA) from 30 surgically removed breast carcinomas was tested for the immunocytochemical localization of progesterone receptor (PR) using a monoclonal antibody (MAb) developed against human breast cancer PR. When compared to values obtained by conventional biochemical analysis of cytosol protein in the same tissue, a semiquantitative relationship suggested that a high intensity (3+) stain in cases in which more than 30% of the cells were positive was compatible with a PR concentration of greater than 200 fmol/mg. An absence of nuclear stain was indicative of a PR concentration of less than 10 fmol/mg, while a stain of an intermediate intensity (2+) or a stain of high intensity (3+) in less than 30% of the cells correlated with a PR level of 51-200 fmol/mg. Only one case in this group showed weak staining with a PR concentration of 85.5 fmol/mg. Cases containing a low concentration of PR (less than 50 fmol/mg) demonstrated a weak nuclear stain (1+) in less than 10% of the cells. Localization of nuclear PR by MAb staining of FNA cytologic specimens affords a relatively simple, inexpensive method of obtaining potentially significant information regarding tumor response to hormonal therapy and the recurrence potential of a tumor in patients with primary breast cancer; at the same time, this technique obviates several important disadvantages of conventional biochemical analysis.

Phenotypic markers for a spectrum of colonic polyps and cancers. The malignancy potential ratio.

The purpose of this study was to determine if a panel of monoclonal antibodies could define phenotypic markers that could be used in risk assessment of a spectrum of colonic polyps and colon cancers. Using the ABC immunoperoxidase technique on formalin-fixed sections of surgical specimens, the following results were obtained: 1) Mab B72.3 demonstrated increased reactivity in villous lesions and cancers compared with hyperplastic polyps and tubular adenomas; 2) Mab anti-CAA demonstrated increased reactivity in polyps compared with colon cancers; and 3) using the two antibodies (Mab B72.3 and Mab anti-CAA), a malignancy ratio was obtained that determined malignancy risk for individual polyps. No hyperplastic polyp gave a positive ratio, but about 30 percent of villous lesions were positive. Over 50 percent of villous lesions greater than 2 cm in size had a positive ratio. The malignancy potential ratio may be a valuable marker in assessing risk of malignancy in an individual case.

Reactivity of the monoclonal antibody B72.3 with fetal antigen: correlation with expression of TAG-72 in human carcinomas.

The monoclonal antibody (MAb) B72.3 recognizes a mucin-like glycoprotein, TAG-72, which has been detected in a spectrum of human carcinomas, but not in the normal tissue counterparts. Using avidin-biotin-peroxidase complex (ABC) immunohistochemical techniques, MAb B72.3 was reacted with formalin-fixed, paraffin-embedded fetal and pediatric tissue sections to determine the extent of expression of the recognized antigen in these tissues. First trimester fetal tissues failed to express detectable antigen. Gastrointestinal epithelia from 13 to 34 weeks gestation demonstrated the most immunoreactivity with B72.3 although bronchial respiratory epithelium of the lung, transitional epithelium from the kidney, Hassall's corpuscles of the thymus, and gonadal tissues from fetuses of both sexes were also reactive. The TAG-72 antigen was not detected in fetal breast, pancreas, liver, spleen, adrenal, or heart. Expression of the TAG-72 antigen in malignancy appears to correlate well with fetal tissue reactivity with B72.3.

Markers of Venezuelan encephalitis virus which distinguish enzootic strains of subtype I-D from those of I-E.

Strains of Venezuelan encephalitis virus isolated from enzootic habitats during interepizootic periods in Middle America and northern South America can be distinguished from each other antigenically by hemagglutination inhibition. This test has provided the basis for the classification of these virus strains into subtypes I-E and I-D, respectively. Virus strains of these two subtypes have been found to differ profoundly with respect to virulence for English short hair guinea pigs. Studies are described which confirm that virus strains of the I-D subtype are guinea pig virulent, and that virulence is not the result of cocycling subpopulations of epizootic subtype I-AB or I-C virions. Two additional markers were found which distinguish subtype I-D and I-E Venezuelan encephalitis virus strains. Firstly, hydroxylapatite chromatography of intact virions at pH 6.5 showed differential elution of I-D and I-E prototype strains. Virions of subtype I-D strains eluted at 0.08 to 0.11 M phosphate, while those of subtype I-E strains eluted at 0.15 to 0.20 M phosphate. Secondly, the isoelectric points of the E1 envelope glycoproteins of the I-D and I-E prototype strains were significantly different; pH 6.85 to 7.00 and pH 7.25 to 7.30, respectively. There was no significant difference in the isoelectric points of the E2 envelope glycoproteins. These distinguishing characteristics most likely reflect a fundamental difference in virion surface structure.