Assessment of proliferating cell nuclear antigen (PCNA) in breast cancer using anti-PCNA PC10 and 19A2: correlation with 5-bromo-2'-deoxyuridine or tritiated thymidine labeling and flow cytometric analysis.

We compared immunohistochemical staining by two monoclonal antibodies, PC10 and 19A2, to standard methods for cell proliferation, 3H-TdR or BrdU labeling index (S-LI) and S-phase fraction by flow cytometry (S-flow). One hundred thirty-two breast carcinomas were studied retrospectively using formalin fixed, paraffin embedded archival tissues on which S-LI and S-flow had been obtained originally. Percentages of tumor cells positive with PC10 and 19A2 correlated well (r = 0.736, p < 0.0001), although the mean marking index for 19A2 was lower and closer to reference measurements than the mean PC10 index. Correlations between PC10 or 19A2 vs. S-LI, S-flow or DNA ploidy (DNAI) were significant in a group of 64 tumors obtained between 1988 and June 1992, and poor in another group of 68 tumors obtained between 1985 and 1988, suggesting deterioration of stainability with prolonged storage. Discrimination of faint staining from negative nuclei was difficult on PCNA stained sections. Carnoy fixation did not improve results over those fixed with formalin. S-flow and S-LI predicted relapse-free survival, but PCNA indices did not. We conclude that PC10 and 19A2 immunostaining of formalin or Carnoy fixed archival breast cancer tissue correlated with reference measures of proliferation only in cases of short storage periods. Although statistically significant, levels of correlation were too low to use PCNA indices for prognosis.

Cell kinetics by bromodeoxyuridine labeling and deoxyribonucleic acid ploidy in prostatic carcinoma needle biopsies.

We studied 63 prostate carcinomas in needle biopsies after labeling in vitro by incubating the entire biopsy specimen with tritiated thymidine or bromodeoxyuridine before fixation. Biopsies from 176 patients were labeled, of which 98 were benign and 78 were carcinomas (15 carcinomas were excluded because of scant tissue). The procedure did not interfere with histological diagnosis. Median labeling index was 0.87% (range 0.1 to 29.3%). A labeling index exceeding 3% was unusual but it may indicate the potential for rapid clinical progression. Deoxyribonucleic acid (DNA) flow cytometry was performed on the last 44 carcinomas using cells shed by the prostatic needle biopsy tissue samples during transportation to the pathology laboratory. A sufficient number of cells were obtained for analysis in 37 cases, of which 6 were DNA aneuploid. Labeling index correlated with Gleason histological grade and score, and data from the 6 DNA aneuploid carcinomas suggest association between DNA aneuploidy and a high labeling index. Estimates of percentage of S-phase cells by flow cytometry did not correlate with variables other than DNA index, and appear to have been affected by a high noise-to-signal ratio (few proliferative cells relative to cellular debris) and inability to discriminate between benign and carcinomatous cells.

Decrease of CD4 cell number and function in HIV-seropositive hemophiliacs in a longitudinal study.

The Regional Hemophilia Center in St. Louis initiated a prospective study beginning in 1982 to measure sequentially T-cell subpopulations and in vitro lymphoproliferative responses in hemophilia A patients. In a cohort of 106 hemophiliacs, the prevalence of HIV-seropositivity increased from 46.7% in 1982 to 74.5% by 1987. There was a persistent gradual decline over time of T helper/inducer (CD4) cells in HIV-seropositive hemophiliacs (P less than .01). This was reflected by an increasing percentage of hemophiliacs with abnormally low CD4 cells (less than 2 standard deviations below the mean of normal individuals) from 6.7% in 1983 to 52.4% in 1987. Function of CD4 cells, as estimated by in vitro lymphoproliferative responses to phytohemagglutinin (PHA) and tetanus toxoid stimulations also demonstrated a decline over the same years. Lymphoproliferative responses to PHA by HIV-seropositive hemophiliacs' mononuclear cells (MNC) declined from a 90.2% normal response in 1983 to a 71.7% normal response in 1987 (P less than .05). Decreased responses to stimulation with the soluble antigen tetanus toxoid were also seen from 1983 compared with 1987 (P less than .05). This was due to an increased percentage of HIV-seropositive hemophiliacs' MNC, which were unresponsive to stimulation to tetanus toxoid (stimulation index less than 3.0) from 20.8% in 1983 to 41.0% in 1987. These findings indicate that HIV-infection was associated over time with a decline of CD4 number and function in a substantial portion of hemophiliacs.

Plantar lentiginous melanoma. A clinicopathologic study.

Twenty cases of plantar melanoma treated at Ellis Fischel State Cancer Center (EFSCC) since 1940 are analyzed to determine the clinical and histologic features of prognostic significance. The EFSCC experience confirms and extends the observations made in other recent studies of plantar melanoma. This clinical pathologic study suggests that one of the histologic patterns, the lentiginous growth pattern, shares some biologic features with lentigo maligna, namely the relatively indolent growth phase. Plantar melanomas may remain latent for a number of years making these patients good candidates for therapeutic cures if detected early.

Human T4+ T-lymphocyte clones specific for the B fragment of tetanus toxin.

Two T4+ cloned T-lymphocyte lines specific for a papain digest product of tetanus toxin are functionally characterized. The two clones were obtained from peripheral blood mononuclear cells activated in vitro by tetanus toxoid, expanded with IL-2, and cloned in soft agar. Both clones could be induced to undergo blastogenesis with tetanus toxoid, tetanus toxin, and the B fragment but not the C fragment of tetanus toxin. In addition, both clones caused cytolysis of plastic adherent cell targets cocultured for 18 hr with either tetanus or the B fragment. Antigen specific proliferation and cytolytic activity were MHC-class I restricted.

Endobronchial hamartoma.

We have reported a case of endobronchial hamartoma in a mainstem bronchus. Diagnosis of these rare lesions may be difficult when chronic pulmonary destruction has occurred; biopsy of the tumor may show cellular atypia due to inflammation. Although bronchoscopic removal or removal by bronchotomy or sleeve resection with preservation of the lung may be possible, when irreversible lung damage has occurred because of chronic obstruction and suppuration, pulmonary resection may be indicated.

A simplified micro ELISA procedure for the measurement of platelet-associated IgG (PAIgG).

A simplified micro ELISA procedure to measure platelet-associated IgG is described. The platelet-bound IgG first is extracted into the fluid phase by solubilizing washed platelets in 0.1% triton X-100. The solubilized IgG in the extract and IgG standards are incubated in microtiter wells previously coated with antihuman IgG. The IgG in the standards and extract bind to the solid phase antihuman IgG. The bound IgG then is measured by the addition of peroxidase labeled antihuman IgG and appropriate substrate. With this method platelets from normal controls were found to have 1.7 +/- 0.6 fg IgG/platelet (mean +/- SD). Platelets from patients with ATP had values that were two to seven times the control values. The relative advantage of this technic is discussed.

Multifocal recurrent adult rhabdomyoma.

The clinical and morphologic features of a recurrent, multifocal, adult, extracardiac rhabdomyoma are reported. This benign skeletal muscle neoplasm is composed of large round to polyhedral cells containing cross striations. The ultrastructural features consist of hypertrophic Z bands, intranuclear inclusions, and numerous mitochondria with linear, intracristal inclusions. The low thymidine labeling index and long potential doubling time correspond wi th the length of time for clinical recurrence.