The prognostic value of intraepithelial and stromal CD3‐, CD117‐ and CD138‐positive cells in non‐small cell lung carcinoma

Al‐Shibli K, Al‐Saad S, Andersen S, Donnem T, Bremnes RM, Busund L‐T. The prognostic value of intraepithelial and stromal CD3‐, CD117‐ and CD138‐positive cells in non‐small cell lung carcinoma. APMIS 2010; 118: 371–82. The major value of prognostic markers in potentially curable non‐small cell lung carcinoma (NSCLC) should be to guide therapy after surgical treatment. Although tumor‐infiltrating T lymphocytes and plasma cells have been documented in NSCLC, a clear association with clinical outcome, especially for the stromal component, has not been well established. The aim of this study was to elucidate the prognostic significance of these cells/markers in the epithelial and stromal compartments of NSCLC. Tissue microarrays from 335 resected, stage I‐IIIA, NSCLC were constructed by duplicate cores from viable neoplastic epithelial and stromal areas. Immunohistochemistry was used to evaluate the infiltration of CD3⁺, CD117⁺ as well as CD138⁺ cells in epithelial and stromal areas. In univariate analyses, increasing numbers of stromal CD3⁺ (p = 0.001) and epithelial CD3⁺ cells (p = 0.004) correlated significantly with an improved disease‐specific survival. No such relation was noted with CD3⁺ or CD117⁺ cells. In the multivariate analysis, stromal CD3⁺ cells was an independent prognostic factor for disease‐specific survival (HR 1.925, CI 1.21–3.04, p = 0.005). Increased presence of the pan T‐cell marker, CD3, which is an independent factor, correlates with improved clinical outcome in NSCLC. This prognostic impact of T cells is clearer in the tumor stroma. Neither plasma cells nor mast cells were prognostic indicators in our cohort.     

Serum profiles of insulin-like growth factors and their binding proteins in adults with growth hormone receptor deficiency treated with insulin like growth factor I

Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 μgikg S.C. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1–7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I. 0 Laron syndrome, growth hormone receptor deficiency, insulin-like growth factors, insulin-like growth factor binding protein     

Characterization of the potentiation effect of activin on human erythroid colony formation in vitro

Activin, also named FSH-releasing protein, was previously shown to induce hemoglobin accumulation in K562 cells and potentiate the proliferation and differentiation of CFU-E in human bone marrow cultures. Present studies indicate that the potentiation effect of activin is lineage specific. In addition to CFU-E, activin caused an increase in the colony formation of BFU-E from either bone marrow or peripheral blood. It had little effect on the colony formation of CFU- GM and the mixed colonies from CFU-GEMM. In serum-depleted culture, the effect of activin was shown to be dose-dependent with doses effective at picomolar concentrations. The potentiation effect of activin was exerted indirectly through mediation of both monocytes and T lymphocytes. Activin was also found to increase specifically the proportion of DNA-synthesizing erythroid progenitors from both bone marrow and peripheral blood. It had little effect on DNA synthesis in CFU-GM and in mitogen-stimulated lymphocytes. Addition of the monocytes or T lymphocytes to their respective depleted subpopulations of mononuclear cells reconstituted the enhancing effect of activin on the colony formation and DNA synthesis of erythroid progenitors. These results strongly suggest a specific role of activin in potentiating the proliferation and differentiation of erythroid progenitors in vitro.     

A prospective study comparing the haemodynamic with the cross-sectional echocardiographic diagnosis of rheumatic tricuspid stenosis

The value of cross-sectional echocardiography in the diagnosisof tricuspid valve stenosis is not clearly established. We prospectivelystudied by cardiac catheterization 42 consecutive patients,with a mean age of 29 ± 11 years, who exhibited the cross-sectionalechocardiographic features of tricuspid valve stenosis, definedas: diastolic doming of all three tricuspid leaflets and leafletthickening with restrictive motion. To expose occult and amplifyborderline tricuspid diastolic gradients, simultaneous rightatrial and right ventricular pressures were recorded in thebasal state, after incremental infusions of normal saline to200,400,500, 700 or 1000 ml until a mean right atrial pressureof 12 mmHg was achieved, and finally after intravenous administrationof 0.6 mg of atropine. Eighteen patients, Group 1, (43%) exhibitedmean tricuspid diastolic gradients >2mmHg after saline infusion,increasing from a mean of4 ± 2 to 9 ± 3 mmHg,(P <0.001), 14 (33%) having gradients <2mmHg in the basalstate, together with four (10%) increasing from 1.7 ±0.2 to 4.5 ± l.2 mmHg (P <0.01) after provocationwith fluid challenge. In the remaining 24 patients, Group 2,(57%) the mean tricuspid diastolic gradient was <2 mmHg,both at rest and after provocative manoeuvres. We conclude thatthe cross-sectional echocardiographic features of tricuspidvalve stenosis are not a precise indicator of tricuspid valvestenosis. Provocative manoeuvres during haemodynamic studiesare required to expose occult or amplify borderline tricuspiddiastolic gradients in a minority of patients with the cross-sectionalechocardiographic features of tricuspid stenosis.     

Immunohistochemical characterization of a 183 KD myeloid-specific-DNA- binding protein in B5 fixed, paraffin-embedded tissues, and bone marrow aspirates by monoclonal antibody BM-1

A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.     

The presence of leukaemia‐associated phenotypes is an independent predictor of induction failure in acute myeloid leukaemia

Immunophenotyping of acute myeloid leukaemia (AML) has controversial implications with regards to prognosis. The aims of the present study were to determine the frequency of leukaemia‐associated phenotypes (LAP) in AML and to correlate their presence with response to induction chemotherapy. We analysed bone marrow samples at diagnosis from 84 AML patients using triple staining flow cytometry with routine standard panel of monoclonal antibodies. The association of LAP and response to induction chemotherapy was evaluated retrospectively. LAP were observed in 54 (64%) patients: lineage infidelity in 19 (35%), asynchronous antigen expression in 28 (52%), and lack of expected lineage specific antigens in 19 (35%). Significant correlation was found between LAP and responses to induction chemotherapy. Response to induction chemotherapy was more frequent in the absence of LAP (P < 0.05, estimated risk ratio of 1.6, 95%CI, 1.0–2.6) in a multivariate analysis. In conclusion, our data show the presence of LAP in AML is an independent predictor for response to induction chemotherapy and risk of relapse and should be considered for counselling patients and planning therapy.     

Multifocal pyomyositis: report of two cases

Pyomyositis is a primary infection of the striated muscles. We describe the clinical and imaging features of pyomyositis in two patients, one diabetic and the other immunocompetent. Treatment with incision, drainage and antibiotics was successful and resulted in full recovery. Increased awareness, especially in immuno‐competent patients, should lead to earlier diagnosis, correct treatment and a better outcome.