Leena Krogerus

Rapid immunohistochemistry enhances the intraoperative diagnosis of sentinel lymph node metastases in invasive lobular breast carcinoma

The sensitivity of the intraoperative diagnosis of sentinel lymph node (SLN) micrometastases and the metastases of invasive lobular carcinoma (ILC) is low. The goal of the current study was to assess whether the use of intraoperative, rapid immunohistochistochemistry (IHC) enhances the intraoperative detection of micrometastases and metastases of ILC.

Preoperative assessment of proliferative activity and hormonal receptor status in carcinoma of the breast: A comparison of needle aspiration and needle-core biopsies to the surgical specimen

The applicability and reliability of estimates of proliferative activity in breast carcinomas using fine‐needle aspiration (FNA) and needle‐core biopsies (NC) was evaluated in 98 breast carcinoma patients. The Ki‐67, Estrogen receptor (ER), and progesterone receptor (PR) immunolabelling of FNA and NC was compared with that of the surgical specimen. A statistically significant consistency between labelling was found in the Ki‐67‐NC (κ=0.474), ER‐FNA (κ=0.318), ER‐NC (κ=0.518), and PR‐FNA (κ=0.404) groups. The consistency in the Ki‐67‐FNA group was less significant (κ=0.182), and there was no consistency in the PR‐NC group (κ=0.062). There was a positive correlation of Ki‐67 labelling in FNA and NC biopsies (Spearman rank, p=0.4; P=0.0007), and also in ER labeling (Spearman rank p=0.6; P=0.0001. These results indicate that NC and FNA can be used for preoperative assessment of proliferative activity and hormonal status in breast carcinoma. Diagn Cytopathol 1996; 15:205–210.

Cytomegalovirus enhance expression of growth factors during the development of chronic allograft nephropathy in rats

Cytomegalovirus (CMV) accelerates chronic rejection (CRX) in a model of rat kidney allograft. In this model, the expressions of transforming growth factor beta 1 (TGF‐β), platelet‐derived growth factor (PDGF)‐AA, PDGF‐BB and connective tissue growth factor (CTGF) were investigated with and without CMV. Transplantations were performed under immunosuppression. One group of animals was infected with CMV and the other was left uninfected. The grafts were harvested on days 3–60 after transplantation. Growth factor proteins were demonstrated by immunohistochemistry, and mRNAs by in situ hybridization. A significantly more intense and earlier endothelial TGF‐β (2.4u2003±u20030.8 vs. 1.0u2003±u20030.0; Pu2003<u20030.05) and PDGF‐AA (1.8u2003±u20030.4 vs. 1.0u2003±u20030.0; Pu2003<u20030.05) expressions, confirmed by mRNA hybridization, occurred in the CMV group compared with the noninfected group. PDGF‐BB appeared in a few inflammatory cells only. In addition CTGF appeared earlier and has more intense in the CMV group (2.5u2003±u20030.6 vs. 1.2u2003±u20030.5) and the number of CTGF mRNA‐positive fibroblasts (57u2003±u20039 vs. 3u2003±u20034; Pu2003<u20030.05) was significantly higher. Thus, CMV enhanced expression of TGF‐β1, PDGF‐AA and CTGF during the development of CRX.

Biliary dysplasia in patients with primary sclerosing cholangitis: additional value of DNA ploidity

Detection of biliary dysplasia in PSC is essential for proper timing of liver transplantation to prevent the development of cholangiocancer, which is considered a contraindication for liver transplantation in most centres. In patients with PSC, differential diagnosis of benign, premalignant and malignant biliary strictures is difficult.

Time-Related Effects of Cytomegalovirus Infection on the Development of Chronic Renal Allograft Rejection in a Rat Model

Cytomegalovirus (CMV) infection is a risk factor for chronic allograft rejection. The histological findings of chronic renal allograft rejection include inflammation, vascular intimal thickening, glomerulosclerosis, tubular atrophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chronic rejection within 60 days. During the early phase of the process in this model, CMV increased and prolonged the inflammatory response, the expression of adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of various growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which induce smooth muscle cell proliferation in the vascular wall and collagen synthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-infected grafts. In summary, CMV infection accelerated and enhanced the early immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts.

Sequential analysis of adhesion molecules and their ligands in rat renal allografts during the development of chronic rejection.

Abstract Intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) are important in endothelial cell‐leukocyte interactions. In this sequential study, the expression of ICAM‐1 and VCAM‐1 and their ligands LFA‐1 and VLA‐4 as well as major histocompatibility complex class II antigens (MHC class II), and interleukin‐2‐receptor (IL‐2R) were investigated during the development of chronic renal allograft rejection in a rat model. The time‐related expression of adhesion molecules and their ligands in the graft was correlated to the chronic allograft damage index (CADI). In association with an initial short immune activation, there was a significant ICAM‐1 and VCAM‐1 induction in the vascular endothelium and the tubular epithelium. In the interstitium, there was infiltration of lymphocytes expressing ligand molecules VLA‐4 and LFA‐1, as well as activation markers MHC class II and IL‐2R. Thereafter, the expression declined together with the increase of CADI‐values. In end‐stage chronic rejection, there was practically no expression of ICAM‐1 and VCAM‐1. In the interstitium, there were only few ligand‐expressing leukocytes. In conclusion, adhesion molecules and their ligands are involved in the induction phase of the process but no longer in the later stages of chronic rejection.

Long-term results of ablation with antireflux surgery for Barrett's esophagus: a clinical and molecular biologic study.

BackgroundThe initial results from ablation therapy for metaplastic/dysplastic Barrett’s esophagus (BE) are promising, but the results of extended follow-up evaluation are seldom reported.MethodsNeodymium:yttrium–aluminum-garnet laser ablation and successful antireflux surgery for 18 patients with metaplastic BE primarily resulted in the total histologic eradication of BE in 15 patients (83%). After antireflux surgery, the healing of gastroesophageal reflux disease (GERD) was objectively verified in all the patients. At late follow-up evaluation, endoscopy, conventional histology, molecular oxidative stress analyses in comparison with normal control conditions (8-hydroxydeoxyguanosine [8-OHdG], superoxide dismutase [SOD], glutathione [GSH], myeloperoxydase [MP]), and immunohistochemistry (p53, and Cdx2, caudal-related homeobox gene 2, marking intestinal differentiation) of the neosquamous epithelium were performed.ResultsAt the end of the follow-up period (range, 3–15xa0years; mean, 8xa0years), intestinal metaplasia without dysplasia was detected histologically in eight patients (44%). Six patients had macroscopic BE (mean length, 3.5xa0cm; range 1–10xa0cm). The neosquamous epithelium was histologically normal, with no underlying columnar tissue. The fundoplication was endoscopically normal in 14 patients (82%). The 8-OHdG level was higher in the neosquamous epithelium than in the control conditions in the distal esophagus (4.3 vs. 0.52; Pxa0=xa00.0002) and the proximal esophagus (1.8 vs. 0.95; Pxa0=xa00.006). Likewise, SOD activity was higher in the neosquamous epithelium (0.38 vs. 0.12; Pxa0=xa00.0005), whereas MP activity and GSH levels remained normal. Three patients showed slight nuclear p53 expression (typical in normal inflammatory reactions), whereas Cdx2 positivity was confined to one case with recurrent intestinal metaplasia.ConclusionsThe neosquamous mucosa, generated by the ablation of BE and the treatment of GERD with fundoplication, was stable during long-term follow-up evaluation in two-thirds of the patients with initial eradication. It had normal p53 expression and no Cdx2 protein expression. The oxidative stress of the neosquamous esophagus remained high, although the clinical significance of this is unclear.

Sentinel nodes outside level I–II of the axilla and staging in breast cancer

BACKGROUNDnThe aim of the study was to evaluate the incidence of sentinel nodes and sentinel node metastases outside levels I-II of the axilla in breast cancer.nnnPATIENTS AND METHODSnAltogether 170 breast cancer patients with 172 clinically node-negative T1-T2 tumours underwent lymphoscintigraphy and were included in a prospective study.nnnRESULTSnThe lymphoscintigraphy showed sentinel node(s) in the axilla in 150 (87%) breast cancer cases. Thirty (17%) patients had sentinel nodes outside the axilla. Lymphatic drainage solely outside the axilla was encountered in two patients. Lymph node metastases were found in the axilla in 40% and outside the axilla in 17% of the 30 patients with extra-axillary sentinel nodes. Two patients with sentinel node metastases outside the axilla had no axillary metastases.nnnCONCLUSIONnThe biopsy of sentinel nodes outside the axilla is a potential tool for more accurate staging in breast cancer, since it provides additional information as compared to axillary staging alone.