In this prospective study, we determined HER-2 status in primary breast invasive carcinomas and in the paired lymph node metastases (synchronous and metachronous), local recurrence and metachronous distant metastases, to verify the percentage of discordant cases. HercepTest TM and Fluorescence in situ hybridization (FISH) were used to determine HER-2 status on 119 cases of primary infiltrating breast carcinoma and paired metastases (45 cases with synchronous lymph node metastases, 9 cases with metachronous lymph node metastases, 30 cases with local recurrence, and 35 cases with metachronous distant metastases). A therapeutically significant HER-2 status discordance was demonstrated between primary carcinoma and synchronous lymph node metastases (6.7%), local recurrence (13.3%) and metachronous distant metastases (28.6%). In the first comparison, there was a normal HER-2 status in primary tumours and HER-2 amplification in paired metastases, in the second the opposite phenomenon was present, and both types of discordance were evident in the third comparison. Considering the cases of local recurrences and metachronous distant metastases all together, 14 out of 65 cases (21.5%) showed a therapeutically significant discordance of HER-2 status between the primary tumour and the paired metachronous recurrence or metastasis (p < 0.001), the 15.4% of cases showing normal HER-2 status in the primary tumour and HER-2 amplification in the neoplastic relapse. For the treatment of metastatic patients, the evaluation of HER-2 status should be performed in neoplastic tissue from metastatic site, whenever possible. This procedure could be also suggested in the patients that are metastatic at the time of diagnosis. ' 2007 Wiley-Liss, Inc.Key words: breast carcinoma; FISH; HER-2/neu; HercepTest TM ; metastasis The HER-2 proto-oncogene is located on chromosome 17q21 and encodes a transmembrane tyrosine kinase protein, which belongs to the epithelial growth factor receptors (EGFRs) family. Overexpression of the receptor or amplification of the HER-2 gene has been identified in 15-25% of invasive breast carcinomas and is very important both for the prognosis, 1 and for the therapy. 2,3 Trastuzumab is a humanized monoclonal antibody, which is used in the therapy of invasive breast carcinomas overexpressing HER-2 protein and/or showing HER-2 gene amplification. Trastuzumab treatment, in combination with chemotherapy, has given very good results, in terms of disease free survival and overall survival times, in patients with metastatic breast cancer 2 ; moreover, the results of recent trials on the efficacy of the drug in an adjuvant regimen have showed excellent results in terms of drastic reduction of the precocious relapses, when combined with chemotherapy. 4,5 Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) are the techniques recommended for HER-2 determination, according to the algorithm showed in Figure 1. Chromogenic in situ hybridization (CISH) has furnished promising results but is not yet considered an...

Adenomyosis is a disease with a mysterious pathogenesis, defined by an abnormal displacement of the eutopic endometrium deeply and haphazardly inside the myometrium. Angiogenesis has been indicated to play an important role and our aim was to investigate whether vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1alpha (HIF-1alpha) expression and microvessel density (MVD) were different in women with and without adenomyosis. Immunohistochemistry was performed in endometrial tissues in 23 patients who underwent radical hysterectomy for adenomyosis (14) and for ovarian cysts and fibroids (9) at an Academic Hospital. Compared to women without the disease, VEGF expression was increased in endometrium with a normal location in patients with adenomyosis, although not associated to a significant increase of HIF-1alpha and MVD. Moreover, the endometrium with an abnormal location in patients with adenomyosis showed an increased VEGF and HIF-1alpha expression, particularly in the epithelial cells, associated to an increase of MVD, compared with the endometrium in a normal location in the same group of patients. Our present findings suggest that VEGF-mediated angiogenesis might be associated with the development of adenomyosis. In the ectopic foci the abnormal location might contribute to increased HIF-1a expression, stimulation of VEGF production, and increased vessel formation. In endometrium with a normal location, instead, where VEGF increased expression seems not to be correlated with HIF-1alpha increased expression nor with an increased MVD, other mechanisms might be reasonably postulated. Additional studies are required to explore new targeted and more effective treatment modalities.

Several studies suggest that microangiopathy plays a crucial role in the pathogenesis of psoriasis. TNFalpha up-regulates the genetic transcription of VEGF, a pro-angiogenetic cytokine over-expressed in psoriatic skin, which promotes micrangiopathic modifications in psoriatic plaque. Etanercept is a chimeric protein used in the treatment of psoriasis and other immunomediated disorders, which blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. Starting from this data, we retain that etanercept can improve microangiopathy in psoriatic skin by reducing the synthesis of pro-angiogenetic chemokine VEGF. The aims of the study are: to verify the effect of etanercept on cutaneous en plaque capillaries in vivo using intra-vital videocapillaroscopy analysis, to evaluate the relation between the en plaque videocapillaroscopic pattern and the immunohistochemical cutaneous expression of VEGF in psoriasis, and finally to correlate all these in data with clinical disease activity. Eighteen patients (10 male and 8 female, mean age 51, range 21-60) suffering from stable, en plaque type psoriasis, involving at least 10 percent of body surface area (BSA), and not responsive to conventional therapy were included in the study. All the enrolled patients received etanercept 50mg/twice/week, subcutaneously, for 12 weeks, and were carefully followed up for clinical response with PASI score and DLQI index both before (T0) and after 12 weeks (T12) of treatment with etanercept. A well demarcated psoriatic plaque of the extensor surface of upper extremities was chosen to perform an intra-vital videocapillaroscopy analysis (IVCP), and a skin biopsy for immunohistochemical study both at T0 and T12 in all the included patients, in order to evaluate the presence of microangiopathy and its modification after therapy. All the patients experienced a clinical improvement of cutaneous disease with a significant decrease of PASI score (p<0.0001) and DLQI level (p<0.0001), throughout the twelve weeks of treatment. On IVCP analysis, microangiopathy dramatically decreased (p<0.0001), this modification being significantly related with PASI and DLQI decrease at T12. Immunohistochemical expression of VEGF decreased significantly from T0 to T12 (p<0.0001), and was related with a reduction of psoriatic microangiopathy at T12. The results of our videocapillaroscopic and immunohistochemical investigation confirm that the therapeutic potentiality of etanercept is based also on its capability to promote the regression of psoriatic microangiopathy. Moreover, according to these considerations, videocapillaroscopic evaluation of psoriatic plaque, both before and after treatment with etancercept, may be a useful tool to objectively demonstrate its effect on microcirculation.

Prostatic basal cell proliferations range from ordinary basal cell hyperplasia (BCH) to florid basal cell hyperplasia to basal cell carcinoma. The distinction between these forms of BCH, including the variant with prominent nucleoli (formerly called atypical BCH), and basal cell carcinoma depends on morphological and immunohistochemical criteria and, in particular, on the degree of cell proliferation. In florid BCH, the proliferation index is intermediate between ordinary BCH and basal cell carcinoma. Immunohistochemistry is also useful for identifying the cell composition of the basal cell proliferations, including the basal cell nature of the cells, their myoepithelial differentiation, and c-erbB-2 oncoprotein expression. Based on the information derived from the literature and on the appearance and follow up of the case presented here, florid BCH might represent a lesion with an intermediate position between ordinary BCH and basal cell carcinoma. However, criteria useful for the identification of those cases with a true precursor nature are not available. In general, basal cell carcinoma is seen as a low grade carcinoma. The immunohistochemical expression of the c-erbB-2 oncoprotein, similar to that seen in breast cancer, might have therapeutic importance. B asal cell proliferations in the prostate gland exhibit a morphological continuum ranging from basal cell hyperplasia (BCH) in the setting of nodular hyperplasia to malignant basal cell lesions that resemble, to a certain degree, basal cell carcinoma of the skin and adenoid cystic carcinoma of the salivary gland.1 2 A large number of terms have been used for these tumours and related growths.''Basal cell proliferations in the prostate gland exhibit a morphological continuum ranging from basal cell hyperplasia to malignant basal cell lesions''The aim of our paper, which includes a case presentation and discussion, is to review the morphological spectrum and the immunohistochemical findings of basal cell proliferations in the prostate. CASE HISTORYN A 71 year old white man presented in September 1992 with a one year history of increasing urinary obstructive symptoms. Diffuse enlargement of the prostate was documented by transrectal ultrasound and digital rectal examination. Suprapubic (simple) prostatectomy was performed. The preoperative total serum prostate specific antigen (PSA) concentration was 2.5 ng/ml. After the operation PSA decreased to below 1.0 ng/ml. The diagnosis was benign prostatic hyperplasia associated with diffuse BCH.

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This study shows that IL-1β and TNF-α levels in periodontitis patients with T1DM are affected by the duration of diabetes mellitus.

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We reviewed the clinico-pathological features of 73 primary cutaneous B-cell lymphomas (PCBCLs), diagnosed in 10 years in Marche region in central Italy, which included 16 marginal zone lymphomas (MZL), 33 follicle centre lymphomas (FCL) and 24 diffuse large B cell lymphomas (DLBCL). We also investigated the presence of Borrelia burgdorferi in tissues by polymerase chain reaction. Differences in age, sex, location site, response to therapy, disease recurrence and 5-year disease-specific survival were observed among the 3 histological groups. Specific DNA sequences of Borrelia burgdorferi were not detected in any of the 73 cases of PCBCL. We conclude that PCBCLs in Marche region behave according to the literature data and do not seem to be associated with Borrelia burgdorferi. Additional investigations should be performed on other possible etiologies, at least in our geographical area.