Clinico-pathologic features of primary melanoma and sentinel lymph node predictive for non-sentinel lymph node involvement and overall survival in melanoma patients: a single centre observational cohort study.

Objective: Completion Lymph Node Dissection (CLND) is the current standard of practice for patients with a positive Sentinel Lymph Node Biopsy (SLNB). Significant morbidity is associated to CLND, so we tried to evaluate which prognostic variables could predict NSLN invasion in SLN-positive patients and their impact on the overall survival (OS).

Methods: A retrospective chart review of 603 patients that had undergone SLNB for melanoma between 2000 and 2009 at our department was done.

Chemotherapy with or without trastuzumab.

The prognosis of pT1N0M0/stage I breast cancer has generally been considered so favourable that these patients are not routinely offered adjuvant systemic therapy. However, biological heterogeneity within pT1N0M0 dictates diverse outcomes within the subgroup. HER2 gene amplification or protein overexpression is uncommon in pT1N0M0 disease, but, when present, is clearly associated with a higher risk of recurrence.

Underuse of anthracyclines in women with HER-2+ advanced breast cancer.

Anthracyclines are among the most active drugs in breast cancer. Because of excessive cardiotoxicity, their use in combination with trastuzumab has been discouraged in patients with human epidermal growth factor receptor (HER)-2(+) metastatic breast cancer. We sought to describe how this treatment paradigm influenced the use of anthracyclines in this patient setting.

p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in tumour cell scatter and proliferation.

The adaptor protein p140Cap/SNIP is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase (Csk). Here, by gain and loss of function approaches in breast and colon cancer cells, we report that p140Cap immobilizes E-cadherin at the cell membrane and inhibits EGFR and Erk1/2 signalling, blocking scatter and proliferation of cancer cells. p140Cap-dependent regulation of E-cadherin/EGFR cross-talk and cell motility is due to the inhibition of Src kinase.

Teratocarcinoma-derived growth factor-1 is upregulated in aldosterone-producing adenomas and increases aldosterone secretion and inhibits apoptosis in vitro.

Aldosterone-producing adenomas (APA) are a frequent cause of secondary hypertension characterized by autonomous hypersecretion of aldosterone. However, the molecular mechanisms involved in adrenal tumorigenesis and deregulated aldosterone secretion are currently unknown. To identify putative functional genes, a transcriptional screening was performed on 8 APA and 3 normal adrenals (NA) using oligonucleotide microarrays.

Molecular signaling operated by a diet-compatible mixture of oxysterols in up-regulating CD36 receptor in CD68 positive cells.

Oxidation of dietary cholesterol during food storage and processing, and/or that of endogenous cholesterol in the presence of increased steady-state levels of reactive oxygen species, leads to the production of derivatives, termed oxysterols. Among the biochemical effects exerted by an oxysterol mixture, it has recently been observed that marked up-regulation of CD36 scavenger receptor on macrophage cells plays a primary role in foam cell formation. This article reports evidence of a significant co-localization of CD36 receptor with cells of the macrophage lineage, i.

Neuroendocrine differentiation in breast cancer: established facts and unresolved problems.

Neuroendocrine breast carcinoma (NEBC) diagnosis relies on (i) presence of morphologic neuroendocrine features, and (ii) neuroendocrine markers expressed in more than 50% of tumor cells. The World Health Organization classification describes 3 main histologic types: the solid, the small/oat cell, and the large cell variant. In addition, we have recently proposed a further categorization into 5 subgroups: the first 3 categories encompass solid lesions and include (i) solid cohesive carcinomas, (ii) alveolar carcinomas, and (iii) small cell carcinoma; the last subgroups include mucin-producing tumors which are (iv) solid papillary carcinomas and (v) cellular mucinous carcinomas.

Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers.

The purpose of this article is to evaluate the prognostic value of androgen receptor (AR) expression in patients with estrogen receptor (ER)-positive breast cancer, treated with endocrine therapy, with or without the addition of chemotherapy. A consecutive series of 953 patients with ER-positive breast cancer, treated between 1998 and 2003, was selected. Repeated immunohistochemistry confirmed the expression of ER in the tumor of 938 patients.

Trastuzumab with either docetaxel or vinorelbine as first-line treatment for patients with HER2-positive advanced breast cancer: a retrospective comparison.

Background: Combinations of trastuzumab with either docetaxel or vinorelbine are considered valuable treatment options for HER2-positive metastatic breast cancer patients. We performed a retrospective comparison of the clinical outcomes associated with either one of these combinations.

Methods: From a multi-institutional database we retrieved 179 patients treated with either docetaxel or vinorelbine plus trastuzumab as first-line therapy for HER2-positive advanced breast cancer.

Nodal-stage classification in invasive lobular breast carcinoma: influence of different interpretations of the pTNM classification.

PURPOSE Application of current nodal status classification is complicated in lobular breast carcinoma metastases. The aim of this study was to define the optimal interpretation of the pTNM classification in sentinel node (SN) -positive patients to select patients with limited or with a high risk of non-SN involvement. PATIENTS AND METHODS SN metastases of 392 patients with lobular breast carcinoma were reclassified according to interpretations of the European Working Group for Breast Screening Pathology (EWGBSP) and guidelines by Turner et al, and the predictive power for non-SN involvement was assessed.

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results of quality indicators on screen-detected lesions in Italy for 2006 and preliminary results for 2007.

Within this survey, conducted by the Italian Breast Screening Network (Gruppo Italiano per lo Screening Mammografico, GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2006, results showed overall good diagnosis and treatment quality and an improving trend over time. Critical issues were identified in waiting times, compliance with recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray.

Micropapillary ductal carcinoma in situ of the breast: an inter-institutional study.

The clinical significance of micropapillary growth pattern in ductal carcinoma in situ is controversial and the impact of nuclear grading in terms of recurrence of this lesion is yet to be clarified. Our aim was to evaluate, on a series of micropapillary in situ carcinomas, the histological features correlated with recurrence and whether the micropapillary subtype had a different behavior from other non-micropapillary ductal carcinoma in situ. We collected 55 cases of micropapillary in situ carcinomas from four institutions.

Azathioprine, mucosal healing in ulcerative colitis, and the chemoprevention of colitic cancer: a clinical-practice-based forecast.

The development of colorectal cancer in ulcerative colitis is a function of disease duration, with the risk approaching 14% at 25 years. Colitic cancer has become an issue in the last decades, as the availability of effective immune suppressors has reduced resort to curative colectomies. Scrutiny of the available drug options for ulcerative colitis has generated solid evidence of a chemopreventive role of mesalamines.

Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis.

Approximately 8% of breast cancers show increased copy numbers of chromosome 17 centromere (CEP17) by fluorescence in situ hybridization (FISH) (ie average CEP17 >3.0 per nucleus). Currently, this pattern is believed to represent polysomy of chromosome 17.

Mixed micropapillary-ductal carcinomas of the breast: a genomic and immunohistochemical analysis of morphologically distinct components.

Micropapillary carcinomas (MPCs) can present as a rare histological special type of breast cancer; however, this histological type is more frequently found admixed with invasive ductal carcinomas of no special type (IDC-NSTs). We have previously demonstrated that pure MPCs constitute a distinct entity at the morphological and genetic levels. Here, we sought to determine whether mixed MPCs have genomic aberrations similar to those found in pure MPCs, and to investigate whether the distinct morphological components of MPCs harbour different genetic aberrations.

Epidermal growth factor receptor gene in primary tumor and metastatic sites from non-small cell lung cancer.

Introduction: The majority of patients with non-small cell lung cancer (NSCLC) develop distant metastases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are capable of reducing brain and adrenal metastases. However, the EGFR status may be discordant between primary NSCLC and the corresponding metastases.

Columnar cell lesions associated with breast calcifications on vacuum-assisted core biopsies: clinical, radiographic, and histological correlations.

Columnar cell lesions of the breast are increasingly recognized at mammography for their tendency to calcify. We studied 392 vacuum-assisted core biopsies performed solely for calcifications to evaluate the frequency of columnar cell lesions, their relationship with radiological risk, appearance of calcifications, and clinical data. Management and follow-up of columnar cell lesions without and with atypia (flat epithelial atypia) was analyzed.

Anti-HER2 treatment and breast cancer: state of the art, recent patents, and new strategies.

HER2 is a transmembrane tyrosine kinase receptor in the EGFR (epidermal growth factor receptor) family. The role of HER2 has been most thoroughly studied in breast cancer, in which constitutively active HER2 is overexpressed in 18-22% of cases and is correlated with a poor prognosis. Hence, effective inhibition of the constitutive HER2 signaling in cancer cells has been a major goal in the design of therapies.

Added value of combined gene and protein expression of CK20 and CEA in non-macroscopically involved lymph nodes of colorectal cancer.

A methacarn fixation permits an approach that comprises multiple techniques. In this study the procedure is used to examine 100 mesenteric lymph nodes from patients with colon cancer by means of histology, immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR). The evaluated nodes are found to be grossly free of metastases.

Radical resection of a giant, invasive and symptomatic malignant Solitary Fibrous Tumour (SFT) of the pleura.

Solitary Fibrous Tumours (SFTs) of the pleura are rare neoplasms, with unpredictable biological behaviour. Although usually benign, malignant SFTs are described, and they are often associated with large, necrotic and locally invasive tumours. Radical resection represents the treatment of choice in all cases; recurrences are uncommon, and redo-surgery should be considered.

Imatinib inhibits in vitro proliferation of cells derived from a pleural solitary fibrous tumor expressing platelet-derived growth factor receptor-beta.

We examined the in vitro effects of imatinib (Novartis Pharma AG, Basel, Switzerland) as a possible inhibitor of PDGFR pathway on cells derived from a recurrence of a pleural malignant solitary fibrous tumor (SFT). Primary cell culture was characterised by immunofluorescence. SFT-derived cells were treated with imatinib at different time points.

Misclassification of breast cancer as cause of death in a service screening area.

Objective: The aim of this study was to assess the misclassification of cause of death for breast cancer cases, and to evaluate the differential misclassification between cases detected in an organized screening program and cases found in current clinical practice.

Methods: All deaths occurring between 1999 and 2002 within breast cancer cases were linked to hospital discharge records. Death certificates and latest available hospital discharge notes were classified into various categories.

Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era.

Background: Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy.

The genomic profile of HER2-amplified breast cancers: the influence of ER status.

Expression profiling studies have suggested that HER2-amplified breast cancers constitute a heterogeneous group that may be subdivided according to their ER status: HER2-amplified ER-positive breast carcinomas that fall into the luminal B cluster; and HER2-amplified ER-negative cancers which form a distinct molecular subgroup, known as the erbB2 or HER2 subgroup. ER-negative breast cancer differs significantly from ER-positive disease in the pattern, type, and complexity of genetic aberrations. Here we have compared the genomic profiles of ER-positive and ER-negative HER2-amplified cancers using tiling path microarray-based comparative genomic hybridization (aCGH).