Cervical metastasis from Spitz nevus of the buccal mucosa.

A 23-year-old woman was presented with a prolonged history of a small lump in the buccal mucosa. A local excision was performed. The morphology diagnosed a Spitz nevus and she underwent supplementary excision of scar tissue.

EGFR, HER2, and HER3 expression in laryngeal primary tumors and corresponding metastases.

Background: There are several substances available to target members of the epidermal growth factor receptor (EGFR) family, both for imaging in nuclear medicine and for various forms of therapy. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as a target in systemic tumor therapy. To date, the expression of EGFR family members has only been determined in primary laryngeal carcinomas, and we have not found published data regarding the receptor status in corresponding metastatic lesions.

FBXW7/hCDC4 is a general tumor suppressor in human cancer.

The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the multisubunit ubiquitin ligase SCF (Skp1-Cdc53/Cullin-F-box-protein), has been shown to mediate the ubiquitin-dependent proteolysis of several oncoproteins including cyclin E1, c-Myc, c-Jun, and Notch. The oncogenic potential of Fbxw7 substrates, frequent allelic loss in human cancers, and demonstration that mutation of FBXW7 cooperates with p53 in mouse tumorigenesis have suggested that Fbxw7 could function as a tumor suppressor in human cancer.

EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases.

The expression of EGFR, HER2 and HER3 receptors were analyzed in immunohistochemical preparations from primary esophageal tumours and corresponding lymph node metastases. The goal was to evaluate whether any of these receptors are suitable as targets for radionuclide based imaging and therapy. The receptor expressions were evaluated in parallel samples, primary tumour and metastasis, from each patient (n=51).

A phase II study of epirubicin, cisplatin and capecitabine as neoadjuvant chemotherapy in locally advanced or inflammatory breast cancer.

Aim: To assess the efficacy and safety of epirubicin, capecitabine and cisplatin (EXC) combination therapy in locally advanced breast cancer (LABC) and investigate the predictive value of selected biomarkers.

Methods: Newly diagnosed LABC patients received four 3-weekly cycles of neoadjuvant EXC (epirubicin 60 mg/m(2) day 1; capecitabine 1000 mg/m(2) bid, days 1-14; cisplatin 60 mg/m(2)day 1) and two cycles of post-operative EXC.

Results: Eight (17%) of 48 patients had inflammatory breast cancer.

[177Lu]pertuzumab: experimental therapy of HER-2-expressing xenografts.

Pertuzumab (Omnitarg) is a novel antibody against HER-2, domain II. HER-2 is a tyrosine kinase receptor that is overexpressed in several carcinomas, especially breast cancer. Pertuzumab, labeled with the low-energy beta emitter (177)Lu, might be a candidate for targeted radiotherapy of disseminated HER-2-positive micrometastases.

Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer.

Histologic grading of breast cancer defines morphologic subtypes informative of metastatic potential, although not without considerable interobserver disagreement and clinical heterogeneity particularly among the moderately differentiated grade 2 (G2) tumors. We posited that a gene expression signature capable of discerning tumors of grade 1 (G1) and grade 3 (G3) histology might provide a more objective measure of grade with prognostic benefit for patients with G2 disease. To this end, we studied the expression profiles of 347 primary invasive breast tumors analyzed on Affymetrix microarrays.

SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening.

We studied the effect of postoperative radiotherapy (RT) after breast sector resection for ductal carcinoma in situ (DCIS). The study protocol stipulated radical surgery but microscopically clear margins were not mandatory. We randomised 1,046 operated women to postoperative RT or control between 1987 and 1999.

Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study.

Background: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood.

Methods: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays.

Activated ERK1/2 and phosphorylated oestrogen receptor alpha are associated with improved breast cancer survival in women treated with tamoxifen.

The aim of this study was to investigate the expression of activated (phosphorylated) ERK1/2, oestrogen receptor alpha phosphorylated at S118 (ERalphaS118), and HER2 in primary breast cancer, and to make correlations with the outcome of tamoxifen therapy. We performed immunohistochemical analysis to determine the expression of HER2, ERalphaS118, and activated ERK1/2 in tumours obtained from 279 women with primary breast cancer. HER2 status was also estimated by fluorescence in situ hybridisation.

Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.

Background: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making.

25-Hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-1alpha-hydroxylated vitamin D analogue.

Introduction: The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1alpha-hydroxylated vitamin D analogues to target tissues where 1alpha-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism.

Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts.

Introduction: Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction.

Methods: We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years.

Ductal carcinoma in situ of the breast with different histopathological grades and corresponding new breast tumour events: analysis of loss of heterozygosity.

To compare chromosomal alterations in ductal carcinoma in situ (DCIS) of different histopathological grades and to study aberrations between primary DCIS and corresponding ipsi- or contralateral new in situ or invasive tumours, a study was undertaken of the pattern of loss of heterozygosity (LOH) at chromosomal regions in which LOH has previously been described in invasive breast cancer. LOH was analysed using 19 microsatellite markers located on chromosomes 3p, 6q, 8p, 8q, 9p, 11p, 11q, 16q, 17p, and 17q in 30 women with a primary DCIS. Eleven women with DCIS of grade 1 and 19 with grade 3 according to the EORTC classification system were included.

HER-2, EGFR, COX-2 expression status correlated to microvessel density and survival in resected non-small cell lung cancer.

The incidence of lung cancer is increasing throughout the world and is the most common cause of cancer-related death. Early detection followed by surgery has a reasonable, curative potential, but 30-50% of patients experience relapses. The immunohistochemical expressions of HER-2, EGFR and COX-2 were investigated in 53 resected non-small cell lung carcinomas and correlated to microvessel density and clinical data.

Overexpression of cyclin E protein is associated with specific mutation types in the p53 gene and poor survival in human breast cancer.

Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle. Overexpression of cyclin E has been observed in several malignancies and is associated with high proliferation, aberrant expression of other cell cycle regulators and chromosomal instability in vitro. To explore potential associations between cyclin E deregulation and inactivation of the p53 tumor suppressor gene in human breast cancer, we investigated the immunohistochemical expression of cyclin E in paraffin embedded breast cancers from 270 women with known p53 status by cDNA based sequencing of the p53 gene.