Qualitative assessment of the progesterone receptor and HER2 improves the Nottingham Prognostic Index up to 5 years after breast cancer diagnosis.

Purpose: To investigate whether the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) can improve the Nottingham Prognostic Index (NPI) in the classification of patients with primary operable breast cancer for disease-free survival (DFS).

Patients And Methods: The analysis is based on 1,927 patients with breast cancer treated between 2000 and 2005 at the University Hospitals, Leuven. We compared performances of NPI with and without ER, PR and/or HER2.

Quantity and quality of retrograde menstruation: a case control study.

Background: The purpose of this study was to test the hypothesis that menstruation is associated with a higher concentration of endometrial cells in peritoneal fluid(PF) and with increased white and red blood cell concentration in PF when compared to nonmenstrual phases of the cycle.

Methods: PF was obtained at laparoscopy from 107 women with endometriosis (n = 59) and controls with a normal pelvis (n = 48) during the luteal (n = 46), follicular (n = 38) or menstrual (n = 23) phase of the cycle. Endometriosis was classified according to the classification of the American Society for Reproductive Medicine (rAFS into minimal (n = 25), mild(n = 20), moderate(n = 6) and severe(n = 8) disease.

Triple negative breast cancer: a study from the point of view of basal CK5/6 and HER-1.

Aim: Basal-like breast tumours, as defined by microarrays, carry a poor prognosis and therapeutic options are limited to date. Often, these tumours are defined as oestrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER-2) negative (triple negative) by immunohistochemistry (IHC), but a more complete definition should include expression of basal cytokeratins (CK5/6, CK14 or CK17) and/or human epidermal growth factor receptor 1 (HER-1). The aim of this study was to investigate to what extent CK5/6 and HER-1 characterise the group of triple negative breast cancers.

Belgian consensus guidelines for follow-up of women with cervical cytological abnormalities.

In medical care cervical cancer screening is important because it enables the detection of precancer and cancer at an early stage. By adequate treatment after a screening-detected lesion it helps to reduce the mortality related to cervical cancer. Worldwide, many millions of women have smears taken at a more or less regular base and of these, approximately 7% are abnormal, and follow-up is thus required.

Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing.

Purpose: Polysomy 17 is frequently found in breast cancer and may complicate the interpretation of HER-2 testing results. We investigated the impact of polysomy 17 on HER-2 testing and studied its clinicopathologic significance in relation to HER2 gene amplification.

Patients And Methods: In 226 patients with primary invasive breast carcinoma, HER2 gene and chromosome 17 copy numbers were determined by dual-color fluorescent in situ hybridization (FISH).

Adenomyoepitheliomatous lesions of the mammary glands in transgenic mice with targeted PLAG1 overexpression.

PLAG1 proto-oncogene overexpression has been causally linked to multiple tumors, highlighting its broad tumorigenic relevance. Here, the oncogenic potential of PLAG1 in mammary gland tumorigenesis was investigated in PLAG1 transgenic mice. To target mammary glands, mice of 2 independent PLAG1 transgenic strains, PTMS1 and PTMS2, in which PLAG1 expression can be modulated by Cre-mediation, were crossed with MMTV-Cre transgenic mice, resulting in P1-MCre and P2-MCre offspring, respectively.

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors.

Introduction: Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the short-term disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype.

Patients And Methods: Short-term follow-up (FU) of a prospective cohort of 1,958 breast-cancer patients primary operated at our institution between 2000 and 2005.

Expression of the BRCA1-interacting protein Brip1/BACH1/FANCJ is driven by E2F and correlates with human breast cancer malignancy.

Mutations in the BRCA1-interacting DEAH helicase Brip1 confer an increased risk of breast cancer. In the present study we aimed to unravel the transcriptional control of Brip1 and to determine its expression levels in a set of 101 primary invasive breast carcinomas. Transcription of Brip1 was found to be cell growth-related and controlled by the E2F/retinoblastoma (Rb) pathway through a conserved E2F-responsive site.

A thyroid thriller: acute transient and symmetric goiter after fine-needle aspiration of a solitary thyroid nodule.

Objective: To report a case of a patient who developed an acute and transient, tender, and bilateral swelling of the thyroid that occurred during fine-needle aspiration (FNA) of a solitary nodule in the left thyroid lobe; to add accurate ultrasound measurements to support our clinical observation; and to analyze a possible underlying mechanism of this rare condition. RESULTS AND CLINICAL FOLLOW-UP: The calculated thyroid volume increased from 23 to 57 mL before and at 4 minutes, respectively, after the needle aspiration, but the thyroid volume returned to prediagnostic level after 4 hours. Cytology, serum calcitonin, and histology were concordant, and the nodule was diagnosed as a medullary thyroid carcinoma.

Axillary lymph node status of operable breast cancers by combined steroid receptor and HER-2 status: triple positive tumours are more likely lymph node positive.

Aims: To examine the frequency of axillary lymph node (ALN) invasion of operable breast cancers by their combined oestrogen receptor (ER), progesterone receptor (PR) and HER-2 status.

Methods: 2227 recently operated cases in one centre were retrieved from the Multidisciplinary Breast Centre database and stratified according to their combined immunohistochemical (IHC) expression of ER/PR/HER-2 status. An equivocal HER-2 status was further analysed by Fluorescence in situ Hybridisation (FISH).

The complexity of genotypic alterations underlying HER2-positive breast cancer: an explanation for its clinical heterogeneity.

Purpose Of Review: We discuss recent findings on the genotypic alterations associated with HER2-positive breast cancer in an attempt to clarify the clinical heterogeneity observed among these tumors.

Recent Findings: Molecular genetic analysis supports the distinctive nature of HER2-positive breast cancer, which is primarily driven by HER2 gene amplification. Depending on the amplicon size, a variety of genes can be coamplified and overexpressed together with HER2, some of which may contribute to tumorigenesis; the amplicon size may even predict response to trastuzumab therapy.

The future of cytopathology in Europe. Will the wider use of HPV testing have an impact on the provision of cervical screening?

The emphasis of the EFCS Congress held in Venice in October 2006 was on the future of Cytopathology in relation to events in Europe. Much of the discussion centred on the role of human papilloma virus testing and its impact on the provision of cervical screening. The following is a transcript of the discussion that took place at the Advisory Board Meeting for the journal Cytopathology, with some additional written comments received prior to the meeting.

Validation of clinical prediction rules for a low probability of nonsentinel and extensive lymph node involvement in breast cancer patients.

Background: Two recently developed clinical prediction rules aim to anticipate the lack of nonsentinel lymph node metastases and the involvement of less than 4 lymph nodes in breast cancer patients with positive sentinel lymph nodes (SLNs).

Methods: The University of Louisville Breast SLN Study clinical prediction rules were validated on an independent set of SLN-positive patients with tumors < or = 15 mm.

Results: The data on 475 and 473 patients, respectively, were used for the validation.

Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer.

Background: The negative association between the oestrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER-2) in breast cancer travels in both directions. ER+ tumours are less likely HER-2+ and HER-2+ tumours are less likely ER+.

Methods: We studied the age-related immunohistochemical (IHC) expression of ER, progesterone receptor (PR) and HER-2 in 2,227 tumours using age as a continuous variable.

The E2F-regulated gene Chk1 is highly expressed in triple-negative estrogen receptor /progesterone receptor /HER-2 breast carcinomas.

We previously showed that checkpoint kinase 1 (Chk1) and Claspin, two DNA-damage checkpoint proteins, were down-regulated by 1,25-dihydroxyvitamin D(3), a known inhibitor of cell proliferation. In the present study, we aimed to investigate the transcriptional regulation of Chk1 and Claspin and to study their expression levels in human breast cancer tissue. Transient transfection experiments in MCF-7 breast cancer cells showed that promoter activities of Chk1 and Claspin were regulated by the E2F family of transcription factors.

Sentinel lymph node biopsy and non-sentinel node involvement in special type breast carcinomas with a good prognosis.

This study aimed at identifying factors related to sentinel lymph node (SLN) involvement in patients with tubular, cribriform, mucinous or papillary breast carcinoma and those related to non-SLN metastases if an SLN was positive. Multivariate analyses involved logistic and stepwise regressions. The SLNs harboured metastases in 85 of 572 cases, 78 of whom underwent axillary dissection; 19 presented non-SLN positive disease.

Matrix metalloproteinase expression patterns in luminal A type breast carcinomas.

Objective: Aberrant expression of individual matrix metalloproteinases has been associated with poor prognosis in various human carcinomas. The current study aimed at defining an RNA expression profile of various MMPs in breast cancer and correlating their expression with clinicopathological parameters.

Methods: The RNA expression patterns of 6 MMPs (MMP2, MMP8, MMP9, MMP10, MMP11, MMP13) were determined in 25 breast carcinomas using quantitative RT-PCR and correlated with clinicopathological parameters, including menopausal status, tumor size and grade, and lymph node involvement.

Prophylactic mastectomy in familial breast carcinoma. What do the pathologic findings learn us?

Objective: To evaluate the indications, techniques and pathologic findings of prophylactic mastectomy (pME).

Methods: Retrospective study of patients with a strong family history of breast cancer (and ovarian cancer) or with proven BRCA mutation.

Results: Between January 1995 and December 2005, sixty seven patients underwent pME: 15% had a BRCA1 mutation, 31% had a BRCA2 mutation and 33% had a strong family history but without proven BRCA mutation and in 21% mutation analysis was not performed.

Sentinel lymph node biopsy in staging small (up to 15 mm) breast carcinomas. Results from a European multi-institutional study.

Sentinel lymph node (SLN) biopsy has become the preferred method for the nodal staging of early breast cancer, but controversy exists regarding its universal use and consequences in small tumors. 2929 cases of breast carcinomas not larger than 15 mm and staged with SLN biopsy with or without axillary dissection were collected from the authors' institutions. The pathology of the SLNs included multilevel hematoxylin and eosin (HE) staining.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

Amyloid deposition of the breast in primary Sjögren syndrome.

We report amyloid deposition in the breast presenting as suspicious microcalcifications on screening mammography. Stereotactic mammotome biopsy provided the diagnosis. The history of the patient revealed primary Sjögren syndrome.

Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation.

Objectives: The aim of this study was to examine the accuracy of the presence of high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow-up cytology and the marginal status of the excised tissue.

Design: Prospective follow-up study.

Setting: Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven.

Comparative expressed sequence hybridization reveals differential gene expression in morphological breast cancer subtypes.

In this study, comparative expressed sequence hybridization (CESH) has been used to compare gene expression patterns in three morphologically different breast cancer subtypes: classic-type invasive lobular carcinoma (ILC), poorly differentiated ERBB2-negative invasive ductal carcinoma-not otherwise specified (IDC-NOS), and poorly differentiated ERBB2-positive IDC-NOS. CESH allows global detection of chromosomal regions with differential gene expression in a way similar to that of comparative genomic hybridization (CGH). Eight cases of each breast cancer subtype were included in the study.

Plasma gelatinase levels in patients with primary breast cancer in relation to axillary lymph node status, Her2/neu expression and other clinicopathological variables.

Matrix metalloproteinases (MMPs), in particular the gelatinases MMP2 and MMP9, are important mediators of tumour invasion and metastasis. We examined whether plasma gelatinase levels could predict lymph node metastasis in breast cancer patients. Further, we investigated the relationship of plasma gelatinase levels with Her2/neu expression, recently acknowledged as an important prognostic factor for recurrence, and with various clinicopathological factors.