ABSTRACT
BACKGROUND: The gold standard of HER2 status assessment in breast cancer is still debated. Immunohistochemistry (IHC) and in-situ technology as fluorescent-labeled methodology (FISH) can be influenced by pre-analytical factors, assay-conditions and interpretation of test results. We retrospectively conducted this quality control study and analyzed HER2 test results in breast cancer within the routine diagnostic service in a single institution over a period of 12 years. We addressed the question how stable and concordant IHC and FISH methods are and whether HER2 positivity rate has changed over this period. METHODS: Data of 7714 consecutive HER2-FISH-assays in a period of 12 years (2001-2012) on breast cancer biopsies and excision specimens were retrospectively analyzed. From 2001 to 2004, FISH tests were performed from all cases with IHC score 3+ and 2+ (and in some tumors with IHC score 1+ and 0). From 2005-2010, HER2 status was only determined by FISH. From 2011-2012, all breast carcinomas were analyzed by both IHC and FISH. Scoring and cut-off-definition were done according to time-current ASCO-CAP and FDA-guidelines. RESULTS: Between 2001-2004, IHC score 3+ was diagnosed in 22% of cases, 69% of these 3+ cases were amplified by FISH. 6% of IHC score 0/1+ cases were amplified by FISH. There was a mean amplification rate of 15.8% (range 13 -19%) using FISH only HER2-assays (2005-2010). Starting 2008, a slight drop in the amplification rate from 17% to 14% was noticed due to the modified ASCO-criteria in 2007. From 2011-2012, 12% of cases were 3+ by IHC, 84% of them were amplified by FISH. Less than 1% of IHC score 0/1+ cases were amplified by FISH. Concordance between FISH and IHC increased from 83% to 97%. CONCLUSIONS: Our quality control study demonstrates that HER2 positivity rate remained stable by FISH-technology but showed a significant variation by IHC over the analyzed 12 years. Improvement in concordance rate was due to standardization of pre-analytical factors, scoring and interpretation.
Subject(s)
Breast Neoplasms/genetics , Receptor, ErbB-2/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Quality Control , Receptor, ErbB-2/metabolism , Reproducibility of Results , Retrospective Studies , Sensitivity and SpecificityABSTRACT
BACKGROUND: Pathologists are highly trained medical professionals who play an essential part in the diagnosis and therapy planning of malignancies and inflammatory diseases. Their work is associated with potential health hazards including injuries involving infectious human tissue, chemicals which are assumed to be carcinogenic or long periods of microscope and computer work. This study aimed to provide the first comprehensive assessment of the health situation of pathologists in Switzerland. METHODS: Pathologists in Switzerland were contacted via the Swiss Society of Pathologists and asked to answer an ethically approved, online anonymous questionnaire comprising 48 questions on occupational health problems, workplace characteristics and health behaviour. RESULTS: 163 pathologists participated in the study. Forty percent of pathologists reported musculoskeletal problems in the previous month. The overall prevalence was 76%. Almost 90% of pathologists had visual refraction errors, mainly myopia. 83% of pathologists had experienced occupational injuries, mostly cutting injuries, in their professional career; more than one fifth of participants reported cutting injuries in the last year. However, long lasting injuries and infectious diseases were rare. Depression and burnout affected every eighth pathologist. The prevalence of smoking was substantially below that of the general Swiss population. CONCLUSIONS: The results of this study suggest that more care should be taken in technical and personal protective measures, ergonomic workplace optimisation and reduction of work overload and work inefficiencies. Despite the described health risks, Swiss pathologists were optimistic about their future and their working situation. The high rate of ametropia and psychological problems warrants further study.
Subject(s)
Health Behavior , Health Status Indicators , Musculoskeletal Diseases/complications , Pathology , Adult , Burnout, Professional/epidemiology , Cohort Studies , Female , Humans , Male , Middle Aged , Musculoskeletal Diseases/epidemiology , Occupational Diseases , Occupational Exposure/statistics & numerical data , Risk Factors , Self Report , Surveys and Questionnaires , Switzerland/epidemiology , Workforce , Workplace/statistics & numerical data , Wounds and Injuries/epidemiologyABSTRACT
The HER2 amplicon on chromosome 17q is variable in size and occasionally includes Topoisomerase 2A (TOP2A) at 17q21-22. It has been suggested that TOP2 co-amplification, not HER2 amplification on chromosome 17q11.2-12, is a useful predictive marker of response to anthracycline-based chemotherapy in breast cancer patients. Given the significant toxicities of anthracyclines, the detection methods of TOP2A gene amplifications have to be standardized. We determined TOP2A gene alterations using two different fluorescence in situ hybridization (FISH) DNA probes. HER2 amplifications were identified with the PathVysion probe. TOP2A status of 42 HER2 amplified breast cancers was tested by FISH with PathVysion covering 160 kb and DAKO pharm DX covering 228 kb of the TOP2A amplicon. TOP2A protein expression was tested by immunohistochemistry. Multiplex-ligation dependent probe amplification (MLPA) was performed retrospectively in cases showing discrepancies. TOP2A was amplified in 15 of 42 cases (35%) with DAKO pharm DX and in 11 of 42 cases (26%) with PathVysion. In all four discrepant cases, MLPA showed no TOP2A amplification, but instead amplification of an upstream region including HER2. TOP2A was deleted in the same seven of 42 carcinomas (17%) with both probes. TOP2A protein expression was detected in all 42 tumours (100%) with high intratumoral heterogeneity. TOP2A amplification rate depends on the length of the hybridized probes for the TOP2A locus. Because TOP2A, not HER2, is a target of anthracyclines, non-overlapping DNA probes should be used to evaluate any associations between such alterations and response to anthracycline-based chemotherapy.
Subject(s)
Antigens, Neoplasm/genetics , Breast Neoplasms/genetics , DNA Probes , DNA Topoisomerases, Type II/genetics , DNA-Binding Proteins/genetics , Gene Amplification , In Situ Hybridization, Fluorescence , Antigens, Neoplasm/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , DNA Topoisomerases, Type II/metabolism , DNA-Binding Proteins/metabolism , Female , Gene Dosage , Humans , Poly-ADP-Ribose Binding Proteins , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolismABSTRACT
F-18 fluorodeoxyglucose (FDG)-PET-CT is increasingly used in the management of patients with ovarian cancer. However, there is a considerable overlap in the imaging features of malignant and benign ovarian lesions because physiological FDG-uptake in the ovaries can occur, depending on the menstrual cycle in premenopausal women.We present a case of FDG uptake in the ovary co-occurring with an intensely FDG active tumor of the abdominal wall in a 44-year-old woman. PET-CT findings, together with medical history, raised the suspicion for a metastasizing ovarian cancer. However, histologic examination demonstrated benign findings, namely abdominal wall leiomyoma and an ovarian follicular cyst.
