HER2 determination by IHC and FISH correlates with clinical response data in the WO16229 trial with high concordance of IHC and FISH results. Polysomy is the major cause of response in FISH-negative cases; polysomic cases should be retested by strictly standardised IHC.
Germline BRCA1/2 mutations is common in Chinese ovarian cancer patients. This study implies that all ovarian patients should be tested for gBRCAm status regardless of family history and histopathology.
Human epidermal growth factor receptor 2 (HER2) positivity in breast cancer is a prognostic factor regarding tumor aggressiveness and a predictive factor for response to trastuzumab (Herceptin). Early and accurate HER2 testing of all breast cancer patients at primary diagnosis is essential for optimal disease management. Routine HER2 tests, such as immunohistochemistry and fluorescence in situ hybridization (FISH), are subject to interlaboratory variation, and validation by laboratory proficiency testing is important to improve standardization. This study compared immunohistochemistry and FISH testing between five international pathology reference centers. Each center evaluated 20 immunohistochemistry and 20 FISH breast cancer specimens in five testing rounds. In each round, one center selected two sets of four different invasive tumor specimens (set A for immunohistochemistry and set B for FISH) and sent samples to the other four centers in a blinded manner, while retaining samples for its own evaluation. Results were analyzed by an independent coordinator. With immunohistochemistry, there were no differences between the five centers for any of the specimens at the level of diagnostic decision (positive or negative HER2 status). However, differences between laboratories were observed in immunohistochemistry scoring. Of the 20 specimens, four were scored as negative (0/1+) and five as positive (3+) in all centers; eight were negative or equivocal (2+), and three positive or equivocal. After FISH retesting of nine of the 11 equivocal immunohistochemistry cases, consensus was achieved in 15 of 18 (83%) specimens. FISH analysis of set B specimens resulted in consensus between centers in 16 of 20 (80%) specimens (six negative and 10 positive). All four discordant FISH specimens were scored as having HER2:CEP17 ratios within the range 1.7-2.3 by at least one center. Equivocal immunohistochemistry and borderline FISH cases are difficult to interpret, even for highly experienced and validated laboratories, highlighting the need for quality-control procedures.
Multilocus enzyme electrophoresis has shown that a collection of I 0 1 arginine-, hypoxanthine-, uracil-requiring (AHU') isolates of Neisseria gonorrhoeae, recovered over a 39 year period from the UK and Denmark, were of a single electrophoretic type (91 O/ O of strains), or differed from the predominant electrophoretic type at only a single locus. The striking uniformity of the AHU' isolates, and the correlation between auxotype, serovar and overall genetic background, contrasts with previous studies of gonococcal populations (that included very few AHU' strains), and a small sample of non-AHU' isolates studied here, which demonstrated a non-clonal population structure and a lack of association between auxotype, serovar and genetic background. There was no marked difference in the ability of AHU' isolates to be transformed with their own DNA, or with DNA from gonococci of other auxotypes, and the relative genetic stability of AHU' isolates does not appear to be due to a defect in their ability to be transformed. An alternative possibility is that AHU' gonococci recombine with other lineages, but that the resulting recombinants are not maintained in the population. This would occur, for example, if AHU' gonococci competed poorly in mixed infections, within which effective recombination between lineages occurs, and are usually only transmitted from individuals who are singly infected with an AHU' strain. The association between AHU' gonococci and asymptomatic infections may lead to an increased rate of transmission of these strains which under this scenario would be needed to prevent them from being lost from the population.
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