RESUMO
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2-4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus-positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.
RESUMO
PURPOSE: Landmark indicators have not yet to be developed to detect the regression of cervical intraepithelial neoplasia (CIN). We propose that quantitative viral load and indicative histological criteria can be used to differentiate between atypical squamous cells of undetermined significance (ASCUS) and a CIN of grade 1. MATERIALS AND METHODS: We collected 115 tissue biopsies from women who tested positive for the human papilloma virus (HPV). Nine morphological parameters including nuclear size, perinuclear halo, hyperchromasia, typical koilocyte (TK), abortive koilocyte (AK), bi-/multi-nucleation, keratohyaline granules, inflammation, and dyskeratosis were examined for each case. Correlation analyses, cumulative logistic regression, and binary logistic regression were used to determine optimal cut-off values of HPV copy numbers. The parameters TK, perinuclear halo, multi-nucleation, and nuclear size were significantly correlated quantitatively to HPV copy number. RESULTS: An HPV loading number of 58.9 and AK number of 20 were optimal to discriminate between negative and subtle findings in biopsies. An HPV loading number of 271.49 and AK of 20 were optimal for discriminating between equivocal changes and obvious koilocytosis. CONCLUSION: We propose that a squamous epithelial lesion with AK of >20 and quantitative HPV copy number between 58.9-271.49 represents a new spectrum of subtle pathological findings, characterized by AK in ASCUS. This can be described as a distinct entity and called "regressing koilocytosis".