Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?
ENDOCRINE PATHOLOGY
Authors: Fukuhara, Noriaki; Iwata, Takeo; Inoshita, Naoko; Yoshimoto, Katsuhiko; Kitagawa, Masanobu; Fukuhara, Hirokazu; Tatsushima, Keita; Yamaguchi-Okada, Mitsuo; Takeshita, Akira; Ito, Junko; Takeuchi, Yasuhiro; Yamada, Shozo; Nishioka, Hiroshi
Abstract
Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP).CTNNB1(beta-catenin) mutations are detected in ACPs, and theBRAFV600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear beta-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining, and one PCP showed membranous beta-catenin expression and negative BRAF V600E immunostaining. Among the 26 nuclear beta-catenin expression cases, 11 hadCTNNB1mutations; however, 15 cases had mutations of neitherCTNNB1norBRAFV600E. All 11 BRAF V600E immunopositive cases hadBRAFV600E mutations. When comparing clinical features, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear beta-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice.
Harmonization of Molecular Testing for Non-Small Cell Lung Cancer: Emphasis on PD-L1
FRONTIERS IN ONCOLOGY
Authors: Imyanitov, Evgeny N.; Ivantsov, Alexandr O.; Tsimafeyeu, Ilya, V
Abstract
Comprehensive molecular testing plays a critical role in the choice of treatment for non-small lung cell cancer (NSCLC). The analysis of druggable alterations in EGFR, BRAF, MET, KRAS, ALK, ROS1, RET and NTRK1/2/3 genes is more or less standardized and can be achieved using a single diagnostic platform, e.g., next generation sequencing (NGS) or polymerase chain reaction (PCR). In contrast to above targets, PD-L1 testing requires the use of immunohistochemistry (IHC). There are multiple PD-L1 IHC assays, which utilize distinct antibodies and detection systems. These PD-L1 tests are tailored to distinct drugs, often rely on different thresholds and scoring guidelines, and are characterized by incomplete inter-laboratory and inter-observer reproducibility. Several studies evaluated the performance of PD-L1 RNA expression tests, as PCR-based RNA analysis is compatible with other NSCLC molecular testing platforms, can be performed in a semi-automated manner, and has a potential for proper standardization. These investigations revealed a correlation between PD-L1 protein and RNA expression; however, there were NSCLCs demonstrating decent amounts of PD-L1 transcript in the absence of PD-L1 IHC staining. Clinical studies are required to evaluate, which of the two PD-L1 testing approaches, i.e., RNA or protein expression measurement, has a better predictive value.