Differentiated thyroid tumors (DTTs) are characterized by significant molecular variability in both spatial and temporal intra-tumoral heterogeneity (ITH), that could influence the therapeutic management. ITH phenomenon appears to have a relevant role in tumor growth, aggressive behavior and drug resistance. Accordingly, characteristics and consequences of ITH in DTTs should be better analyzed and understood in order to guide clinical practice, improving survival. Consequently, in the present review, we investigated morphological and molecular ITH of DTTs in benign, borderline neoplasms and in malignant entities, summarizing the most significant data. Molecular testing in DTTs documents a high risk for recurrence of cancer associated with BRAFV600E, RET/PTC 1/3, ALK and NTRK fusions, while the intermediate risk may be related to BRAFK601E, H/K/N RAS and PAX8/PPARγ. In addition, it may be suggested that tumor genotype is associated with peculiar phenotype.
Human epidermal growth factor receptor-2 (HER2)-expression gastro-oesophageal adenocarcinomas (GEA) gained interest as an important target for therapy with trastuzumab. In the current review, we focused the current knowledge on HER2 status in dysplastic and neoplastic gastric conditions, analyzing the methodological procedures to identify HER2 expression/amplification, as well as the proposed scoring recommendations. One of the most relevant questions to evaluate the useful impact of HER2 status on therapeutic choice in GEAs is represented by the significant heterogeneity of HER2 protein and gene expression that may affect the targeted treatment selection. Future development of biotechnology will continue to evolve in order to offer more powerful detection systems for the assessment of HER2 status. Finally, liquid biopsy as well as mutation/amplification of several additional genes may furnish an early detection of secondary HER2 resistance mechanisms in GEAs with a better monitoring of the treatment response.
Background:
The immunohistochemical analysis of autophagy-related
proteins (ATGs) has been recently applied in human pathology to study differentiation
and cancer progression. The aim of the present study is to analyze a cohort of gastric
carcinomas (GC) by five ATG antisera (Beclin-1, LC3A/B, p62, ULK-1 and AMBRA-1),
also evaluating their possible relationship with clinicopathological parameters, HER2
status and final outcome of patients.
Methods:
A cohort of 123 GCs has been studied by ATG antisera utilizing Masuda's
criteria that define positive cases in which at least two out of five protein expressions
were documented.
Results:
The immunohistochemical signature for autophagy (A-IHC) was 49.59% as a
whole. The percentage of A-IHC ranged from 31% for poorly cohesive carcinomas to
56% for adenocarcinomas. The performance of each ATG immunomarker documented
high values for sensitivity, specificity and efficiency for LC3A/B, Beclin-1 and p62. In
univariate analysis of GC, grade, stage, Ki67 expression, HER2 status as well as A-IHC
appeared as emerged as relevant parameters with a high p-value (p < 0.001). Finally, in
multivariate analysis, HER2 status, stage and A-IHC emerged as independent
prognostic variables. In the comparison of survival curves, GC cases immunoreactive for
A-IHC exhibited a shorter survival with a worse outcome.
Conclusions:
We have hypothesized that A-IHC could represent an additional
morphological tool to provide prognostic elements in order to identify patients affected by
aggressive with shorter survival and worse outcome.
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