Glutamine Synthetase Immunoreactivity in Peritumoral Hyperplasia in Liver: Case Report of a Metastatic Paraganglioma With Focal Nodular Hyperplasia-Like Changes and Review of an Additional 54 Liver Masses.

Objectives: Focal nodular hyperplasia (FNH) and peritumoral hyperplasia in the liver exhibit increased immunoreactivity for glutamine synthetase (GS). We observed FNH-like changes with map-like GS staining surrounding a metastatic paraganglioma and sought to determine how often such changes occur around primary and metastatic liver lesions.

Methods: We performed GS immunohistochemistry in liver cases of 20 metastatic neuroendocrine carcinomas (NECs), 21 metastatic colon carcinomas (CCs), seven hepatocellular carcinomas (HCCs), and six FNHs and assessed lesions for size, degree of fibrosis (scored 1-3), and peritumoral hyperplasia.

An update on clinicopathological, immunohistochemical, and molecular profiles of colloid carcinoma of the lung.

Colloid carcinoma is a rare subtype of lung adenocarcinoma characterized by abundant pools of extracellular mucin and scant malignant epithelium. Because of the rarity of these tumors, many of the reported clinicopathological and immunohistochemical characteristics are contradictory. Moreover, the molecular alterations that underlie these tumors are unknown.

Stemness characteristics of fibrolamellar hepatocellular carcinoma: immunohistochemical analysis with comparisons to conventional hepatocellular carcinoma.

The involvement of cancer stem cells (CSC) in tumorigenesis has been studied in several malignancies, but their presence in fibrolamellar hepatocellular carcinoma (FLHCC) has not previously been evaluated. General characteristics of "stemness" include the expression of putative stem cell antigens, reduced cell cycle progression, and limited functional differentiation or dedifferentiation under the influence of the microenvironment. Immunohistochemical probes applied to 8 archival cases of FLHCC vis-à-vis contiguous non-neoplastic parenchyma, which was present in 5 cases, revealed such stemness characteristics by showing: (a) stem cell antigens, with moderate to intense expression of CD133 in the cytoplasm (6 of 8 FLHCC cases and comprising >40% of the tumoral areas) and of CD44 on the plasmalemmal aspect (7 of 8 FLHCC cases and comprising 50 to 95% of the tumor cells), vs foci of such overexpressions in only 1 of 5 of the contiguous liver parenchyma (p = 0.

Constitutive activation of nuclear factor-kappa B (NF-kB) signaling pathway in fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLHCC) is an aggressive neoplasm due to high frequency of recurrence after surgical resection and resistance to chemotherapy and radiation therapy. Activation of transcription factor NF-kB signaling pathway has been recognized for involvement in progression of various malignant neoplasms. The role of NF-kB pathway in FLHCC has not been studied to date.

Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in Ewing family of tumors.

In 3 patients with the Ewing family of tumors (EFT), morphoproteomic analyses of the tumors revealed constitutive activation of the mTOR, ERK, and NF-kappaB pathways, as evidenced by: (a) expression of phosphorylated (p)-mTOR, p-p70S6K, p-ERK 1/2, and p-NF-kappaB proteins using phosphospecific immunohistochemical probes directed against the activation sites; (b) nuclear translocation of p-p70S6K, p-ERK 1/2, and p-NF-kappaB p65; and (c) correlative expression of Ki-67 and Skp2 proteins consistent with cell cycling consequent to signal transduction by these pathways of convergence. This study examines the cytogenetic and molecular correlates and provides insight into therapeutic strategies relevant to this morphoproteomic profile. Based on a literature review, these observations appear to be the first morphoproteomic study of such pathways of convergence in tumors from EFT patients.