Wang, Hanlin L.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

Aims To explore the immunohistochemical utility of proliferating cell nuclear antigen (PCNA), insulin-like growth factor 2 (IGF2) and clusterin in the distinction between malignant and benign liver nodular lesions. Methods Immunohistochemical stains for PCNA, IGF2 and clusterin were performed on 284 liver nodular lesions, including 33 hepatocellular adenomas (HCA), 40 focal nodular hyperplasias (FNH), 77 large regenerative nodules (LRN) and 134 hepatocellular carcinomas (HCC). Results Strong and diffuse nuclear PCNA immunoreactivity was observed in 103 (77%) HCCs but in only 2 (6%) HCAs. None of the FNH and LRN cases showed a strong and diffuse staining pattern. All HCAs, 95% of FNHs and 92% of LRNs showed cytoplasmic IGF2 expression, with a strong staining observed in 70% of HCAs, 20% of FNHs and 30% of LRNs. This was in marked contrast to that observed in HCCs, where 66% of HCCs demonstrated a weak and focal/patchy immunostaining pattern and another 25% showed no detectable IGF2 immunoreactivity. In comparison with their adjacent non-lesional hepatocytes, 75% of HCCs showed decreased IGF2 expression. However, decreased IGF2 expression was not evident in HCAs, FNHs and LRNs. Cytoplasmic staining for clusterin was seen in both benign and malignant nodular lesions. However, an enhanced and exaggerated pericanalicular staining pattern was observed in 75% of HCCs, which was not demonstrated in HCAs, FNHs and LRNs. Conclusions PCNA, IGF2 and clusterin show unique immunostaining characteristics in HCCs, which can be useful adjuncts to other currently available markers to aid in the distinction of HCC from benign liver nodular lesions.