Amy Ziober

Lab-On-A-Chip for Oral Cancer Screening and Diagnosis

Oral squamous cell carcinoma (OSCC) is a disfiguring and deadly cancer. Despite advances in therapy, many patients continue to face a poor prognosis. Early detection is an important factor in determining the survival of patients with OSCC. No accurate, cost‐efficient, and reproducible method exists to screen patients for OSCC. As a result, many patients are diagnosed at advanced stages of the disease. Early detection would identify patients, facilitating timely treatment and close monitoring. Mass screening requires a rapid oral cancer diagnostic test that can be used in a clinical setting. Current diagnostic techniques for OSCC require modern laboratory facilities, sophisticated equipment, and elaborate and lengthy processing by skilled personnel. The lab‐on‐chip technology holds the promise of replacing these techniques with miniaturized, integrated, automated, inexpensive diagnostic devices. This article describes lab‐on‐chip devices for biomarker‐based identification of oral cancer. Similar methods can be employed for the screening of other types of cancers.

The extracellular matrix in oral squamous cell carcinoma: Friend or foe?

Oral squamous cell carcinoma is a disfiguring, highly invasive and metastatic cancer. Despite advances in detection and therapy, many patients will continue to face a poor prognosis. It is well established that the predominate factor determining overall survival in patients with oral squamous cell carcinoma is lymph node involvement. Tumor growth and progression to invasive cancer requires tumor cell interactions with the extracellular matrix. An understanding of how the extracellular matrix influences tumor development and invasion is fundamental in the development of new prognostic indicators and treatment strategies for oral squamous cell carcinoma. In this review, we summarize how changes in the extracellular matrix contribute to oral cancer development.

Transoral robotic surgery and adjuvant therapy for oropharyngeal carcinomas and the influence of p16INK4a on treatment outcomes

To determine the prognostic influence of p16INK4a immunohistochemistry on the survival of resectable oropharyngeal carcinomas (OPSCC).

Tumor Deposition of Laminin‐5 and the Relationship With Perineural Invasion

Objectives/Hypothesis Perineural invasion (PNI) is increasingly being recognized as an important indicator of aggressiveness in head and neck squamous cell carcinoma. The mechanisms of PNI are poorly understood. Laminin‐5, an important basement membrane constituent, has been shown to be essential in head and neck squamous cell carcinoma invasion and motility. We hypothesized that tumors exhibiting increased expression of laminin‐5 are more likely to be neurotropic.

Integrins in head and neck squamous cell carcinoma invasion

Objective To relate the invasive properties of different squamous cell cancer cell lines to the function and expression of the integrins.

Dysregulation of Hypoxia Inducible Factor-1α in Head and Neck Squamous Cell Carcinoma Cell Lines Correlates With Invasive Potential†

Objectives/Hypothesis Tumor hypoxia appears to be closely associated with tumor propagation, malignant progression, and resistance to radiotherapy. Hypoxia inducible factor‐1α (HIF‐1α) is a transcription factor that is upregulated under hypoxic conditions and activates hypoxic adaptation pathways which include neovascularization, erythropoiesis, and glycolysis. Hypoxia inducible factor‐1α is under tight regulation with undetectable levels of expression in normoxia and robust expression in hypoxia. Mutations that activate oncogenes or inactivate tumor suppressor genes increase the expression of HIF‐1α. Furthermore, it has been demonstrated that HIF‐1α is overexpressed in head and neck squamous cell carcinoma and that the degree of expression has predictive and prognostic significance for patients undergoing radiotherapy. The study investigated whether overexpression of HIF‐1α in head and neck squamous cell carcinoma results from a physiological response to local hypoxia or from oncogenic mutational progression.

Role of carbonic anhydrase IX, α-methylacyl coenzyme a racemase, cytokeratin 7, and galectin-3 in the evaluation of renal neoplasms: a tissue microarray immunohistochemical study

Kidney tumors of various types may behave differently and have different prognosis. Because of some overlapping morphological features and immunohistochemical staining pattern, they may pose diagnostic challenge. Therefore, it is necessary to explore additional immunohistochemical stains to help classifying these epithelial neoplasms. Tissue microarrays of 20 cases each of renal cell carcinomas of clear cell, chromophobe, and papillary variants and oncocytoma were constructed and used to test a panel of immunohistochemical markers including carbonic anhydrase IX, galectin-3, cytokeratin 7 (CK7), and α-methylacyl coenzyme a racemase. Carbonic anhydrase IX was highly sensitive for clear cell renal cell carcinoma (90% positivity) and was negative in all other renal epithelial tumors except for 1 chromophobe renal cell carcinoma (chRCC). Expression of galectin-3 was found mostly in renal tumors with oncocytic features, including oncocytomas (100%) and chRCCs (89%). α-Methylacyl coenzyme a racemase was positive in papillary renal cell carcinoma (100%). CK7 was positive in papillary renal cell carcinoma (90%), chRCC (89%), and oncocytoma (90%). Although both chRCC and oncocytoma were positive for CK7, but with a different patterns, CK7 staining in chRCC was diffuse, whereas it was sporadic in oncocytoma. Panel of carbonic anhydrase IX, galectin-3, CK7, and α-methylacyl coenzyme a racemase is sensitive and specific for the differential diagnosis of the renal epithelial tumors.

Overcoming the Immunosuppressive Tumor Microenvironment of Hodgkin Lymphoma Using Chimeric Antigen Receptor T Cells

Patients with otherwise treatment-resistant Hodgkin lymphoma could benefit from chimeric antigen receptor T-cell (CART) therapy. However, Hodgkin lymphoma lacks CD19 and contains a highly immunosuppressive tumor microenvironment (TME). We hypothesized that in Hodgkin lymphoma, CART should target both malignant cells and the TME. We demonstrated CD123 on both Hodgkin lymphoma cells and TME, including tumor-associated macrophages (TAM). In vitro, Hodgkin lymphoma cells convert macrophages toward immunosuppressive TAMs that inhibit T-cell proliferation. In contrast, anti-CD123 CART recognized and killed TAMs, thus overcoming immunosuppression. Finally, we showed in immunodeficient mouse models that CART123 eradicated Hodgkin lymphoma and established long-term immune memory. A novel platform that targets malignant cells and the microenvironment may be needed to successfully treat malignancies with an immunosuppressive milieu.Significance: Anti-CD123 chimeric antigen receptor T cells target both the malignant cells and TAMs in Hodgkin lymphoma, thereby eliminating an important immunosuppressive component of the tumor microenvironment. Cancer Discov; 7(10); 1154-67. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047.

A case of primary clear cell hepatocellular carcinoma in a non-cirrhotic liver: an immunohistochemical and ultrastructural study.

The clear cell variant of hepatocellular carcinoma is a rare entity, occurring at a frequency of less than 10% of hepatocellular carcinoma, with a female prevalence and usually associated with hepatitis C and cirrhosis. We reported a case of primary clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without history of hepatitis. Our examination included gross pathology, histopathology, immunohistochemistry, special stains, and electron microscopy evaluation. The tumor was composed of sheets of medium-to-large cells with foamy and reticulated cytoplasm and small-to-medium sized nuclei with variably prominent nucleoli. Oil red O stain showed abundant intracellular lipid. Periodic Acid-Schiff stain confirmed the presence of abundant glycogen deposition. Immunohistochemically the tumor cells were positive for Hep Par1, negative for epithelial membrane antigen, steroidogenic factor-1, HMB45, melan A, CK7 and CK20. Electron microscopy study was performed, which was first done in a clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without elevation of liver function tests. Ultrastructural evaluation of the clear cells showed scarce cellular organelles, cytoplasmic lipid vacuoles and swollen mitochondria.

Useful immunohistochemical panel for differentiating clear cell papillary renal cell carcinoma from its mimics

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described low-grade renal cell tumor. In this study, we investigated the expression of paired box 8 (PAX-8), carbonic anhydrase IX (CA IX), CK7, and α-methylacyl-CoA-racemase (AMACR) in this tumor by immunohistochemistry in a group of 20 cases of CCPRCC. Clear cell papillary renal cell carcinoma showed diffuse (70%) or intermediate (30%) nuclear positivity for PAX-8 in each case, with predominantly moderate intensity (50%). Ninety percent of the cases showed some degree of cytoplasmic staining for CA IX, predominantly with moderate intensity (50%). In addition, each case of CCPRCC also showed diffuse membranous staining for CK7. Most CCPRCCs (95%) were negative for AMACR. PAX-8, CA IX, CK7, and AMACR comprise a concise panel for distinguishing CCPRCC from its mimics. PAX-8 positivity helps to confirm the renal origin of this tumor. Positivity for CA IX and CK7 differentiate CCPRCC from conventional clear cell renal cell carcinoma, which is usually CA IX positive while CK7 negative. The CK7-positive and AMACR-negative pattern seen in CCPRCC differentiates it from papillary renal cell carcinoma, which is usually positive for both AMACR and CK7.