Glypican-1 Expression in Epithelioid Mesothelioma, Adenocarcinoma and SCC of the Lung

Lung carcinoma is the second most common cancer and a leading cause of cancer-related mortality worldwide, comprising almost 20% of all cancer deaths. In Egypt, lung carcinoma ranks the 5th among all cancer cases. It is more common in males than females, and most people diagnosed at the age of 65 years or older. The main risk factor of lung malignancy is tobacco smoking.

There are two main histologic variants of lung carcinoma, non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). NSCLC represents more than 80% of all lung carcinomas. Histologically, NSCLC is divided into adenocarcinoma, squamous cell carcinoma (SCC) and large cell carcinoma; of which lung adenocarcinoma is the most common subtype representing about 40%. Specific therapies can be offered to patients based on the histological and molecular status of primary tumors. Therefore, an accurate differentiation between solid predominant lung adenocarcinoma and poorly differentiated lung SCC has become increasingly indispensable; the accurate discrimination of these two main histological types is required for gene-targeted therapy.

Malignant mesothelioma is an aggressive neoplasm that arises from mesothelial cells which form the lining of the pleural, pericardial, and peritoneal cavities. Majority of malignant mesothelioma, approximately 85%, occur in pleural cavity and most of the remainder arising in the peritoneum. In the United States around 3,000 new cases are diagnosed each year. In Egypt, pleural malignant tumors formed 1.3% of total malignant tumors. Pleural mesothelioma is the most frequent primary pleural malignant tumor forming more than half of the cases. The main risk factor for pleural mesothelioma is exposure to asbestos. Other risk factors may include; radiation exposure, old age, male gender and exposure to certain other minerals.

Malignant mesothelioma is divided into three histologic variants that include: epithelioid, sarcomatoid and biphasic variants. Epithelioid variant is the most common subtype representing 70% of malignant mesothelioma. There is a strong resemblance between epithelioid mesothelioma and lung adenocarcinoma, some of peripheral lung adenocarcinoma or SCC present with pleurotropic growth like mesothelioma. The prognosis and management of epithelioid mesothelioma differ from lung carcinoma, so accurate diagnosis of mesothelioma is necessary.

Glypican-1 (GPC1) is one the six glypican family members. It is one of cell surface heparan sulfate proteoglycans that acts as a growth factor signaling. It plays role in the control of cell division and growth regulation. It is encoded by GPC1 gene located at 2q37. It contains 588 amino acids with three predicted heparan sulfate chains. It has been evaluated as a potential target for cancer therapy. Many studies have shown that GPC1 is crucial for efficient cancer cell growth, metastasis and angiogenesis. Glypican-1 overexpression has previously been reported in breast cancer, pancreatic cancer and glioma.

Studies evaluating the expression of Glypican-1 in pleural mesothelioma and lung carcinoma are deficient. Knowledge about its potential value in differentiation between pleural epithelioid mesothelioma, lung adenocarcinoma and SCC needs further elucidation.

Aim of This Work:

The aim of this study is to evaluate the immunohistochemical expression of Glypican-1 in pleural epitheloid mesothelioma, lung adenocarcinoma and lung SCC, and to correlate its expression with some known clinico-pathological parameters, to evaluate its diagnostic and prognostic role.