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J Thorac Cardiovasc Surg 2001;121:0225-0233
© 2001 The American Association for Thoracic Surgery

General Thoracic Surgery

The {alpha} folate receptor is highly activated in malignant pleural mesothelioma

Raphael Bueno, MDa, Krishnarao Appasani, PhDa, Harriet Mercer, BSa, Susan Lester, MD, PhDb, David Sugarbaker, MDa

From the Division of Thoracic Surgerya and the Department of Pathology,b Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.

This work was partially funded by The Vancouver Foundation and the Brigham Surgical Group Foundation.

Received for publication May 4, 2000. Revisions requested June 12, 2000; revisions received Aug 9, 2000. Accepted for publication Aug 25, 2000. Address for reprints: Raphael Bueno, MD, Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.

Objective: To determine whether the folate receptor gene is overexpressed in malignant pleural mesothelioma.
Methods: Differential display analysis was performed with fresh frozen RNA obtained from normal lung, pleura, and mesothelioma. Sixty differentially expressed genes were identified and characterized. One gene that was over-expressed in mesothelioma versus normal tissue was the human {alpha} folate receptor. In situ hybridization with antisense probes designed on the basis of the sequence of the folate receptor was performed with frozen sections from 61 patients (33 epithelial and 28 mixed or sarcomatoid tumors) with malignant pleural mesothelioma. The controls included normal pleura, normal lung, other cancers, and sense controls for all of the tumors. Northern analysis with a folate receptor probe and immunohistochemical analysis with anti-{alpha} folate receptor antibodies were also performed.
Results: Forty-four (72%) of the 61 mesothelioma tumors were found to have between 2-fold and 4-fold higher mRNA expression of the folate receptor when compared with the control tissues. The histologic type of the tumor did not affect the rate of folate receptor activation. Northern analysis and immunohistochemical experiments confirmed these findings.
Conclusions: A majority of mesothelioma tumors examined overexpress the {alpha} folate receptor protein when compared with normal adjacent tissues. This finding may help explain the observations that antifolate drugs have activity in the treatment of mesothelioma. It also encourages further study of folate receptor–related treatment strategies in this malignancy.






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