Recent advances in understanding the molecular genetics of common adult tumors have indicated that multiple genetic alterations including the activation of oncogenes and the inactivation of tumor suppressor genes are important in the pathogenesis of these tumors. Loss of heterozygosity is a hallmark of tumor suppressor gene inactivation and has been used to identify chromosomal regions that contain these genes. We have examined allelic loss in the most common tumor in men, prostate cancer. Twenty-eight prostate cancer specimens have been examined for loss of heterozygosity at 11 different chromosomal arms including 3p, 7q, 9q, lOp, lOq, Ulp, 13q, 16p, 16q, 17p, and 18q. Fifty-four percent'(13/24) of clinically localized tumors and 4 of 4 metastatic tumors showed loss of heterozygosity on at least one chromosome. Chromosomes 16q and lOq exhibited the highest frequency of loss of heterozygosity with 30% of tumors showing loss at these chromosomes. These data demonstrate that allelic loss is a common event in prostate cancer and suggest that chromosomes 16q and lOq may contain the sites of tumor suppressor genes important in the pathogenesis of human prostate cancer.

Between 4 and 10% of patients with renal cell carcinoma have tumor involving the inferior vena cava and many of these patients have suprahepatic extension. In patients with intracaval neoplastic extension precise definition of the superior aspect of the tumor thrombus is critical. Transabdominal ultrasonography, computerized tomography (CT), magnetic resonance imaging (MRI) and inferior venacavography are all currently used to evaluate the inferior vena cava in these patients. Intraoperative transesophageal echocardiography was used to image the inferior vena cava in 5 patients with renal cell carcinoma and intracaval neoplastic extension. In each patient transesophageal echocardiography correctly revealed the superior extent of tumor thrombus. In 3 patients tumor thrombus was found at a higher level by transesophageal echocardiography than by CT, MRI and inferior venacavography. In all patients tumor imaging by transesophageal echocardiography correlated well with the gross appearance and extent of tumor found at operation. Echocardiography also documented the absence of residual gross tumor after resection. Transesophageal echocardiography was also useful to assess left ventricular function. Although each of these patients had a pulmonary artery catheter as well transesophageal echocardiography can be useful in situations when right atrial tumor thrombus prevents right heart catheterization. This small series demonstrates that intraoperative transesophageal echocardiography can accurately evaluate the extent of tumor thrombus and provides a means to assess myocardial function complementary to the pulmonary artery catheter.

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To investigate the role of oncogenes in the development of metastatic ability by prostatic cancer, the viral-Harvey-ras (v-H-ras) oncogene was introduced into the Dunning rat prostate adenocarcinoma cell line, AT2.1 by means of DNA transfection. The AT2.1 cell line is a cloned cell line that is anaplastic, rapidly growing, and has low metastatic potential; after subcutaneous (s.c.) inoculation in syngeneic rats, fewer than 10% of inoculated rats develop distant metastases. Calcium phosphate mediated DNA transfections of AT2.1 cells were performed with the v-H-ras oncogene or with control DNA. The in vitro growth rate of cloned transfectants, which contain and express the v-H-ras oncogene is similar to that of untransfected AT2.1 cells and of control transfectants. After s.c. inoculation in syngeneic rats, all transfectants produced rapidly growing tumors with similar growth rates. While control transfectants had low metastatic ability comparable to untransfected AT2.1 cells, the H-ras expressing transfectants metastasized in over 80% of inoculated rats. While the mechanism by which nonmetastatic Dunning tumor sublines spontaneously develop high metastatic ability in vivo during serial s.c. passage has not been addressed in the present studies, these studies do demonstrate that expression of an activated H-ras oncogene can reproducibly convert a tumorigenic nonmetastatic prostatic cell line to a highly metastatic state.