Expression of ras oncogene p21 in prostate cancer.

The major neoplastic transformation-inducing genes of human solid tumors are members of the ras oncogene family. We used an immunohistochemical assay to assess expression of both the unaltered and the mutated ras oncogene protein (p21) in normal and neoplastic prostatic cells. With the concentration of monoclonal antibody used in this study, epithelial and stromal cells from subjects with normal prostates and from 19 patients with benign prostatic hyperplasia were negative for p21 antigen. This antigen was detected in 2 of 6 prostates with Grade I carcinoma, 4 of 6 with Grade II, and all of 17 with higher grades. A semiquantitative immunohistochemical method demonstrated that expression of the p21 antigen in a carcinoma strongly correlated with nuclear anaplasia and was inversely related to the degree of glandular differentiation. However, markedly anaplastic tumors were often more heterogeneous in expression of p21 and contained areas of low staining for the antigen. Comparison of p21 antigen with tumor carcinoembryonic antigen and prostate-specific antigen demonstrated that ras p21 was the only phenotypic marker that correlated with histologic tumor grade. Thus, ras oncogene p21 may represent a new class of biologically relevant tumor markers and may be a useful adjunct to histopathologic examination in determining the prognosis of patients with prostate cancer.

[1]  J. Bailar,et al.  The histology and prognosis of prostatic cancer. , 1967, The Journal of urology.

[2]  G. Murphy,et al.  Carcinoembryonic antigen in patients with tumors of the urogenital tract , 1972, Cancer.

[3]  A. Lilienfeld,et al.  Relation between benign prostatic hyperplasia and cancer of the prostate. A prospective and retrospective study. , 1974, Lancet.

[4]  G. Murphy,et al.  Prostatic carcinoma. relationship between primary tumor, histologic grade, and response to chemotherapy. , 1976, Urology.

[5]  S. Hsu,et al.  Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. , 1981, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[6]  Relationship between prostatic cytoplasmic and nuclear androgen receptors in patients with carcinoma of the prostate. , 1981, European urology.

[7]  J. Pontes,et al.  Immunofluorescence for prostatic acid phosphatase: clinical applications. , 1981, The Journal of urology.

[8]  G. Murphy,et al.  Prostatic‐specific antigen: An immunohistologic marker for prostatic neoplasms , 1981, Cancer.

[9]  Kenji Shimizu,et al.  Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change , 1982, Nature.

[10]  M. Barbacid,et al.  Oncogenes in solid human tumours , 1982, Nature.

[11]  Eugenio Santos,et al.  A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene , 1982, Nature.

[12]  Cori Bargmann,et al.  Mechanism of activation of a human oncogene , 1982, Nature.

[13]  E. Scolnick,et al.  Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family , 1982, Journal of virology.

[14]  C. Der,et al.  Altered gene products are associated with activation of cellular rasK genes in human lung and colon carcinomas , 1983, Cell.

[15]  J. Bishop.  Cellular oncogenes and retroviruses. , 1983, Annual review of biochemistry.

[16]  G. Prout,et al.  Evaluation of prostate specific acid phosphatase and prostate specific antigen in identification of prostatic cancer. , 1983, The Journal of urology.

[17]  P. Hand,et al.  Differential binding to human mammary and nonmammary tumors of monoclonal antibodies reactive with carcinoembryonic antigen. , 1983, Cancer Investigation.

[18]  R. Weinberg,et al.  Cellular oncogenes and multistep carcinogenesis. , 1983, Science.

[19]  A. Ng,et al.  Multiple immunoperoxidase markers in benign hyperplasia and adenocarcinoma of the prostate. , 1984, American journal of clinical pathology.

[20]  P. Hand,et al.  Monoclonal antibodies of predefined specificity detect activated ras gene expression in human mammary and colon carcinomas. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[21]  D. Spandidos,et al.  Malignant transformation of early passage rodent cells by a single mutated human oncogene , 1984, Nature.

[22]  J. Feramisco,et al.  Microinjection of the oncogene form of the human H-ras (t-24) protein results in rapid proliferation of quiescent cells , 1984, Cell.

[23]  P. Hand,et al.  Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases , 1984, Nature.

[24]  I. Verma,et al.  Expression of cellular oncogenes in human malignancies. , 1984, Science.

[25]  M. Barbacid,et al.  Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient. , 1984, Science.

[26]  R. Kurzrock,et al.  Expression of p21ras in fresh primary and metastatic human colorectal tumors. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Viola,et al.  ras Oncogene p21 expression is increased in premalignant lesions and high grade bladder carcinoma , 1985, The Journal of experimental medicine.

[28]  Mark R. Smith,et al.  Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells , 1985, Nature.

[29]  J. Rhim,et al.  Frequency of molecular alterations affecting ras protooncogenes in human urinary tract tumors. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[30]  F. Sinowatz,et al.  A histochemical study of glycosidases in benign prostatic hyperplasia and in prostatic carcinoma in the human , 2004, Urological Research.